{"id":60927,"date":"2023-09-12T11:12:01","date_gmt":"2023-09-12T10:12:01","guid":{"rendered":"https:\/\/touchendocrinology.com\/?p=60927"},"modified":"2023-11-20T16:01:25","modified_gmt":"2023-11-20T16:01:25","slug":"are-prepubertal-gynaecomastia-and-premature-thelarche-linked-to-topical-lavender-and-tea-tree-oil-use","status":"publish","type":"post","link":"https:\/\/touchendocrinology.com\/pediatric-endocrinology\/journal-articles\/are-prepubertal-gynaecomastia-and-premature-thelarche-linked-to-topical-lavender-and-tea-tree-oil-use\/","title":{"rendered":"Are Prepubertal Gynaecomastia and Premature Thelarche Linked to Topical Lavender and Tea Tree Oil Use?"},"content":{"rendered":"<h1 id=\"ae5257bc-ad66-4274-971a-bf4fe3c494bd\" class=\"jrnlHead1\">Article highlights<\/h1>\n<ul id=\"f189f210-ddae-414c-9637-16056fcb0b81\">\n<li id=\"e96c57e9-71d3-4bdf-84fe-41df9c36f416\">\n<p id=\"8a38cc11-b9c3-40ff-bc82-b9de1a203845\" class=\"jrnlListPara\">Lavender and tree tea oils have\u00a0<em id=\"b94ef17c-dc4c-4c1d-ba6e-ce3cf02c8ec2\" class=\"sty cts-3\">in vitro<\/em>\u00a0oestrogenic and antiandrogenic activity.<\/p>\n<\/li>\n<li id=\"6b145759-83d9-414a-9b5a-2507b77ddbf2\">\n<p id=\"c5b1c415-9f07-4198-9de5-9afb32696d4a\" class=\"jrnlListPara\">It has been postulated that these oils may cause prepubertal gynaecomastia and premature thelarche.<\/p>\n<\/li>\n<li id=\"0bff33ef-7869-4887-aa9a-12a864947980\">\n<p id=\"16bd631e-c1dd-4f62-aab4-48a16e9e7f49\" class=\"jrnlListPara\">The association is based on a small number patients (N=12) described in five publications.<\/p>\n<\/li>\n<li id=\"688e1865-bd90-45d6-b4b6-1f0dc1a353cd\">\n<p id=\"de72fb54-f39f-407a-8deb-1381ea49ce61\" class=\"jrnlListPara\">Based upon the amount of dermal penetration of the oils or their constituents and the amount of these oils that would have to be applied for a long duration, it is unlikely that there is sufficient absorption to cause premature breast enlargement.<\/p>\n<\/li>\n<li id=\"f76dd2b7-8259-4ef7-86ac-6db1877ca5b7\">\n<p id=\"89666629-2709-40c7-96e9-a5a04a2617df\" class=\"jrnlListPara\">Using Hill\u2019s criteria for evidence of causation, we conclude that the strength of association between these essential oils and premature breast development is weak, and that a cause-and-effect association has not been shown.<\/p>\n<\/li>\n<\/ul>\n<p id=\"88eaa546-c756-4dc1-8a6c-9faa44c99c34\" class=\"jrnlSecPara\">In 2007, Henley and colleagues proposed a link between the use of both lavender oil (LO) and tea tree oil (TTO) and the development of prepubertal gynaecomastia in three boys. They demonstrated that LO and TTO had oestrogen agonist and androgen antagonist activity\u00a0<em id=\"0b42fb62-7f96-4daf-93b3-59b98def0432\">in vitro,<\/em>\u00a0suggesting that LO and TTO were endocrine disrupting chemicals.<span id=\"93341e65-d04a-46a5-abba-92ccb648099e\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"b54ab9cc-1db9-43aa-8e68-d74fc5b05195\">1<\/sup><\/span>\u00a0Subsequently, Ramsey et al. extended this putative association to premature thelarche.<span id=\"992bf198-dd40-4496-925a-8462cbaeeefe\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"6fc1c879-ba25-4180-a029-dacb18c32d27\">2<\/sup><\/span>\u00a0Endocrine disrupting chemicals are natural or synthetic components that alter endocrine pathways by imitating, antagonizing or altering normal endocrine homeostasis.<span id=\"c2c5bf52-9c88-48bf-89fe-6bd12a094f9b\" class=\"jrnlBibRef\" data-citation-string=\" R3 \"><sup id=\"c8ad467b-c801-4a91-9a01-2a967dccb82c\">3<\/sup><\/span>\u00a0Gynaecomastia, which is usually caused by an imbalance between oestrogen-stimulating and androgen-inhibiting breast glandular tissue growth, is a common clinical condition associated with normal pubertal development, aging and various pathologies, including exposure to environmental endocrine disrupting agents.<span id=\"a47f3261-934f-4168-bc50-302ee9aeba6d\" class=\"jrnlBibRef\" data-citation-string=\" R4 \"><sup id=\"3f296705-4808-453c-95b4-6f5be92dd3af\">4<\/sup><\/span>\u00a0Prepubertal gynaecomastia is uncommon, usually idiopathic and in some instances has been linked to exogenous factors.<span id=\"33711594-3e16-454f-9952-cafb79c53498\" class=\"jrnlBibRef\" data-citation-string=\" R4 R5 \"><sup id=\"cc0fa6b3-1fae-46d0-8035-c2a298af0a1f\">4,5<\/sup><\/span>\u00a0Similarly, premature thelarche denotes early breast development in girls younger than 8 years, which also is idiopathic and transient in most instances.<span id=\"8e3a3d51-49a9-4982-95e7-7608956d16a6\" class=\"jrnlBibRef\" data-citation-string=\" R6 \"><sup id=\"afd57dff-985b-4292-ba1e-eec1d108ae89\">6<\/sup><\/span>\u00a0In this review, we will summarize the studies demonstrating the oestrogenic and antiandrogenic activities of LO and TTO, and critically analyze the reports of an association between use of these products and prepubertal gynecomastia and premature thelarche using Hill\u2019s criteria.<span id=\"4f2bbce0-02ad-4e78-b16f-194626ebfaa1\" class=\"jrnlBibRef\" data-citation-string=\" R7 \"><sup id=\"7aeb06fb-c1a8-4a87-a472-4c675054d379\">7<\/sup><\/span> We performed an Ovid literature search using search terms: \u201cgynaecomastia\u201d, \u201cprepubertal gynaecomastia\u201d, \u201cpremature thelarche\u201d, \u201cprecocious puberty\u201d, cross referenced with \u201clavender oil\u201d, \u201ctea tree oil\u201d, \u201cessential oils\u201d, \u201cendocrine disrupting agents\u201d, \u201cenvironmental estrogens\u201d and \u201cantiandrogens\u201d. Additional articles were identified through the reference sections of retrieved articles.<\/p>\n<h1 id=\"864a414f-3a3e-4991-9c62-531c3b0be15d\" class=\"jrnlHead1\">Lavender and\u00a0<span id=\"070c5e1c-b5c2-4455-b5cf-ea2caa1b2a46\" class=\"sty cts-2 changeCase\">tea\u00a0<\/span><span id=\"d1871d09-a986-4744-9745-e99e390d5c88\" class=\"sty cts-2 changeCase\">tree essential oils<\/span><\/h1>\n<p id=\"e313261c-ebf3-4a00-abaf-2a5214898181\" class=\"jrnlSecPara\">LO is derived by steam distillation from the flowers of the\u00a0<em id=\"9760aa54-783a-478a-bfbf-c3b149ca34df\">Lavandula<\/em>\u00a0genus of plants and has been used for centuries. Therapeutic benefits include antibacterial, antifungal, sedative and antidepressive properties, as well as smooth muscle-relaxing properties and healing effects for dermatitis, burns and insect bites.<span id=\"f680335c-8670-4d2a-b0dc-a41ebd6e250c\" class=\"jrnlBibRef\" data-citation-string=\" R8 \"><sup id=\"2df4b358-de17-456f-a401-e385e25a6a8c\">8<\/sup><\/span> It is used in skincare products and shampoos because of its fragrance and its possible antimicrobial effects.<span id=\"f5baa532-2176-4423-baef-279323512982\" class=\"jrnlBibRef\" data-citation-string=\" R8 \"><sup id=\"51f3b8d4-eb9c-4926-bf04-48a8b763da4c\">8<\/sup><\/span>\u00a0LO contains a multitude of compounds, the main ones being linalool (20\u201345%), linalyl acetate (25\u201347%), 1,8-cineole (eucalyptol; &lt;2.5%), \u03b2-ocimene, terpinen-4-ol (0.1\u20138%) and camphor (&lt;1.2%).<span id=\"2536ce78-a1b9-48d9-8b77-a78c31b060df\" class=\"jrnlBibRef\" data-citation-string=\" R7 \"><sup id=\"73740f91-8508-4d0d-a7ba-351364c149ab\">7<\/sup><\/span>\u00a0The two major components, linalool and linalyl acetate are absorbed through the skin, achieving peak plasma levels at 19<span id=\"a8200e90-bac9-41a6-8011-99808f4eaf75\" class=\"nonBreakingSpace\">\u00a0<\/span>min.<span id=\"060c0813-a508-43da-b9ab-7ca03ed5549c\" class=\"jrnlBibRef\" data-citation-string=\" R9 \"><sup id=\"a1c388be-97af-45fb-96eb-cb5ad736abe0\">9<\/sup><\/span><\/p>\n<p id=\"a2986848-0ff9-44d9-aaed-6c54bb99d9a8\" class=\"jrnlSecPara\">TTO is derived from steam distillation of the foliage and terminal branchlets of the <em id=\"acbbb469-3e51-407a-a6a3-841981cce48b\">Melaleuca <\/em>genus and has been used in a variety of cosmetic skin, hair and nail products in concentrations of<span id=\"1ec8cc41-283c-46a3-96ce-7b6d6f7a8233\" class=\"nonBreakingSpace\">\u00a0<\/span>\u22642%.<span id=\"f352c17b-187c-4b49-9755-9488b708b86a\" class=\"jrnlBibRef\" data-citation-string=\" R10 \"><sup id=\"5fad792e-ec6c-43cd-8665-612cef718e7b\">10<\/sup><\/span>\u00a0The main constituents are terpinen-4-ol (30\u201348%), \u03b1-terpinene (5\u201313%), \u03b3-terpinene (10\u201328%), 1,8-cineole (eucalyptol, trace-15%), \u03b1-terpineol (1.5\u20138%), limonene (0.5\u20131.5%), terpinolene (1.5\u20135%) and p-cymene (0.5\u20138%).<span id=\"8608940b-f27b-4eae-bea4-a2f16ad72cb0\" class=\"jrnlBibRef\" data-citation-string=\" R9 \"><sup id=\"3bb5ce6c-bc06-4fbe-9041-0da283b169d3\">9<\/sup><\/span>\u00a0Human skin penetration of each of the 15 tea tree oil components showed penetration of only terpinen-4-ol (3.7\u20138%) and \u03b1-terpineol (0.5\u20131.1%) during the 24<span id=\"d51ef926-a406-4301-ba25-ee99cf94fed5\" class=\"nonBreakingSpace\">\u00a0<\/span>h after application of a pure solution, and only 2.2\u20134% of terpinen-4-ol and no \u03b1-terpineol during the 24<span id=\"90f6d00a-15cb-46d3-ad77-6c7f83d9457c\" class=\"nonBreakingSpace\">\u00a0<\/span>h after application of a 20% TTO solution.<span id=\"504698a4-475e-4abf-bc0c-436723b9b677\" class=\"jrnlBibRef\" data-citation-string=\" R9 \"><sup id=\"b95db960-8046-4b96-89ef-5d28b9e821ba\">9<\/sup><\/span>\u00a0Another study of human skin penetration confirmed the passage of terpinen-4-ol and \u03b1-terpineol through the skin, but also found eucalyptol could penetrate.<span id=\"28cd53ad-0560-4004-8c1b-c715ed033dd9\" class=\"jrnlBibRef\" data-citation-string=\" R11 \"><sup id=\"3d30a43e-30a4-4a06-9d9e-426aad79df72\">11<\/sup><\/span><\/p>\n<p id=\"d8439f31-b6fa-4be7-8e68-ba0998b2cd08\" class=\"jrnlSecPara\">The chemical composition of any essential oil varies depending on factors including the species of the plant, the soil conditions, climate, type of fertilizer, parts of the plants that are used, age of leaves and method of distillation.<span id=\"71d6f8d7-9336-4af0-b65e-49ab6195e05e\" class=\"jrnlBibRef\" data-citation-string=\" R12 \"><sup id=\"8b72cf4b-4ba0-44ed-8eea-71021dfe3b0b\">12<\/sup><\/span><\/p>\n<h1 id=\"28026cee-45a6-4c42-ba34-e7a76f069b51\" class=\"jrnlHead1\"><em id=\"f2ce7304-4008-4c9c-a40e-0f7c97c5acd7\">In\u00a0<span id=\"a5189acc-599f-4bea-bc0d-6290e5565465\" class=\"sty cts-2 changeCase\">vitro<\/span><\/em><span id=\"3ffe9476-4e99-47e2-b959-9e5451c2f85e\" class=\"sty cts-2 changeCase\">\u00a0and non-human\u00a0<\/span><em id=\"b452e1b2-a5cc-46c4-94f1-c75829f91cf1\"><span id=\"46a6529b-e8b6-405a-ba54-e1245be9e48b\" class=\"sty cts-2 changeCase\">in vivo<\/span><\/em><span id=\"9db4d0da-76c8-4f09-ae31-e476dc4a3349\" class=\"sty cts-2 changeCase\">\u00a0studies of<\/span>\u00a0LO\u2019s and TTO\u2019s o<span id=\"60bbb779-14aa-4dd1-aa11-8b4080830cd7\" class=\"changeCase sty cts-2\">estrogenic and antiandrogenic activity<\/span><\/h1>\n<p id=\"37b7380f-d3ad-4154-a085-8ab6873931e8\" class=\"jrnlSecPara\">In their initial report, Henley et al. performed an\u00a0<em id=\"f609bc2f-4a8f-4d3e-a5fb-4bb3af04debb\">in vitro<\/em>\u00a0dose-response analysis of LO and TTO using the MCF-7 breast cancer cell line containing oestrogen receptors (ER\u03b1), to measure oestrogenic effects. The MCF-7 cells were transfected with an oestrogen-inducible luciferase reporter plasmid and three copies of an oestrogen receptor element (ERE), allowing the researchers to determine the response. Both LO and TTO stimulated an oestrogen-dependent response, with a maximum of 50% of the activity produced by 1 nM of 17\u00df-estradiol positive control. Tests with higher doses became cytotoxic to the cells. Additionally, LO and TTO increased the expression of the oestrogen-regulated genes, MYC, CTSD and IGFBP3. This response showed similar activity to the estradiol control (1 nM of 17\u00df-estradiol) and the response was reduced when treated with the ER\u03b1 antagonist, fulvestrant. They also evaluated the possibility that the two essential oils exhibited antiandrogenic properties, using an androgen receptor (AR) assay in MDA-kb2 breast cancer cell line transformed with an androgen-inducible mouse mammary tumour virus-luciferase reporter plasmid. Dihydrotestosterone (DHT) stimulates luciferase activity. When these cells were treated with the essential oils and DHT, suppression of luciferase activity occurred in a dose-dependent manner, like the effect of the antiandrogen flutamide, suggesting that components of the oils acted as an androgen-receptor blocker. They also showed that LO and TTO inhibited the expression of four genes stimulated by DHT: CYP4F8, Clorf116, UGT2B28 and SEC14L2. Henley and colleagues suggested that the oestrogenic and antiandrogenic effects of LO and TTO may be clinically important and \u201cthat susceptibility to gynaecomastia or other manifestations of endocrine disruption may require exposure to a threshold dose of these oils\u201d. They further indicated that the threshold might depend on factors such as concentration of the LO or TTO in the product, the duration, frequency and quantity of the product that is used, and the genetic characteristics of the person exposed to the essential oils.<span id=\"764a9da0-6ead-46a1-b4b4-6f0baed07390\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"7833d198-c777-4ae5-9395-7ff7c1c0286a\">1<\/sup><\/span><\/p>\n<p id=\"880e1669-3ff1-440c-999f-7e83ba07553d\" class=\"jrnlSecPara\">Further studies from this group were reported by Ramsey et al.<span id=\"d946f64e-8551-45c2-88ed-e1cfb2ce7d8c\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"aa71bb60-6b13-4508-8ae8-e488758413a0\">2<\/sup><\/span>\u00a0In addition to providing case reports on three girls with premature thelarche and one boy with prepubertal gynaecomastia \u2013 all of whom used LO, but not TTO \u2013 they provided extensive\u00a0<em id=\"1c43deac-2105-4e9c-afe5-e8fe21a50dd1\">in vitro<\/em>\u00a0data supporting oestrogenic and antiandrogenic activity of individual components of the essential oils. Ramsey and associates began by testing the ER\u03b1 ERE-mediated activity in cultured HepG2 cells transfected with human ER\u03b1 and ERE and tested an estradiol control (E<sub id=\"2a798d1d-dd15-4586-ad17-1eaf3bd9ce4c\">2<\/sub>), both LO and TTO, and several constituents of the products. E<sub id=\"470d3686-48d2-4e87-a656-572cbc345d5e\">2<\/sub>\u00a0resulted in an almost 50-fold increase in the ERE-mediated promotor activity, while both essential oils showed an approximately 20-fold increase in activity. For the common constituents, \u03b1-terpineol showed the highest response (&gt;8 fold increase), followed by terpinen-4-ol (&lt;8 fold increase). Eucalyptol, dipentene\/limonene and \u03b1-terpinene showed little to no activity response, while \u03b3-terpinene showed a threefold increase at the highest dose. In the LO specific constituents, linalool showed a higher activity response (&lt;8 fold increase) than linalyl acetate (fourfold increase). Using the same procedure with HepG2 cells cotransfected with SRC-2, a coactivator specific to humans, and ER\u03b1, E<sub id=\"0b4b16e4-1770-4421-b625-6fb977c80262\">2<\/sub>, TTO, and LO showed significant increases in activity when SRC-2 was also present, while the essential oil components were more selective. Only terpinen-4-ol, \u03b1-terpineol, \u03b3-terpinenel and linalyl acetate showed ER\u03b1 activity in the SRC-2 cultured cells. A further examination, using HepG2 cells transfected with pG5 luciferase and pM-SRC-2-NR, showed that \u03b1-terpineol, linayl acetate and linalool can bind to the ligand-binding domain of ER\u03b1, and thus are able to activate SRC-2. To ensure the binding to the ER\u03b1 led to a functional outcome, the gene expression of three ER\u03b1-regulated genes (GREB1, PGR, CTSD) was examined after treatment of the MCF-7 breast cancer cells with the essential oils and their constituents. Except for PGR expression in the presence of LO, all genes were expressed to a greater or lesser degree by the individual components, and the gene expression was inhibited by an ER\u03b1 antagonist.<\/p>\n<p id=\"7ce3f102-ed82-4b47-bb4b-b9b1693e1e52\" class=\"jrnlSecPara\">To evaluate the antiandrogenic properties that Henley et al. observed, Ramsey et al. used the promoter activity of the androgen receptor (AR) mouse mammary tumour virus (MMTV) in MDA-kb2 cells.<span id=\"d42420c1-5d5c-45b1-bfbf-afcdddb26e74\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"7a70d8c8-3fd6-4127-a06a-72341ceb4633\">2<\/sup><\/span>\u00a0If stimulated with androgens, the activity of MMTV will increase. When added along with testosterone, both LO and TTO significantly inhibited MMTV activity at all concentrations. Tetpinen-4-ol, \u03b1-terpineol, \u03b3-terpinene, linalyl acetate and linalool reduced MMTV activity and no response or change in activity occurred when eucalyptol was present. The study also included an investigation of the essential oils\u2019 effect on AR-regulated gene expression. Three AR target genes (SEC14L2, CYP4F8 and UGT2B28) were cultured with MDA-kb2 cells, and gene expression was evaluated with each oil and constituent. With all tested materials, SEC14L2 showed no gene expression. All constituents, except for eucalyptol and \u03b1-terpineol, blocked CYP4F8 activity. Only terpinen-4-ol, \u03b1-terpineol, linalyl acetate and linalool halted gene expression for UGT2B28.<span id=\"0cd29531-60d9-483d-b11e-bc1edffbfdcc\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"fa5a74fc-a147-4b45-8090-fd8131653f31\">2<\/sup><\/span>\u00a0It should be noted that, while these results show oestrogenic and antiandrogenic properties for TTO, LO and their major constituents, the tests were done\u00a0<em id=\"2988153f-0a0b-48ad-a515-f3e5d4baae52\">in vitro<\/em>\u00a0and cannot be assumed to verify an\u00a0<em id=\"0e1b94f3-f726-41e3-8a9e-1a6309a8b2f6\">in vivo<\/em>\u00a0hypothesis.<\/p>\n<p id=\"51e11584-2e26-4f82-a522-a8e36a2b52d5\" class=\"jrnlSecPara\">Several groups affiliated with the essential oil industry have criticized the\u00a0<em id=\"e9400831-7fe5-48de-b660-26ed7c316d8e\">in vitro<\/em>\u00a0studies of Henley, et al. and Ramsey and co-workers on methodological grounds.<span id=\"54054eeb-c3ed-4948-9865-c01eb27a8d85\" class=\"jrnlBibRef\" data-citation-string=\" R13 R14 R15 \"><sup id=\"da56c25d-49ef-4594-af0f-ec0109b3055f\">13\u201315<\/sup><\/span>\u00a0They point to early studies demonstrating that polystyrene present in tissue culture dishes like those used by Henley and Ramsey contain oestrogenic substances such as alkylphenols, phthalates and bisphenol A, which can be released in the presence of essential oils and stimulate the MCF-7 cells. In contrast, vegetable oils like the ones used by Ramsey as a control to examine the possibility of such leaching does not do this to any appreciable effect.<span id=\"c8ec7fcd-63d0-440e-96fc-5bfdc477b6ff\" class=\"jrnlBibRef\" data-citation-string=\" R16 R17 R18 \"><sup id=\"348e18a8-7a1a-42d1-8daa-d628ee786fea\">16\u201318<\/sup><\/span>\u00a0Additionally, the Henley group used Dulbecco\u2019s Modified Eagle Medium, which according to Larkman, enhances the leaching effect.<span id=\"a6151e7b-99ae-4499-80bd-93c8217c11d1\" class=\"jrnlBibRef\" data-citation-string=\" R14 \"><sup id=\"f90af6d2-c6cf-4151-b42b-77b3d25c886a\">14<\/sup><\/span>\u00a0However, Ramsey and colleagues did note that their experiments with essential oils showed varying activity and that some showed no activity. If the essential oils leached substantial amounts of oestrogenic substances out of the plastic, one would expect to see a positive oestrogenic effect in all the studies, which was not the case.<span id=\"e7ce31b7-3ed6-46d8-b9c9-0ed18935f8a6\" class=\"jrnlBibRef\" data-citation-string=\" R19 \"><sup id=\"860d5eb7-892f-4504-be89-42448b417dbd\">19<\/sup><\/span><\/p>\n<p id=\"827d8929-dec9-4efc-ab0b-1f62189ee940\" class=\"jrnlSecPara\">Prior to the studies of Henley and Ramsey, Perry and colleagues examined the\u00a0<em id=\"7c01900a-7651-4082-b8b1-8f4ba3647fb4\">in vitro<\/em>\u00a0oestrogenic activity of the essential oil from a member of the lavender family,\u00a0<em id=\"f562b2e1-2385-4863-96e4-46125c98f92d\">Salvia lavandulaefolia<\/em>\u00a0Vahl. (Spanish sage). Using the induction of \u03b2-galactosidase activity in a recombinant oestrogen-inducible yeast assay, they found the essential oil demonstrated weak oestrogenic activity, although it was not significantly different from the control because of high variability. However, geraniol, which comprised &lt;1% of the essential oil, did show significant oestrogenic activity, while \u03b1-pinene, \u03b2-pinene, 1,8-cineole and thujone did not.<span id=\"b0105fcb-581d-4f7b-9da4-8d048bb36514\" class=\"jrnlBibRef\" data-citation-string=\" R20 \"><sup id=\"a47202e7-a070-48a8-bcbb-686ce63bd627\">20<\/sup><\/span><\/p>\n<p id=\"b3f1ac70-490b-43a7-bf3e-4e2602748f7f\" class=\"jrnlSecPara\">Using a sensitive bioassay with recombinant yeast cells expressing the human ER, Howes and co-workers confirmed that geraniol had estrogenic activity, while eugenol, which is present in both LO and TTO, had anti-oestrogen effects.<span id=\"3e547df6-8ec6-47b1-a984-e27002aadc1d\" class=\"jrnlBibRef\" data-citation-string=\" R21 \"><sup id=\"5fb706e2-01e5-4cc9-9f36-7198a93db3e1\">21<\/sup><\/span>\u00a0Both compounds were capable of displacing E<sub id=\"34a74ac9-4ec3-470b-8391-b1ae220bdc25\">2<\/sub>\u00a0from isolated ERs, but neither showed oestrogenic or anti-oestrogenic activity in an oestrogen-responsive human cell line (Ishikawa-Var I). In an androgen-inducible yeast screen, neither geraniol nor eugenol had androgenic or antiandrogenic activity.<span id=\"0b8af376-04ae-4579-9062-36a9375a06dc\" class=\"jrnlBibRef\" data-citation-string=\" R21 \"><sup id=\"b0d24b1d-70d5-4ac5-a69a-0f5e725f704b\">21<\/sup><\/span><\/p>\n<p id=\"d4d56320-941b-47c7-9c85-d0d9d53a07c8\" class=\"jrnlSecPara\">Nielsen used the MCF-7 BUS cell subline cell proliferation assay to compare the response of TTO and its constituents to the effect of graded doses of E<sub id=\"83cd32d8-d9f1-4004-aa49-b9880e5e1d43\">2<\/sub>. TTO showed a weak, but dose-dependent oestrogenic response, with the maximum response being 34% of the peak E<sub id=\"167adb98-6511-4f0e-9039-1f0a533e888c\">2<\/sub>\u00a0response. Neither terpinen-4-ol nor \u03b1-terpineol or eucalyptol induced cell growth above 10% of the maximum E<sub id=\"dbd982ee-ad61-4269-8099-766fb6927be7\">2<\/sub>\u00a0response. Terpinen-4-ol slightly reduced the E<sub id=\"de14e428-2c4f-421f-b6a7-3ba99ba365d1\">2<\/sub>\u00a0stimulation in this assay, while \u03b1-terpineol caused a significant inhibition indicating an anti-oestrogenic activity. Of importance, none of the TTO constituents which have been shown to be absorbed through the skin alone or in combination showed oestrogenic activity. Based on these findings, the author concluded that\u00a0<em id=\"7c5f4d05-a3ba-4a80-85c0-a37c36a2e560\">in vivo<\/em>\u00a0results cannot be extrapolated from the\u00a0<em id=\"cab57853-cfc3-42f9-a420-f27dddb229b8\">in vitro<\/em>\u00a0responses and, if there is a connection between the application of TTO and endocrine disrupting activities, there must be another causation factor. That factor could be another constituent that penetrated the skin unnoticed, however, this is highly unlikely.<span id=\"0e9a6b35-8c7e-4821-b269-1bb610928370\" class=\"jrnlBibRef\" data-citation-string=\" R22 \"><sup id=\"ae7c3a62-3dc3-43c5-b9c2-93f2fbe16f69\">22<\/sup><\/span><\/p>\n<p id=\"6ead4fb2-daf6-482b-b061-d7857675d1f7\" class=\"jrnlSecPara\">Simoes and associates utilized an oestrogen response element-luciferase reporter assay with MCF-7 cells to examine the oestrogenic and anti-oestrogenic activities of essential oils. In contrast to the studies by Henley and Ramsey, LO demonstrated non-significant minimal stimulation of the ERE-luciferase activity and little or no stimulation of MCF-7 cell growth.<span id=\"e4f5e780-989c-4f1e-a5bf-e2794b0b7838\" class=\"jrnlBibRef\" data-citation-string=\" R23 \"><sup id=\"8b22652f-c9a7-4e44-be8e-f1c7257815d4\">23<\/sup><\/span><\/p>\n<p id=\"4dd23cb0-b079-47c3-bcdf-5ad202519f26\" class=\"jrnlSecPara\">An analysis of the oestrogenic and anti-oestrogenic activity of ethanol extracts of hair and skincare products utilizing a cell proliferation assay with the oestrogen sensitive MCF-7:WS8 cell line showed that the product containing TTO had no oestrogenic activity, but did exhibit anti-oestrogenic activity, while the product with geraniol showed neither oestrogenic nor anti-oestrogenic activity.<span id=\"860dfec7-eeef-4bbf-a690-cdc16010663f\" class=\"jrnlBibRef\" data-citation-string=\" R24 \"><sup id=\"e70f1874-9063-40b9-9749-6a47261e07e5\">24<\/sup><\/span><\/p>\n<p id=\"94489766-49e0-4452-b00d-18be895d4ce9\" class=\"jrnlSecPara\">A recent study, reported only in abstract form, indicated that some essential oil metabolites, including eucalyptol, inhibited CYP17A1 (17\u03b1-hydroxylase and 17,20-lyase) activity in an adrenal cell line.<span id=\"ecc7a01e-ffde-49c9-a9c8-154aaf2930fb\" class=\"jrnlBibRef\" data-citation-string=\" R25 \"><sup id=\"554a1c5f-9843-491d-8f6c-ac599f71755c\">25<\/sup><\/span>\u00a0This could potentially decrease androgen production if the metabolites had sufficient skin penetration. The authors also indicated that some constituents inhibited CYP19A1 (aromatase) activity, which would potentially reduce oestrogen production.<span id=\"d4b2bac2-a248-41d8-b2eb-9f91c69aebf2\" class=\"jrnlBibRef\" data-citation-string=\" R25 \"><sup id=\"d14858c0-499f-40ae-8562-4aabe7b6acf2\">25<\/sup><\/span>\u00a0Indeed, in an\u00a0<em id=\"3fa6596c-5889-410a-b226-cf19e3ef8659\" class=\"sty cts-5\">in vitro<\/em>\u00a0<em id=\"38f46047-5cc9-4792-880a-614a36cc4784\" class=\"sty cts-5\"><\/em>assay using placental cells, eucalyptol and limonene decreased E<sub id=\"1ed1ca70-f99c-49e3-8922-824a6933beb9\">2<\/sub>\u00a0production, while 4-terpineol increased progesterone and E<sub id=\"4f162265-3fb0-48b0-89be-4e3186d3a8f6\">2<\/sub>\u00a0secretion in a dose-independent manner.<span id=\"c5ed09bf-152d-4105-b951-1d7b96e93034\" class=\"jrnlBibRef\" data-citation-string=\" R26 \"><sup id=\"7f8a7538-362d-4398-a80f-001a6febe25d\">26<\/sup><\/span>\u00a0Again, as with the other studies summarized above, it is not possible to extrapolate the\u00a0<em id=\"0c86ce38-31f0-4afa-82f2-46af810a7ea4\">in vitro<\/em>\u00a0findings to the\u00a0<em id=\"0d804a66-effe-4e33-9b0b-8b3e2fc053de\">in vivo<\/em>\u00a0situation where absorption, distribution, metabolism and excretion exert dominant roles on tissue exposure and response.<\/p>\n<p id=\"280a534f-07b4-40ff-8b4c-e3b0dd68880e\" class=\"jrnlSecPara\">The disparate results from the different\u00a0<em id=\"aa09a313-7b1b-4030-9e33-4dfbea7b9737\">in vitro<\/em>\u00a0studies likely relate to differences in the assay methodology, as well as the source, potential contaminants in the preparations, and concentrations of the multiple constituents in the essential oils.<\/p>\n<p id=\"b7594dc7-8902-4a60-9984-c884ca2798d8\" class=\"jrnlSecPara\">In addition to the\u00a0<em id=\"7dc6354f-1b1b-40e7-9c66-23685580adc4\">in vitro<\/em>\u00a0studies, there exist a small amount of animal data, which also have conflicting results. When tested\u00a0<em id=\"e9db21e7-8ae4-4a5d-9e8b-b6680470691e\">in vivo<\/em>\u00a0using a uterotrophic assay in immature female rats exposed to LO through the dermal route in doses that were equivalent to 6,000\u201330,000 times the maximum daily human exposure, and greater than 5,000\u20131,000,000 times the estimated exposure from hair and skincare products that may be used by prepubertal boys, Politano and co-workers concluded that, at the dosages tested, LO is not an oestrogenic agent.<span id=\"a8ae6279-796c-4ed9-9970-4aa6275ea792\" class=\"jrnlBibRef\" data-citation-string=\" R27 \"><sup id=\"d02d41b2-2e08-463e-b380-01fae679d105\">27<\/sup><\/span>\u00a0Howes et al. examined the effect of geraniol in ovariectomized mice and did not find the usual oestrogen-induced uterine hypertrophy or acute increase in uterine vascular permeability.<span id=\"7de21943-7aed-4e98-8ae3-a70e87c8cb83\" class=\"jrnlBibRef\" data-citation-string=\" R21 \"><sup id=\"2d000ea2-8f23-4933-a5f9-398336b30fee\">21<\/sup><\/span>\u00a0Exposure of prepubertal female rats to LO via nasal spray or indoor exposure via a LO diffuser triggered early puberty with earlier vaginal opening, significantly higher follicle-stimulating hormone (FSH), luteinizing hormone (LH) and non-significantly higher E<sub id=\"a0878e43-662b-4abe-848b-7a8e4fc1f54d\">2<\/sub>\u00a0levels than in control rats. This is not what would have been expected with LO having\u00a0<em id=\"b71c8c24-05e5-4e3b-824a-6763ab84743b\">in vivo<\/em>\u00a0oestrogenic activity, which would have suppressed gonadotropins and E<sub id=\"0231b8fa-a4f7-4407-9cf1-04d5cd81e38b\">2<\/sub>. Indeed, the authors thought that the mechanism of action was probably through olfactory stimulation of the hypothalamus, rather than a hormonal effect.<span id=\"db296f7c-27d9-4c92-8814-e1b5cda1c0d1\" class=\"jrnlBibRef\" data-citation-string=\" R28 \"><sup id=\"3dc3b046-17da-4e0b-b3cb-36269d2e796b\">28<\/sup><\/span>\u00a0In contrast to the above studies showing no\u00a0<em id=\"12ec9141-154c-4e11-9942-e20683e8b72f\">in vivo<\/em>\u00a0oestrogenic effect of LO, Slighoua and co-workers reported an increase in uterine weights and serum E<sub id=\"ec97c32e-a3bc-4250-a4ef-cb98d032576c\">2<\/sub>\u00a0levels of female rats treated with hydro-ethanolic extracts of\u00a0<em id=\"f9634e8c-c717-4bf2-8b03-f0189e32f728\">Lavandula officinalis<\/em>\u00a0Chaix.<span id=\"6fe8dfc4-c8b2-42de-85df-5162d37d40f9\" class=\"jrnlBibRef\" data-citation-string=\" R29 \"><sup id=\"aa55b594-86fe-4155-a611-3dd03e7cb0d3\">29<\/sup><\/span>\u00a0These extracts contained phenolic compounds, but it is unknown whether they also contained linalool or linalyl acetate, as found in LO. The results of the\u00a0<em id=\"4643b1d5-c30b-4abc-a21e-3e729007a8b7\" class=\"sty cts-9\">in vitro<\/em>\u00a0and\u00a0<em id=\"47c40467-b060-49e3-8b03-ec35c6b48fae\" class=\"sty cts-9\">in vivo<\/em>\u00a0studies are summarized in\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T1 \">Table 1.<\/span><\/em><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-67507\" src=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-1.png\" alt=\"\" width=\"516\" height=\"671\" srcset=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-1.png 516w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-1-231x300.png 231w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-1-461x600.png 461w\" sizes=\"auto, (max-width: 516px) 100vw, 516px\" \/><\/p>\n<p id=\"d4834659-a662-4c4a-977b-efa0ce2fd13f\" class=\"jrnlSecPara\">There have been a few human studies using essential oils that have examined the effects on reproductive hormones. Cohn and associates studied topical application of LO and TTO in postmenopausal women with hot flashes. There were no significant differences between on treatment and baseline FSH levels and hot flash frequency or severity, and the investigators concluded that LO and TTO did not have oestrogenic effects.<span id=\"9dffd121-5ba0-4dc0-a785-cf16b3fb0820\" class=\"jrnlBibRef\" data-citation-string=\" R30 \"><sup id=\"aa4341ee-4fb4-434a-a806-a5d2b5bbd50a\">30<\/sup><\/span> Heger-Mahn et al. performed a double-blind, randomized, placebo-controlled trial examining the effects of an oral LO preparation on the pharmacokinetics and pharmacodynamics of an ethinyl estradiol\/levonorgestrel oral contraceptive in adult women, and did not demonstrate any relevant changes in the parameters or in the levels of progesterone, E<sub id=\"e52cf854-02cd-402d-b07c-1b5b484893fc\">2<\/sub>\u00a0or sex-hormone-binding globulin. There were no effects on mean endometrial thickness or ovarian follicle size.<span id=\"34ac13fe-b774-41b9-b72f-b13012e6ba00\" class=\"jrnlBibRef\" data-citation-string=\" R31 \"><sup id=\"26c786d3-802b-4c9b-85bf-83db1a2b1f99\">31<\/sup><\/span>\u00a0In a study of peri- and postmenopausal women exposed to aromatherapy with different essential oils, there was no effect of LO on salivary oestrogen concentrations.<span id=\"dc0f66bf-8826-422b-85ec-c78a1bef5685\" class=\"jrnlBibRef\" data-citation-string=\" R32 \"><sup id=\"ce4c29a6-d3f2-459e-8c03-0ca9e49879ec\">32<\/sup><\/span> Thus, the human studies that have examined possible clinical oestrogenic activity of LO or TTO have not shown it to be present.<\/p>\n<p id=\"b3cc4db6-af64-4158-ab76-be4104131526\" class=\"jrnlSecPara\">Investigating whether LO and TTO may have clinical antiandrogenic effects, Tirabassi et al. examined the effect of a LO and TTO spray on women with idiopathic hirsutism. This randomized, open-label, placebo-controlled study involved treating the hirsute areas twice daily for three months. There were no significant differences between groups or between baseline and three months in the levels of FSH, LH, E<sub id=\"d0908be1-74b9-4130-af94-22bb1d832402\">2<\/sub>, total or free testosterone, progesterone, 17-hydroxyprogesterone, sex-hormone-binding globulin, dehydroepiandrosterone sulfate, or \u0394<sup id=\"c1a76393-5ed7-4ecd-b9cd-4b0fdabec230\">4<\/sup>-androstenedione.<span id=\"d62a2b84-1c89-45a1-b31d-9f55a6f8a57b\" class=\"jrnlBibRef\" data-citation-string=\" R33 \"><sup id=\"64ee197d-a2bb-4e07-926d-dd9ac78b66b1\">33<\/sup><\/span> Nevertheless, there was a statistically significant decrease in the Ferriman-Gallway hirsutism score and hair diameter, suggesting a topical effect on hair growth rather than a systemic effect.<span id=\"3f5e61ec-146f-40b7-a7c7-51664a90e4ef\" class=\"jrnlBibRef\" data-citation-string=\" R33 \"><sup id=\"7cec94ec-9395-419b-9562-beb45a153f66\">33<\/sup><\/span><\/p>\n<h1 id=\"276bd180-336c-4ffd-84e4-79ea3831003d\" class=\"jrnlHead1\">Reports of\u00a0<span id=\"4c5bef14-eba1-4a9e-97f4-38ed840ddc08\" class=\"changeCase sty cts-2\">prepubertal gynaecomastia and premature thelarche in children exposed to<\/span>\u00a0LO and\/or TTO<\/h1>\n<p id=\"00fb8a40-032a-4614-b9c9-fdcec6d72a01\" class=\"jrnlSecPara\">As noted above, the putative association arose from the study of Henley et al., who described three prepubertal males diagnosed with gynaecomastia, each of whom used regular topical applications of lavender and tea tree products.<span id=\"cd5d0479-d451-43c2-a8f2-d7a2e0fb494c\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"65384d15-7f19-41b0-b74b-063d407f67b1\">1<\/sup><\/span>\u00a0However, the product names or ingredients were not identified in the report. Each otherwise healthy boy had spontaneous breast development. Patient 1, aged 4 years and 5 months, had been exposed to a LO-infused \u201chealing balm\u201d before the initial diagnosis. After ceasing application of the balm for 4 months, his breast size decreased from 2.5 cm by 2.5 cm to 1.5 cm by 1.5 cm.<span id=\"fa7dcd9f-58e7-4c02-8b06-8a8b6c84975d\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"4253832f-9408-4719-88c3-70cb129fba50\">1<\/sup><\/span>\u00a0A second patient (patient 2), aged 10 years and 1 month, used a hair gel and shampoo containing both LO and TTO every morning. Both he and his mother noticed that the condition was more pronounced in the evening than the morning. Within 9 months of ceasing to use the hair products, the patient\u2019s gynaecomastia had resolved. Patient 3, aged 7 years and 10 months, regularly used a lavender-scented soap and occasionally applied lavender-scented skin lotion. After he ceased using the products, his gynaecomastia resolved. His fraternal twin used the same lavender-scented lotion but did not exhibit gynecomastia.<span id=\"896e978a-1ad2-4bd4-963f-fc06e0f0220c\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"9095b4b1-adcd-434d-8a9b-22c836081ebc\">1<\/sup><\/span>\u00a0After showing\u00a0<em id=\"c96807c1-25a0-4cbc-9adb-c9bec98021d7\">in vitro<\/em>\u00a0oestrogenic and antiandrogenic activity of LO and TTO, the authors proposed that these essential oils were the cause of the prepubertal gynaecomastia.<span id=\"28b6d51b-54f1-4dee-9397-4f922595ec98\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"82f81a1d-4234-4fc0-9fc1-2e9687b39209\">1<\/sup><\/span><\/p>\n<p id=\"0a5c1d11-49f5-4d06-a1f2-673cb33ed7a8\" class=\"jrnlSecPara\">Along with the three initial patients described by Henley et al., an additional nine patients who were reported to use a product containing LO or TTO were subsequently diagnosed with either prepubertal gynaecomastia (total n=8) or premature thelarche (n=4) (<em><span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>).<span id=\"c4b5b5dc-11b7-49ad-a700-e5f97a07dd94\" class=\"jrnlBibRef\" data-citation-string=\" R1 R2 R27 R28 R29 \"><sup id=\"9ea876d2-08ad-47c2-abdf-f561b310bcf3\">1,2,27\u201329<\/sup><\/span>\u00a0Three of the eight boys had Tanner genitalia staging, and all were stage 1. Eight of the twelve children also had Tanner pubic hair staging. Seven of the eight were also Tanner stage 1, while one was Tanner stage 2.1,2,34,35 The latter (patient 2 in\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>) had an increase in free testosterone and DHEA-S, suggesting that he had transitioned to early puberty. Only two of the twelve patients used a product containing TTO. One (patient 2 in Henley et al.) used a styling gel and shampoo with both LO and TTO. The other patient, described by Lopez-Rodriguez and Marcos, used a shampoo, to which four drops of TTO was added to prevent head lice.<span id=\"3a484b7f-3caf-4038-9dd6-01be1b8c982d\" class=\"jrnlBibRef\" data-citation-string=\" R34 \"><sup id=\"0fe29b57-785b-4e59-b2f4-092eb9a9940c\">34<\/sup><\/span>\u00a0This was the only patient described who used TTO exclusively. Diaz et al. reviewed three patients who presented with prepubertal gynaecomastia.<span id=\"6cafe9f7-7d8b-4844-ad02-5436022a249e\" class=\"jrnlBibRef\" data-citation-string=\" R35 \"><sup id=\"6c8f3b85-1247-43d7-adc1-5dae04ac3461\">35<\/sup><\/span>\u00a0Of the three, two used the product \u201cAguas de Violetas\u201d, a lavender-based cologne. The other patient used an unidentified shampoo for a year. When each patient ceased application of the products, the gynaecomastia resolved within months (see\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>). In the publication by Ramsey et al., four more patients were recorded with prepubertal breast development.<span id=\"a51e9a35-e632-4c49-8fe5-d785f6d89a78\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"43ade021-6017-4c57-a477-cd4e3b502ca5\">2<\/sup><\/span> One boy (patient 8), aged 7 years and 11 months, used \u201cCrusellas Violet Water\u201d, and was reported to have gynaecomastia for 4 years, before he discontinued his use of the lavender-infused product and it was resolved. One girl (patient 10), aged 7 years and 6 months, used \u201cMi tesoro Agua de Violetas\u201d continuously until advised to stop, and her thelarche resolved 6 months later.<span id=\"ac419f4e-0dfa-4114-a84d-5a0216f76a8f\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"27fa27ef-f8bd-49d1-8ede-faad15496db5\">2 <\/sup><\/span>\u00a0Another patient (patient 11), reported to have premature thelarche for almost 3 years, had used \u201cBaby Magic Calming Baby Bath Lavender and Chamomile\u201d since infancy but, on stopping, her breast development resolved.<span id=\"f30756f6-2911-4850-b326-5b08d7884cf0\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"0e245351-2587-4e96-97e6-03de61b28926\">2<\/sup><\/span>\u00a0The last patient (patient 12) recorded by Ramsey et al. sat next to her teacher\u2019s LO diffuser for 1 year at school. During that year, she was recorded to have premature thelarche, and upon switching seats, it resolved.<span id=\"7cb9249d-ff67-4972-aea5-d9e60e8f4454\" class=\"jrnlBibRef\" data-citation-string=\" R2 \"><sup id=\"99cc6816-656a-4bfb-b6e8-0eeef8f29c40\">2<\/sup><\/span>\u00a0One other patient (patient 9) reported to have premature thelarche used wipes, shampoo, body wash, moisturizing cream and skin-smoothing lotion containing LO. Her thelarche resolved after ceasing use of LO infused products.<span id=\"ca01b870-3c54-4ee2-b884-dab0b8ccdffe\" class=\"jrnlBibRef\" data-citation-string=\" R36 \"><sup id=\"a7434455-8a64-4583-94f0-7703450bd6ef\">36<\/sup><\/span>\u00a0In each of the patients noted above, there was a clear temporal relationship between the use of LO and\/or TTO and the appearance of premature breast development. Additionally, the breast tissue regressed or disappeared after discontinuation of the LO or TTO. None reported a rechallenge test with the product thought to cause the breast enlargement. This is especially important, since both prepubertal gynaecomastia and premature thelarche often regress spontaneously.<span id=\"5cceb3d1-f8fd-4178-a5dc-fdde90ee931f\" class=\"jrnlBibRef\" data-citation-string=\" R5 R6 \"><sup id=\"930b477e-3232-4e60-b1fa-24354369dade\">5,6<\/sup><\/span><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-67512 size-full\" src=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302.png\" alt=\"\" width=\"1142\" height=\"744\" srcset=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302.png 1142w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302-300x195.png 300w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302-1024x667.png 1024w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302-800x521.png 800w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-e1700494989302-768x500.png 768w\" sizes=\"auto, (max-width: 1142px) 100vw, 1142px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-67517 size-full\" src=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421.png\" alt=\"\" width=\"1131\" height=\"322\" srcset=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421.png 1131w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421-300x85.png 300w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421-1024x292.png 1024w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421-800x228.png 800w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-2-cont-e1700495002421-768x219.png 768w\" sizes=\"auto, (max-width: 1131px) 100vw, 1131px\" \/><\/p>\n<div id=\"f03e7674-ab9e-4d43-a995-99a2f1ffe4f9\" class=\"jrnlTblBlock\">\n<div id=\"c16dc26f-beb5-4300-8696-37b8fe0a58fa\" class=\"jrnlTblFootGroup\">\n<div id=\"4a685a6b-bd85-4154-bc0c-19a15c0ae4ae\" class=\"jrnlTblFoot\">\n<p class=\"jrnlTblFootText\">Unlike the above reports with patient-specific details, Block reviewed the charts of about 1,100 children under six years in his practice and noted that 33 under the age of 5 had prepubertal gynaecomastia (n=5) or premature thelarche (n=28). Twelve of these 33 patients had a history of LO or TTO use. However, the relationship of this to the onset of the breast development, the name of the product, duration of use, and whether the breast enlargement resolved while they were using the LO- or TTO-containing skin or scalp creams or lotions, or whether the breast enlargement disappeared after cessation of the use of the skin lotions, was not described.<span id=\"0563346c-9960-4eda-9e2b-990ea5e39e54\" class=\"jrnlBibRef\" data-citation-string=\" R37 \"><sup id=\"5f7de2bb-f9e8-48ad-9231-5717e3d6e72f\">37<\/sup><\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n<p id=\"0a0c079a-1012-409b-ab26-b544ced0551d\" class=\"jrnlSecPara\">These reports have been heavily criticized on several grounds, with most of the criticism emanating from scientists associated with the essential oil industry raising the possibility of commercial bias.<span id=\"65350ddf-2442-4c4c-8121-68a5020d6912\" class=\"jrnlBibRef\" data-citation-string=\" R13 R14 R15 R38 R39 R40 R41 R42 R43 \"><sup id=\"2a20ae95-50a4-4d79-a196-74deeb0388a3\">13\u201315,38\u201343<\/sup><\/span>\u00a0First, there has been considerable controversy as to whether the products used by some of these children actually contained LO or TTO. As noted, the skincare products and shampoos used by the children in the Henley et al. study were not named, but the authors indicated that they had found the ingredients listed on the manufacturers\u2019 websites.<span id=\"30a31014-4594-435b-b076-7c858dde088a\" class=\"jrnlBibRef\" data-citation-string=\" R44 \"><sup id=\"509ba907-e79c-4497-8750-faf244579c8a\">44<\/sup><\/span>\u00a0A concern was raised that three of the products used by patients in the Ramsey et al. study may have been mislabelled as containing LO. Assays of the products \u201cCrusellas Violet Water\u201d cologne and \u201cBaby Magic Calming Baby Bath Lavender and Chamomile\u201d soap were done by gas chromatography-mass spectrometry and liquid chromatography with tandem mass spectrometry.<span id=\"f222c58b-2849-42d5-8274-6ca4398aafed\" class=\"jrnlBibRef\" data-citation-string=\" R13 \"><sup id=\"ebe8c272-dccd-4bf7-840e-62298ee7cf7e\">13<\/sup><\/span>\u00a0LO was not found to be a component of the Crusellas Violet Water cologne, however, another potential endocrine disruptor, diethyl phthalate, was. The Baby Magic Calming Baby Bath soap had a composition containing a \u201cvery low\u201d amount of LO.<span id=\"0906f065-a6fb-4b25-b2e6-010603f0a9ea\" class=\"jrnlBibRef\" data-citation-string=\" R13 \"><sup id=\"ca367b7d-fb4b-48ae-977f-64719a4cade7\">13<\/sup><\/span>\u00a0A further study was done on the products \u201cCrusellas Violet Water\u201d cologne and \u201cMi Tesoro Agua de Violetas\u201d cologne, along with several other known products labeled \u201caguas\u201d (Augustin Reyes, PMB Agua de Violetas, AFFA Violetas Francescas). The assay showed that the composition of all products did not contain linalyl acetate. Except for the Augustin Reyes product, which had a 2.28% composition of linalool, the products also did not contain linalool.<span id=\"bcfcff22-86f5-4847-91d7-0b5514a8b8bc\" class=\"jrnlBibRef\" data-citation-string=\" R14 \"><sup id=\"75f56c85-80a7-4b11-b42c-8d0355a46228\">14<\/sup><\/span>\u00a0The 2.28% composition of linalool in the Augustin Reyes product falls well below the ISO Standard of 25\u201338%.<span id=\"9ce27a02-530c-4b93-b907-8bea8a74f884\" class=\"jrnlBibRef\" data-citation-string=\" R39 \"><sup id=\"ca12c4ae-415a-44b2-a013-5c79dea9e537\">39<\/sup><\/span>\u00a0Conversely, Diaz et al. used high performance liquid chromatography and mass spectroscopy to analyze the \u201cagua de violetas\u201d cologne used by one of his patients (Patient 6 in\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>) and identified both linalool and linalyl acetate confirming the presence of LO in the product.<span id=\"91c4313d-340b-4702-b4c5-7e77991be387\" class=\"jrnlBibRef\" data-citation-string=\" R35 \"><sup id=\"3f4fcf4a-bb60-496b-b11f-33e241efd6b8\">35<\/sup><\/span><\/p>\n<p id=\"140557c1-73f8-4803-a1f9-b04c1e691c00\" class=\"jrnlSecPara\">There are several lines of evidence against TTO having any potential clinical effect regarding estrogen or antiandrogen activities. The second patient listed by Henley et al. was the only initial case reported using TTO, as well as LO.<span id=\"af783520-cfce-4724-a575-88fac20c6e75\" class=\"jrnlBibRef\" data-citation-string=\" R1 \"><sup id=\"3859e0f3-e7e3-4226-ae83-28b6788ac728\">1<\/sup><\/span>\u00a0It has been reported that a further investigation into the products used by Patient 2 showed that there were very low concentrations of TTO in the shampoo and \u201cvirtually undetectable\u201d amounts in the hair gel.<span id=\"d2171fe4-b9b3-4209-912f-8fd8fc8ae54f\" class=\"jrnlBibRef\" data-citation-string=\" R40 \"><sup id=\"bb8b641e-6190-48fc-83a2-d53b58ab8e3b\">40<\/sup><\/span>\u00a0The drops containing \u201c<em id=\"1f0d028e-9a72-4d09-a7f7-453f2ae2fa3b\">Melaleuca alternifolia<\/em>\u00a0extract\u201d added to the shampoo of a nine-year-old boy with gynecomastia (Patient 4 in<em>\u00a0<span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>) were not analyzed. However, as previously stated, although TTO does have estrogenic activity\u00a0<em id=\"95373dcc-d776-4054-82f0-6d2c8745427d\">in vitro<\/em>, the three penetrable constituents of TTO (terpinen-4-ol, \u03b1-terpineol, and eucalyptol) did not show any positive estrogenic activity when tested\u00a0<em id=\"d129fe08-07e7-4c5d-80df-eba284fd8358\">in vitro<\/em>\u00a0alone.<span id=\"a278c3a3-3557-41d3-9322-1fef623458d9\" class=\"jrnlBibRef\" data-citation-string=\" R22 \"><sup id=\"b1e94a6b-882d-41d1-a527-57081c1e5aed\">22<\/sup><\/span><\/p>\n<p id=\"c38d57c2-525e-4925-8633-f47cfd1349e2\" class=\"jrnlSecPara\">Another criticism of the studies associating LO and\/or TTO to prepubertal breast development relates to the extrapolation of the\u00a0<em id=\"722dd360-48a7-4bd0-922f-33cb2b7db95a\">in vitro<\/em>\u00a0results to the\u00a0<em id=\"cac8676b-7c18-4c24-9e48-526bad533ec3\">in vivo<\/em>\u00a0situation. It was noted that in the Henley et al. studies, 600,000 to 1.4 million times more LO or TTO was needed to elicit the same effect as 1 nM of E<sub id=\"7ab443e2-07f2-40f0-85c8-617f2f4a383a\">2<\/sub>, which served as the positive control, and it was calculated that a 20 kg child would have to use about 40 bottles of TTO-containing shampoo for each application.<span id=\"b6690246-811d-423c-a1e3-7e5a7d8169a9\" class=\"jrnlBibRef\" data-citation-string=\" R41 R42 \"><sup id=\"768dcbee-23e9-41e8-a004-b4235f41a6e9\">41,42<\/sup><\/span>\u00a0In addition, because of the limited amount of time that some of the products, such as shampoos, have skin contact before being washed off, the limited transdermal passage of many of the compounds in the products which reduces bioavailability, the lack of\u00a0<em id=\"174b40fe-0081-4ce6-a582-287427315779\">in vivo<\/em>\u00a0estrogenic activity in several studies, the volatile nature of EOs, and the possibility of exposure to other endocrine-disrupting chemicals contaminating the preparations such as chlorpyrifos, has led many authors to question the association.<span id=\"425d5335-39df-4f60-b0d3-629077ec1592\" class=\"jrnlBibRef\" data-citation-string=\" R15 R21 R23 R26 R27 R40 R42 \"><sup id=\"9c0acde5-85af-41a8-a522-910925af657d\">15,21,23,26,27,40,42<\/sup><\/span><\/p>\n<p id=\"690b7c47-4e3f-4386-ae53-3800dd58e2df\" class=\"jrnlSecPara\">The 12 patients summarized in\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T2 \">Table 2<\/span><\/em>\u00a0represented uncontrolled small case series or anecdotal reports. There is an additional anecdotal report of an 8-year-old girl with a 6-month history of precocious puberty, who had used LO hair spray for 6 months before the onset of pubertal development, but there was no notation as to whether the pubertal manifestations regressed after discontinuing the hair spray.<span id=\"8b8c3377-b237-4754-b6b6-7df7900a7c43\" class=\"jrnlBibRef\" data-citation-string=\" R45 \"><sup id=\"89cdb389-e646-45eb-986a-26c572079d76\">45<\/sup><\/span>\u00a0Hawkins and associates looked at the issue with an epidemiological approach. They initially noted that, after adjusting for a range of factors, the prevalence of prepubertal gynaecomastia had remained stable, while sales of TTO and LO have increased. One would expect to have seen a parallel increase in gynaecomastia and premature thelarche. This group conducted a cross-sectional study of children aged 2\u201315 years old in the United States recruited from an email database of the Franklin Health Research Center, social media and physicians\u2019 offices. One of the inclusion criteria was that the patients (or their parents on their behalf) self-identified as users of natural personal care products. The participants filled out the Aromatic Plant Ingredients and Child Health Survey online. The primary outcomes were the self-report of a diagnosis of prepubertal gynaecomastia (the term included both gynaecomastia and premature thelarche) or precocious puberty, as well as delayed puberty, diabetes, thyroid conditions, Cushing syndrome, hypopituitarism or growth hormone deficiency. They recruited 556 children with a mean age of 6.33 years, of whom 86% were white and 54.8% were male. Almost three-quarters of the respondents had been exposed to LO and\/or TTO. In this group, nine patients had an endocrine-related disorder: precocious puberty (n=2), delayed puberty (n=1), hypothyroidism (n=4), and growth hormone deficiency (n=1). None had a diagnosis of prepubertal gynaecomastia. They stated that there was no difference in the prevalence of the nine endocrine disorders versus that expected in the general population. They concluded that there is no relationship with endocrine disruption and the use of LO or TTO.<span id=\"b6f7b698-8dde-48ff-aff6-b67a770698f3\" class=\"jrnlBibRef\" data-citation-string=\" R43 \"><sup id=\"a0f5154f-8060-450e-8fa1-3a0d619897ea\">43<\/sup><\/span>\u00a0As acknowledged by the authors, this type of study has potential issues with both recall and selection bias.<\/p>\n<h1 id=\"77fc93e2-fd00-43e3-a6d6-b3736e236b4c\" class=\"jrnlHead1\">What is the strength of the putative association between prepubertal gynaecomastia and premature thelarche and the use of LO and\/or TTO?<\/h1>\n<p id=\"d741c678-7da3-4a69-a489-90e534a7eed5\" class=\"jrnlSecPara\">As emphasized by Hennekens and DeMets, \u201cCausation is a judgement based on the totality of evidence that includes several positive criteria\u201d.<span id=\"349f4aa4-56cd-4a7e-9e38-3ec10ce21e02\" class=\"jrnlBibRef\" data-citation-string=\" R46 \"><sup id=\"b8431ec9-c8ab-436f-a803-320434cfe50d\">46<\/sup><\/span>\u00a0These criteria were described in a classic paper by Sir Austin Bradford Hill in 1965.<span id=\"fcf06e9b-85c3-46a3-b978-9946e148032d\" class=\"jrnlBibRef\" data-citation-string=\" R7 \"><sup id=\"7e14f61a-e3d2-4c2a-9c82-559c1ca70088\">7<\/sup><\/span>\u00a0The first, and most important, is the\u00a0<em id=\"68e9a9f8-d76c-4e3e-8fd2-e19926f7bbe6\" class=\"sty cts-9\">strength of the association<\/em>. Is exposure to LO and\/or TTO associated with a relatively large increase in prepubertal gynecomastia or premature thelarche after confounding factors are removed? Second is\u00a0<span id=\"7c2e15ea-5dee-4341-8610-3fd6627be8a1\" class=\"styrm cts-7\"><em id=\"32ba42ff-0054-4019-b4ec-e222bd1d048f\" class=\"sty cts-9\">consistency<\/em><\/span>; has the association been repeatedly observed by others in different settings and over time? Third is\u00a0<span id=\"6d234149-75b5-4fd8-bb60-98215445124b\" class=\"styrm cts-7\"><em id=\"d7f37fbb-f509-43d2-8842-3b76b9131c45\" class=\"sty cts-9\">specificity<\/em><\/span>\u00a0between the exposure and the effect, realizing that the effect (e.g. prepubertal gynaecomastia) may have many causes. The fourth is\u00a0<span id=\"14ed2efd-6fb8-40c9-a2f9-c8438d7b433f\" class=\"styrm cts-7\"><em id=\"ca5ab0f3-69e9-4102-947e-25845f04433d\" class=\"sty cts-9\">temporality<\/em><\/span>. When dealing with endocrine disruptive agents, the effect or disease must occur or worsen after the exposure and not before, realizing that the exposure may occur years before the condition becomes clinically manifest. Prepubertal gynaecomastia or thelarche should appear after exposure to LO or TTO. Also, for reversible conditions, such as gynaecomastia, the condition should improve or remit after the exposure to the inciting agent is removed. Hill\u2019s fifth criterion is the presence of a\u00a0<em id=\"cac5be73-5a61-4a38-86fa-c4977ca721fc\" class=\"sty cts-9\">biological gradient<\/em>, or dose-response curve. Does the incidence of the condition rise with increased exposure? The sixth is\u00a0<span id=\"8d542eca-5ee7-4b64-af82-dc8f9efbb796\" class=\"styrm cts-7\"><em id=\"6f43b594-3565-4fe2-b1fd-5abb25146305\" class=\"sty cts-9\">plausibility<\/em><\/span>. In this case, is it biologically plausible that exposure to LO and TTO could cause premature breast development? The seventh criterion is\u00a0<span id=\"b509a9d6-0206-4ce4-80b3-37999f501082\" class=\"styrm cts-7\"><em id=\"678a52af-4de9-476f-9bb9-09dad79311b4\" class=\"sty cts-9\">coherence<\/em><\/span>. Does the incidence of prepubertal breast glandular tissue development increase in parallel to the use of LO and\/or TTO products by children?\u00a0<span id=\"782622ea-ffea-4269-81a5-d357bae5d12d\" class=\"styrm cts-7\"><em id=\"4b8f1b29-9736-4c38-b767-8b9942d2cff5\" class=\"sty cts-9\">Experiment<\/em><\/span>\u00a0is Hill\u2019s eighth criterion. Ideally, such experimentation would be a randomized, double-blind, placebo-controlled trial of a large group of children exposed to either LO and\/or TTO containing skincare products or shampoo or identical products without LO or TTO to compare the incidence of prepubertal gynecomastia or premature thelarche. Serial measurements of testosterone and E<sub id=\"9e5ec4f3-5206-44dc-a9c8-64b485f540f8\">2<\/sub>, as well as serum levels of the LO and TTO metabolites, should be performed to see if clinically relevant concentrations of bioactive LO and TTO metabolites are reached and whether there are antiandrogenic effects or alterations in aromatase activity. Short of that, animal experimentation could lend support if the species chosen responds to the stimulus similar to humans. Hill\u2019s final criterion is\u00a0<em id=\"f80247f8-7b38-4a5c-9f90-46fab785fc5e\">analogy<\/em>. Is there evidence that prepubertal gynecomastia or thelarche can occur from other environmental exposures?\u00a0<em><span class=\"jrnlTblRef\" data-citation-string=\" T3 \">Table 3<\/span><\/em>\u00a0summarizes our scorecard for the association between LO and TTO and prepubertal gynecomastia or premature thelarche.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-67522\" src=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3.png\" alt=\"\" width=\"1049\" height=\"1063\" srcset=\"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3.png 1049w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3-296x300.png 296w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3-1011x1024.png 1011w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3-768x778.png 768w, https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/Are-Prepubertal...-Table-3-592x600.png 592w\" sizes=\"auto, (max-width: 1049px) 100vw, 1049px\" \/><\/p>\n<div id=\"26fa9a06-971e-47b5-96a2-c48a9e30709e\" class=\"jrnlTblBlock\">\n<div id=\"8684c0bf-4c18-478c-9a0c-3b761cd12ad9\" class=\"jrnlTblFootGroup\">\n<div id=\"cd2e1b27-45a8-438b-9324-2de041f89ccf\" class=\"jrnlTblFoot\">\n<p class=\"jrnlTblFootText\">In summary, in applying the Hill criteria, we find that there is insufficient evidence to support a link between the use of LO or TTO products and the occurrence of prepubertal gynaecomastia or premature thelarche. We acknowledge that there is biological plausibility from the <em id=\"34d5dbac-6d17-472b-9b90-923c148297f7\">in vitro<\/em>\u00a0studies and that there is a temporal relationship between the use of these products and the onset of premature thelarche or prepubertal gynaecomastia in the 12 cases that have been reported in detail to date. However, the issues about the duration of exposure, the actual dermal absorption of the oestrogen agonist or androgen antagonist components of LO and TTO, the possibility of contamination of some of the products with oestrogenic substances, and the lack of unbiased, non-anecdotal human experimental results has led us to conclude that LO and TTO have not been shown to be associated with the clinical development of premature breast enlargement, and that the strength of association is very weak.<\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Article highlights Lavender and tree tea oils have\u00a0in vitro\u00a0oestrogenic and antiandrogenic activity. It has been postulated that these oils may cause prepubertal gynaecomastia and premature thelarche. The association is based on a small number patients (N=12) described in five publications. Based upon the amount of dermal penetration of the oils or their constituents and the [&hellip;]<\/p>\n","protected":false},"author":100365,"featured_media":60977,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","rank_math_lock_modified_date":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-60927","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","vocabulary_1-pediatric-endocrinology"],"acf":{"wpcf-article_introduction":"","wpcf-article_abstract":"Various studies, conducted since 2007, have reported a total of eight boys with prepubertal gynaecomastia and four girls with premature thelarche following exposure to lavender and\/or tree tea oil. All patients experienced regression of the breast tissue after they stopped using these oils. Both of these essential oils, and several of their constituents, have oestrogenic and antiandrogenic activity <em id=\"d8aa5072-6b9f-4209-99bc-1a16f8a69e45\">in vitro<\/em>. However, limited dermal penetration of some of the components means that the\u00a0<em id=\"738f9845-14dc-471e-8d99-64051d826b6d\">in vitro<\/em>\u00a0findings cannot be extrapolated to the\u00a0<em id=\"6b8916cc-90cf-4213-be94-9e998e40c60a\">in vivo<\/em>\u00a0situation. There are unanswered questions as to how much lavender or tea tree oil was actually present in the skincare products used by the children and a lack of information about exposure to other agents. Furthermore, since both prepubertal gynaecomastia and premature thelarche often spontaneously regress, it cannot be concluded that the use of lavender and\/or tree tea oil is the cause of the gynaecomastia and thelarche in these children.","wpcf-article_keywords":"<span id=\"931654e8-3b66-449e-a248-7ac811f90e3c\" class=\"jrnlKeyword\">Gynaecomastia<\/span>,\u00a0<span id=\"43f82616-9170-4779-864e-8fd495aaec9b\" class=\"jrnlKeyword\">premature thelarche<\/span>,\u00a0<span id=\"ca224036-470a-40a9-b4ce-bcac107a78bf\" class=\"jrnlKeyword\">essential oils<\/span>,\u00a0<span id=\"722cd627-1175-4926-9c66-45d3dced8cb2\" class=\"jrnlKeyword\">lavender oil<\/span>,\u00a0<span id=\"f51b2375-375b-48f8-9d0b-660b051df0b3\" class=\"jrnlKeyword\">tea tree oil<\/span>,\u00a0<span id=\"b40d7751-5aca-4caf-89cc-82eac0308db8\" class=\"jrnlKeyword\">endocrine disrupting chemicals<\/span>.","wpcf-article_citation_override":"<i>touchREVIEWS in Endocrinology<\/i>. 2023;19(2):60-68","wpcf-compliance-with-ethics":"This article involves a review of the literature and does not report new clinical data, and does not involve any studies with human or animal subjects performed by any of the authors.","wpcf-article_disclosure":"Glenn Braunstein has been a defence expert for Johnson &amp; Johnson in litigation involving risperidone allegedly causing gynaecomastia.\u00a0<span id=\"7a4b4d60-eccd-4411-858d-a38374871979\">Elsa Braunstein has no financial or non-financial relationships or activities to declare in relation to this article.<\/span>","wpcf-review_process":"Double-blind peer review.","wpcf-authorship":"The named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.","wpcf-article_correspondence":"<span id=\"dfd33afb-17b0-4588-aad5-2ac5a3cc3bfe\" class=\"jrnlAuthor\"><span class=\"jrnlGivenName\">Glenn D<\/span>\u00a0<span class=\"jrnlSurName\">Braunstein<\/span><\/span>,\u00a0<span id=\"c2ff80ea-cb71-4ea6-8a87-8ea4a7a22083\" class=\"jrnlCorAddress\"><span id=\"b1cdd798-3837-4a35-94e5-e44157f4899b\" class=\"jrnlDepartment\">Department of Medicine<\/span>,\u00a0<span id=\"51d2088a-9594-4af0-a630-76d7b2e40e27\" class=\"jrnlInstitution\">Cedars-Sinai Medical Center<\/span>,\u00a0<span id=\"f32fc25f-975c-498a-b393-d0ccc69459e3\" class=\"jrnlCity\">Los Angeles<\/span>,\u00a0<span id=\"3b3f50b1-0992-4cef-9d8d-e924f787b133\" class=\"jrnlState\">CA 90048<\/span>, <span id=\"47172de0-9b9c-49c3-a8fe-c12b8d835939\" class=\"jrnlCountry\">USA<\/span><\/span>; <span id=\"4cc9cec2-dbc1-4e75-b5a2-0a0b93d21eb5\" class=\"jrnlEmail\">glenn.braunstein@cshs.org<\/span>","wpcf-article_support":"No funding was received in the publication of this article.","wpcf-open_access":"This article is freely accessible at touchENDOCRINOLOGY.com \u00a9 Touch Medical Media 2023.","wpcf-article_pdf":"https:\/\/touchendocrinology.com\/wp-content\/uploads\/sites\/5\/2023\/09\/touchENDOCRINOLOGY_19.2_pp60-68.pdf","wpcf-article_pdf-gated":true,"wpcf-article_doi":"<a href=\"http:\/\/doi.org\/10.17925\/EE.2023.19.2.9\">http:\/\/doi.org\/10.17925\/EE.2023.19.2.9<\/a>","wpcf-old_nid":"","wpcf-article_image":"","wpcf-editor_choice":false,"wpcf-old_author_ids":"","wpcf-article_references":"<p id=\"R1\" class=\"jrnlRefText\"><span class=\"RefSlNo\">1.<\/span>\u00a0<span id=\"05810bb7-8b30-42a3-a9f0-b4e144448585\" class=\"RefAuthor\"><span id=\"4c465106-50b5-4d4d-bdda-cb3074720f9e\" class=\"RefSurName\">Henley<\/span>\u00a0<span id=\"b0ea3fc9-8a0a-4cd7-8841-45064ad12651\" class=\"RefGivenName\">DV<\/span><\/span>,\u00a0<span id=\"88f9d0e2-4b0e-49f4-8520-a83dc52dd031\" class=\"RefAuthor\"><span id=\"6c26a4ac-8f60-4e4c-8c59-30fdf4a2b87b\" class=\"RefSurName\">Lipson<\/span>\u00a0<span id=\"079228fe-c241-4609-bfc7-7e60aa4d66c0\" class=\"RefGivenName\">N<\/span><\/span>,\u00a0<span id=\"523b38d5-c5c0-4d0a-8c40-36700c91c6e1\" class=\"RefAuthor\"><span id=\"75c88c50-207e-485b-aff6-3425f1cd70b6\" class=\"RefSurName\">Korach<\/span>\u00a0<span id=\"93f7490e-c9c7-4010-a446-5ca541743a87\" class=\"RefGivenName\">KS<\/span><\/span>,\u00a0<span id=\"10afcf9e-4207-4452-9da2-8c61b75b41aa\" class=\"RefAuthor\"><span id=\"4c7e49e3-8a8e-4da2-8099-cdeaad4803f4\" class=\"RefSurName\">Bloch<\/span>\u00a0<span id=\"ff4cb544-2ef8-4d71-aa1e-0537d24924d6\" class=\"RefGivenName\">CA<\/span><\/span>.\u00a0<span id=\"45ab55c0-5bdc-4efa-982f-bdfef81583a4\" class=\"RefArticleTitle\">Prepubertal gynecomastia linked to lavender and tea tree oils<\/span>.\u00a0<span id=\"a8995a9b-5fb4-4ece-b890-30d073898729\" class=\"RefJournalTitle\"><em id=\"655ecdda-4504-4805-8b64-6e4d620db886\">N Engl J Med<\/em><\/span>.\u00a0<span id=\"a48ecd14-a74c-4761-b157-ef4d0b97478c\" class=\"RefYear\">2007<\/span>;<span 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id=\"R4\" class=\"jrnlRefText\"><span class=\"RefSlNo\">4.<\/span>\u00a0<span id=\"614b62e1-a7e8-4e56-8280-dcd24aeffdec\" class=\"RefAuthor\"><span id=\"856020ef-1424-421a-ad2f-3c972b0bb2fc\" class=\"RefSurName\">Braunstein<\/span>\u00a0<span id=\"6a446620-2662-4af6-a332-90624b23489a\" class=\"RefGivenName\">GD<\/span><\/span>, .\u00a0<span id=\"6965d250-18b8-4007-9cf8-518773e1d5c5\" class=\"RefArticleTitle\">Environmental gynecomastia<\/span>.\u00a0<span id=\"619ed3f3-a71a-4fa7-b084-3683a33ba192\" class=\"RefJournalTitle\"><em id=\"5f516f24-4af4-4c15-a762-3a6ffc9ddd8b\">Endocr Pract<\/em><\/span>.\u00a0<span id=\"d4d4a975-339e-4550-b319-a5f8a09a91fd\" class=\"RefYear\">2008<\/span>;<span id=\"c8cf7093-5672-4fea-9f88-b1e1e84ca1de\" class=\"RefVolume\">14<\/span>:<span id=\"d69ff3e1-6714-42e7-b316-244e137c6701\" class=\"RefFPage\">409<\/span>\u2013<span id=\"0ee666d2-7df2-4406-954b-de690f679d49\" class=\"RefLPage\">11<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>:\u00a0<span 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id=\"32622a8c-237a-4202-b819-c26c34f89b16\" class=\"RefAuthor\"><span id=\"d68517dc-6bab-452d-951f-701c99ff5986\" class=\"RefSurName\">Lazar <\/span><span id=\"024a586e-9a46-41ad-b034-e310de51fc84\" class=\"RefGivenName\">L<\/span><\/span>. <span id=\"ddb1fbdb-74cb-40fa-b0bb-c99342ddc3ef\" class=\"RefArticleTitle\">Prepubertal gynaecomastia: Aetiology, course, and outcome<\/span>.\u00a0<span id=\"ff34e71a-2cb6-4dee-973c-94b8a239ceb1\" class=\"RefJournalTitle\"><em id=\"93e736fd-7cfb-4267-9e48-97ef4c56a72a\">Clin Endocrinol (Oxf)<\/em><\/span>.\u00a0<span id=\"6ca6c964-80a1-44be-8cd3-976bb2eb2e5c\" class=\"RefYear\">2004<\/span>;<span id=\"49df29d7-f590-4ff5-8455-78dd1fe798f1\" class=\"RefVolume\">61<\/span>:<span id=\"02b2f929-477f-4f6a-8178-a1904529b590\" class=\"RefFPage\">55<\/span>\u2013<span id=\"190eebb4-b4e7-437e-be4f-e770f171ad06\" class=\"RefLPage\">60<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>: <span id=\"71658b3d-1482-4195-a138-04e1e0be98b0\" class=\"RefDOI\">10.1111\/j.1365-2265.2004.02059.x<\/span>.<\/p>\r\n<p id=\"R6\" class=\"jrnlRefText\"><span class=\"RefSlNo\">6.<\/span>\u00a0<span id=\"1dbcf9cc-72b5-488e-91c4-460618aacc3b\" class=\"RefAuthor\"><span id=\"6c0e7393-783b-4bb8-9946-4fa88276bf84\" class=\"RefSurName\">Zhang<\/span>\u00a0<span id=\"1ffe2acb-f636-40be-b73f-b6e68631f779\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"beb46014-3932-440c-8ae4-4ab101064a79\" class=\"RefAuthor\"><span id=\"a6ef9d28-fdf3-470b-8fb1-464d33ebdaac\" class=\"RefSurName\">Xu<\/span>\u00a0<span id=\"629ac235-384a-48a7-bb62-4a351f430dc5\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"0e4e192d-9465-4637-beed-fb3a2680aacd\" class=\"RefAuthor\"><span id=\"039fe05b-b8d6-408b-80bc-eef7a32aed6b\" class=\"RefSurName\">Liu<\/span>\u00a0<span id=\"03d5d278-3f35-4c23-86cb-1e4054f7ca6d\" class=\"RefGivenName\">L<\/span><\/span>,\u00a0<span id=\"7edd2d8d-2348-4dd7-8027-c89d50247f1b\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"40776846-a9aa-4fbb-9667-94aabc265a01\" class=\"RefArticleTitle\">The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China<\/span>. <span id=\"086e5cd3-a7ed-4911-ade7-5257f6e5b289\" class=\"RefJournalTitle\"><em id=\"1fd6421b-c306-4c03-93b5-5c8096fe94bd\">BMC Pediatr<\/em><\/span>. <span id=\"50f0e8b8-939d-4adb-9546-fe6968d3fb2f\" class=\"RefYear\">2019<\/span>;<span id=\"b6ec415d-2252-4d47-831f-a64be689a576\" class=\"RefVolume\">19<\/span>:<span id=\"1ac32acb-5689-4000-a360-41fb893c05dd\" class=\"RefFPage\">107<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"dec221c3-5d04-44a9-abbb-02dcaa0753a1\" class=\"RefDOI\">10.1186\/s12887-019-1426-6<\/span>.<\/p>\r\n<p id=\"R7\" class=\"jrnlRefText\"><span id=\"c3e2f1a5-5ae9-4c61-a6ae-b89c6a76e39b\" class=\"RefSlNo\">7.<\/span>\u00a0<span id=\"6a6f06b9-9f9c-4a38-ba28-52e60718ab30\" class=\"RefAuthor\"><span id=\"e5b4ebe9-5c08-410d-b6c1-9749e092a8a5\" class=\"RefSurName\">HILL<\/span>\u00a0<span id=\"00e53beb-a5de-4ead-a6fa-e5f7f832b495\" class=\"RefGivenName\">AB<\/span><\/span>.\u00a0<span id=\"d8200d95-9549-4216-b228-bdd3f41e489c\" class=\"RefArticleTitle\">The environment and disease: Association or causation<\/span>\u00a0<span id=\"6bbb597d-f195-4eb4-a51a-93226ab3fd15\" class=\"RefJournalTitle\"><em id=\"95d27acb-eb1f-498d-adb8-d9fef6638cd3\">Proc R Soc Med<\/em><\/span>.\u00a0<span id=\"f296ca5f-11f6-4b98-a672-181c79cb2966\" class=\"RefYear\">1965<\/span>;<span id=\"c5cbcfee-4de2-455f-a4e1-082a06d4d97d\" class=\"RefVolume\">58<\/span>:<span id=\"b79ad353-a817-47b6-b2a4-8abb6537c30d\" class=\"RefFPage\">295<\/span>\u2013<span id=\"917eb382-81a1-492c-a308-a7c33b36d916\" class=\"RefLPage\">300<\/span>.<\/p>\r\n<p id=\"R8\" class=\"jrnlRefText\"><span id=\"85033d68-81f9-47aa-aeba-b5467f9909b8\" class=\"RefSlNo\">8.<\/span>\u00a0<span id=\"f20106f2-60af-4c4f-8273-c815b12b46b5\" class=\"RefAuthor\"><span id=\"f1e7fced-629a-45f3-9413-365f04dfe6d9\" class=\"RefSurName\">Cavanagh<\/span>\u00a0<span id=\"3a02d027-6c1f-4819-8838-a306953c4aa9\" class=\"RefGivenName\">HMA<\/span><\/span>,\u00a0<span id=\"2ed3ad5b-9289-489b-b40f-982cce7003ba\" class=\"RefAuthor\"><span id=\"5e0d923b-409c-4fe1-a592-0d496b73ba0b\" class=\"RefSurName\">Wilkinson<\/span>\u00a0<span id=\"374cb014-5d8c-4747-a51e-438ee3934b22\" class=\"RefGivenName\">JM<\/span><\/span>.\u00a0<span id=\"a79c7382-4e73-4f22-96ea-4d558106fed8\" class=\"RefArticleTitle\">Biological activities of lavender essential oil<\/span>. <span id=\"987c0fa2-a742-4af4-9bba-f11fc778aa70\" class=\"RefJournalTitle\"><em id=\"88399c5e-a75e-4a0c-9e3a-18396a99c8a5\">Phytother Res<\/em><\/span>. <span id=\"8eec9e43-4c90-4ee2-ba67-2b151a126c3e\" class=\"RefYear\">2002<\/span>;<span id=\"3f75d695-63d2-4094-8559-bba4698d4350\" class=\"RefVolume\">16<\/span>:<span id=\"f911c41e-7aea-4e85-9c35-be70b094dcb9\" class=\"RefFPage\">301<\/span>\u2013<span id=\"1be521ff-e5e9-4bd9-92b7-fe16323b3323\" class=\"RefLPage\">8<\/span>. <span id=\"d07f154b-e4f5-484a-b4ed-31f5e973d33c\" class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"07b5cc83-29e3-4d81-a47b-3f3190c8ced7\" class=\"RefDOI\">10.1002\/ptr.1103<\/span>.<\/p>\r\n<p id=\"R9\" class=\"jrnlRefText\"><span class=\"RefSlNo\">9.<\/span>\u00a0<span id=\"204021a3-15ea-4b18-8397-2469cfcbfd4e\" class=\"RefAuthor\"><span id=\"40bd4c2f-6340-4d36-9bf5-2fc3d64b59f8\" class=\"RefSurName\">Jager<\/span>\u00a0<span id=\"c2d0a911-25ac-4b2d-89a3-3e68083b9ed7\" class=\"RefGivenName\">W<\/span><\/span>,\u00a0<span id=\"5eb00307-e72b-45f1-9ffa-738310ae14fa\" class=\"RefAuthor\"><span id=\"289322df-9057-4045-80f7-7df15614477f\" class=\"RefSurName\">Buchbauer<\/span>\u00a0<span id=\"0d193de1-11c7-42ab-956f-39accb40fc12\" class=\"RefGivenName\">G<\/span><\/span>,\u00a0<span id=\"b286d691-9277-444a-a2e3-f81a39362be7\" class=\"RefAuthor\"><span id=\"f9eb64b4-2b46-4a05-8fba-5275f4e4041d\" class=\"RefSurName\">Jirovetz<\/span>\u00a0<span id=\"5684b972-afb7-44bf-8302-5a05712d058e\" class=\"RefGivenName\">L<\/span><\/span>,\u00a0<span id=\"2ee74ad0-58ca-46a2-981a-1964a252a61e\" class=\"RefAuthor\"><span id=\"2f01b158-f4d2-4046-8b9f-6108d6861232\" class=\"RefSurName\">Fritzer<\/span>\u00a0<span id=\"e47e650c-a2e0-47ba-8ba9-d039d2cec115\" class=\"RefGivenName\">M<\/span><\/span>.\u00a0<span id=\"c5bd04f1-83f1-4947-832f-c9b5dc48954b\" class=\"RefArticleTitle\">Percutaneous absorption of lavender oil from a massage oil<\/span>.\u00a0<span id=\"ca0dfb2f-2848-4cd1-a22c-ba0e565626bb\" class=\"RefJournalTitle\"><em id=\"27f2da2b-6bac-4909-baa5-f9e593cc7745\">J Soc Cosmetic Chem<\/em><\/span>.\u00a0<span id=\"2c84b7eb-44e1-458e-a47f-dcc1b0fb37f2\" class=\"RefYear\">1992<\/span>;<span id=\"87d13059-b596-4798-855e-ec52895dc551\" class=\"RefVolume\">43<\/span>:<span id=\"be9812b6-b46b-482e-8505-11274a361731\" class=\"RefFPage\">49<\/span>\u2013<span id=\"7b3c898c-04aa-4dc3-88c1-6517b1cbeec0\" class=\"RefLPage\">54<\/span>.<\/p>\r\n<p id=\"R10\" class=\"jrnlRefText\"><span class=\"RefSlNo\">10.<\/span>\u00a0<span id=\"c56d8b08-5ff4-4838-a7ae-52e72b28e16c\" class=\"RefCollaboration\">Scientific Committee on Consumer Products<\/span>.\u00a0<span id=\"f60ff6e5-6fbf-44fd-b6c0-6e9c9ff96f5e\" class=\"RefArticleTitle\">Opinion on tea tree oil<\/span>.\u00a0<span id=\"9bde57d8-4375-4977-97ac-4181fd370724\" class=\"RefYear\">2008<\/span>. <span class=\"RefComments\">Available at<\/span>: <span id=\"0c7c4033-6379-4b07-b7d3-f69befe04bda\" class=\"RefWebSite\"><a href=\"http:\/\/ec.europa.ed\/health\/ph_risk\/risk_en.htm\">http:\/\/ec.europa.ed\/health\/ph_risk\/risk_en.htm<\/a><\/span>.<\/p>\r\n<p id=\"R11\" class=\"jrnlRefText\"><span class=\"RefSlNo\">11.<\/span>\u00a0<span id=\"e436149c-5eb5-4d7c-b155-8df3ddbaaac6\" class=\"RefAuthor\"><span id=\"9f325c69-bd4e-4da4-bddb-5614816ab108\" class=\"RefSurName\">Nielsen<\/span>\u00a0<span id=\"0732a9f2-da1c-4c12-b795-b30aa13a334b\" class=\"RefGivenName\">JB<\/span><\/span>,\u00a0<span id=\"f8f9f3b9-d69c-423f-93af-14fe6473842e\" class=\"RefAuthor\"><span id=\"60bb22d6-62a8-4972-aa0f-bd3171650500\" class=\"RefSurName\">Nielsen<\/span>\u00a0<span id=\"cf1bd64f-6d2d-40e9-9d74-414371d6eb90\" class=\"RefGivenName\">F<\/span><\/span>.\u00a0<span id=\"b5e81a6a-1e14-4724-aa3b-a92ac4767959\" class=\"RefArticleTitle\">Topical use of tea tree oil reduces the dermal absorption of benzoic acid and methiocarb<\/span>.\u00a0<span id=\"d3459c29-8d4f-44e0-9fc9-e250c9bfd90b\" class=\"RefJournalTitle\"><em id=\"3648f7c0-ad5d-4b1c-b1b1-c6c404c3a19c\">Arch Dermatol Res<\/em><\/span>.\u00a0<span id=\"bbaa7d9d-91c6-42e2-91e8-68169733d345\" class=\"RefYear\">2006<\/span>;<span id=\"479cbb04-74af-45e7-9490-1a5a0581e6bc\" class=\"RefVolume\">297<\/span>:<span id=\"7fc90934-a0e7-4f37-96c8-81fdd3ba3338\" class=\"RefFPage\">395<\/span>\u2013<span id=\"8554deb5-582e-48bc-875f-7207020ec1e1\" class=\"RefLPage\">402<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>: <span id=\"7853e738-5fe4-4bca-982a-09ab4ea19e54\" class=\"RefDOI\">10.1007\/s00403-005-0627-z<\/span>.<\/p>\r\n<p id=\"R12\" class=\"jrnlRefText\"><span id=\"c07a22ae-3617-4d89-8189-74e32d72062f\" class=\"RefSlNo\">12.<\/span>\u00a0<span id=\"d49b819d-51e4-4ebc-9237-c2333661a81b\" class=\"RefAuthor\"><span id=\"be2fef9f-0fdc-4e55-b345-2f05f1a751fc\" class=\"RefSurName\">Ramsey<\/span>\u00a0<span id=\"7ec29f33-c1a4-4036-a666-240a89193220\" class=\"RefGivenName\">JT<\/span><\/span>,\u00a0<span id=\"bd0a0d23-8881-40bb-80dd-3454184e7e3c\" class=\"RefAuthor\"><span id=\"e20255c8-4084-4696-a568-39e3f3dbdca2\" class=\"RefSurName\">Shropshire<\/span>\u00a0<span id=\"f2aa1a21-91eb-41f0-a6c5-36dd5a717474\" class=\"RefGivenName\">BC<\/span><\/span>,\u00a0<span id=\"a84cf725-71a2-4c7b-ae80-29d1e16d7f3f\" class=\"RefAuthor\"><span id=\"f456392d-1669-4262-a36c-03a4ce5bdafb\" class=\"RefSurName\">Nagy<\/span>\u00a0<span id=\"c0eeebbf-5b4c-457f-8521-fa995b3c33ce\" class=\"RefGivenName\">TR<\/span><\/span>,\u00a0<span id=\"9cd20ab9-0bb2-4a97-9f05-d4d641714351\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"8a6eb28a-49d3-4967-a84a-23c81060e2a5\" class=\"RefArticleTitle\">Essential oils and health<\/span>.\u00a0<span id=\"240a9049-a177-4f10-a67a-55bbe51ec5ea\" class=\"RefJournalTitle\"><em id=\"8199a7ef-06df-4336-8491-4f59b236824c\">Yale J Biol Med<\/em><\/span>.\u00a0<span id=\"97c56f31-7fb8-42d7-afec-7a2c0a2c6c7e\" class=\"RefYear\">2020<\/span>;<span id=\"cae1c24b-3a8e-4585-9596-2b1d7feb5725\" class=\"RefVolume\">93<\/span>:<span id=\"fc009a1d-daaa-41dc-89bf-fa8d47a11e41\" class=\"RefFPage\">291<\/span>\u2013<span id=\"56d7eabc-9ee7-4218-aff0-46bbd6dd976a\" class=\"RefLPage\">305<\/span>.<\/p>\r\n<p id=\"R13\" class=\"jrnlRefText\"><span class=\"RefSlNo\">13.<\/span>\u00a0<span id=\"d5283f6d-a292-44da-ad3c-5bfb4156dd6e\" class=\"RefAuthor\"><span id=\"b6e6964e-5d23-4154-8029-8d30fbe2dc42\" class=\"RefSurName\">Giroux<\/span>\u00a0<span id=\"1b7c1a8f-3063-44a2-b24e-98be60cc6ac2\" class=\"RefGivenName\">J-M<\/span><\/span>,\u00a0<span id=\"f2eadf96-2951-4f55-8616-54a55a477917\" class=\"RefAuthor\"><span id=\"db76c371-a4f7-46ef-8b8d-e71b89a28da6\" class=\"RefSurName\">Orjubin<\/span>\u00a0<span id=\"f82a1881-58d3-47e5-be15-2fb8448d4aa1\" class=\"RefGivenName\">M<\/span><\/span>.\u00a0<span id=\"5b453250-cfad-42a9-b3e0-4a16ba894754\" class=\"RefArticleTitle\">\u201cLavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities\u201d. <\/span><span id=\"405ce3f6-eeb9-4209-8a12-09c071d8aef5\" class=\"RefJournalTitle\"><em id=\"b74dc435-985b-44ca-b655-9d34f41da10a\">J Clin Endocrinol Metab<\/em><\/span>. <span id=\"659ed6d0-360f-4a22-acc7-2312c5ff084d\" class=\"RefYear\">2020<\/span>;<span id=\"4934ec21-14c2-4291-b6a0-ef8d4df36147\" class=\"RefVolume\">105<\/span>:<span id=\"6f458469-77c4-4787-b54e-7d2c689aa2ee\" class=\"RefFPage\">e2677<\/span>\u2013<span id=\"b589226d-c497-47e0-a0fd-73c9c2729609\" class=\"RefLPage\">8<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"722d544a-7ee9-4686-a471-7e875d892997\" class=\"RefDOI\">10.1210\/clinem\/dgaa226<\/span>.<\/p>\r\n<p id=\"R14\" class=\"jrnlRefText\"><span class=\"RefSlNo\">14.<\/span>\u00a0<span id=\"5bfb035b-ca3f-4356-af67-a958f268c96c\" class=\"RefAuthor\"><span id=\"a69668a8-6879-47ea-9fd1-96bcdf8e670a\" class=\"RefSurName\">Larkman<\/span>\u00a0<span id=\"3768a7b6-566b-473c-85b4-f8bae49aa60b\" class=\"RefGivenName\">T<\/span><\/span>.\u00a0<span id=\"b1608001-3b46-46d2-b762-61348d7e7a00\" class=\"RefArticleTitle\">Letter to the editor: \u201cLetter to the editor: \u201cLavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities\u201d<\/span>. <span id=\"a87ace57-7df2-4042-bd40-df043723ac5e\" class=\"RefJournalTitle\"><em id=\"4df948e1-d621-46d1-b03e-b071208d4a37\">J Clin Endocrinol Metab<\/em><\/span>.\u00a0<span id=\"f1602e7d-d5ef-483c-b118-d87eba9dafd8\" class=\"RefYear\">2020<\/span>;<span id=\"97882992-4f35-47d9-a3d1-d0d6088c7937\" class=\"RefVolume\">105<\/span>:<span id=\"c8b7e44c-0762-4062-bad0-57f69861148b\" class=\"RefELocation\">dgaa392<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"061e15e1-069c-443b-a2ce-fc27934a5f03\" class=\"RefDOI\">10.1210\/clinem\/dgaa392<\/span>.<\/p>\r\n<p id=\"R15\" class=\"jrnlRefText\"><span id=\"29c0914c-b5cd-4772-b7ca-0eb86eafff24\" class=\"RefSlNo\">15.<\/span>\u00a0<span id=\"6521697b-d441-437a-90ba-01394fa90c22\" class=\"RefAuthor\"><span id=\"27235209-bd71-4621-a522-924e757e21d3\" class=\"RefSurName\">Carson<\/span>\u00a0<span id=\"7595a777-b70a-41c7-b24f-5833a7b6b82b\" class=\"RefGivenName\">CF<\/span><\/span>,\u00a0<span id=\"ed1309b2-10b8-426e-8ab4-90ada1292428\" class=\"RefAuthor\"><span id=\"bfc8643f-3342-4549-ad8f-318a9b05163a\" class=\"RefSurName\">Tisserand<\/span>\u00a0<span id=\"b66602a5-c8e6-40cb-ac39-69005b1394aa\" class=\"RefGivenName\">R<\/span><\/span>,\u00a0<span id=\"ccaf3aad-5780-4ed4-a679-27dc4c7ac7f0\" class=\"RefAuthor\"><span id=\"8934ab9d-20fc-4a2a-b44a-fe3441be2ac8\" class=\"RefSurName\">Larkman<\/span>\u00a0<span id=\"182fa204-7cca-48b2-88d8-953df1fd48e0\" class=\"RefGivenName\">T<\/span><\/span>.\u00a0<span id=\"3a0708cd-0987-48ff-ab36-cae00fd2d9f6\" class=\"RefArticleTitle\">Lack of evidence that essential oils affect puberty<\/span>. <span id=\"565ef816-1827-4b73-b274-ea66b0f367c0\" class=\"RefJournalTitle\"><em id=\"9e89aad7-8830-42df-97a3-0be87df0679f\">Reproductive Toxicology<\/em><\/span>. <span id=\"58a6817a-3dd6-4f9d-8fda-8d1465abfc33\" class=\"RefYear\">2014<\/span>;<span id=\"217c3f70-74a5-4e79-b30e-a1de5acd6087\" class=\"RefVolume\">44<\/span>:<span id=\"754393da-ecbe-4d40-bef8-9a60084cf361\" class=\"RefFPage\">50<\/span>\u2013<span id=\"ef8b8ddf-d65c-4e2e-81e8-4b42bd770a80\" class=\"RefLPage\">1<\/span>. <span id=\"09c27c36-5a35-4ab4-9dc6-6ff26213778c\" class=\"RefComments\">DOI<\/span>: <span id=\"2f9e2a13-df0e-4046-8610-72eccfa1e1b5\" class=\"RefDOI\">10.1016\/j.reprotox.2013.09.010<\/span>.<\/p>\r\n<p id=\"R16\" class=\"jrnlRefText\"><span id=\"5337dc80-eaf9-46e7-8ae0-cc2ed2c3e61c\" class=\"RefSlNo\">16.<\/span>\u00a0<span id=\"bd3ff903-1d02-4f38-bcd5-bc6a441a21e0\" class=\"RefAuthor\"><span id=\"5984a19d-0676-4aa4-8a91-34c825f7b189\" class=\"RefSurName\">Monte<\/span>\u00a0<span id=\"756316c4-7e04-40f5-a4bd-e7cc80281b55\" class=\"RefGivenName\">WC<\/span><\/span>,\u00a0<span id=\"25055548-65c1-4cec-b154-f18b536eca86\" class=\"RefAuthor\"><span id=\"f8686414-1e1a-47b2-8f0d-f301468a3d71\" class=\"RefSurName\">Landau-west<\/span>\u00a0<span id=\"06867f7e-e8a6-47ed-91d4-8cae78c21599\" class=\"RefGivenName\">D<\/span><\/span>.\u00a0<span id=\"3bec2b6b-5b41-463d-b5fd-324dbf96e954\" class=\"RefArticleTitle\">Solubility of polystyrene in certain vegetable oils, essential oils, and their constituents<\/span>. <span id=\"c949342b-db75-4dbe-adb1-6253993ed93b\" class=\"RefJournalTitle\"><em id=\"99f29f29-493d-437f-9ee9-f004cbdb5ee7\">J Food Science<\/em><\/span>. <span id=\"b9c6ce4e-c82e-4ddf-a893-0aa472d023ac\" class=\"RefYear\">1982<\/span>;<span id=\"e16f2cea-ecdc-4106-9f46-a05b9dac301c\" class=\"RefVolume\">47<\/span>:<span id=\"63a6d6c7-bf41-43e7-9a47-557737da4eb6\" class=\"RefFPage\">1832<\/span>\u2013<span id=\"e092b45b-7ec3-4fbf-9c72-beaa6ff82889\" class=\"RefLPage\">5<\/span>.\u00a0<span id=\"e46d8157-0ca1-4003-8617-ecd32f8aaeba\" class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"67e8ab34-a3ff-454c-a8f2-01153ee524fa\" class=\"RefDOI\">10.1111\/j.1365-2621.1982.tb12893.x<\/span>.<\/p>\r\n<p id=\"R17\" class=\"jrnlRefText\"><span class=\"RefSlNo\">17.<\/span>\u00a0<span id=\"b3cafe43-1d8b-4be4-b896-2fc514be025b\" class=\"RefAuthor\"><span id=\"556dac96-4c82-4067-b921-53d2bf0f9553\" class=\"RefSurName\">Soto<\/span>\u00a0<span id=\"72303865-6b07-405c-a31a-79ba5646bb17\" class=\"RefGivenName\">AM<\/span><\/span>,\u00a0<span id=\"3de299c0-f6c4-485d-b0b0-60212edd6168\" class=\"RefAuthor\"><span id=\"7d3ddf3a-7b96-46a6-a35e-7c274612b6be\" class=\"RefSurName\">Justicia<\/span>\u00a0<span id=\"4a5670c8-d038-45a4-9db7-e2cf44a2489b\" class=\"RefGivenName\">H<\/span><\/span>,\u00a0<span id=\"6b96d62f-1873-476a-8597-fa5113840c05\" class=\"RefAuthor\"><span id=\"e694578e-a740-45f2-a229-8f2ef93b5059\" class=\"RefSurName\">Wray<\/span>\u00a0<span id=\"04262e30-796f-449c-806f-88eb08ef0ffa\" class=\"RefGivenName\">JW<\/span><\/span>,\u00a0<span id=\"3f236610-c1fd-4467-b4c3-77057066f14a\" class=\"RefAuthor\"><span id=\"46635450-7f7f-4647-abb0-688767b851af\" class=\"RefSurName\">Sonnenschein<\/span>\u00a0<span id=\"956d47dc-4aea-4719-959e-7b4a8032f7a7\" class=\"RefGivenName\">C<\/span><\/span>.\u00a0<span id=\"82396179-e068-4d23-8054-b2849978e7c1\" class=\"RefArticleTitle\">\u201cP-Nonyl-phenol: An estrogenic Xenobiotic released from \u201cmodified\u201d Polystyren.\u201d<\/span>.\u00a0<span id=\"d56ef264-378e-403d-9108-4d161d0d8318\" class=\"RefJournalTitle\"><em id=\"e14a06c0-2d82-4e89-9139-d62745116052\">Environ Health Perspect<\/em><\/span>. <span id=\"e0cbefa3-174e-4ee8-9e34-354d99bdb36b\" class=\"RefYear\">1991<\/span>;<span id=\"ac283c35-998e-47db-83a0-4062ea3cb1f0\" class=\"RefVolume\">92<\/span>:<span id=\"462142fb-ed73-4f92-a5a1-813f42644f97\" class=\"RefFPage\">167<\/span>\u2013<span id=\"80123c79-3bc1-47c2-8c3d-ae4ab4942333\" class=\"RefLPage\">73<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"4ee80aed-a344-4b0c-a490-82fed551d631\" class=\"RefDOI\">10.1289\/ehp.9192167<\/span>.<\/p>\r\n<p id=\"R18\" class=\"jrnlRefText\"><span class=\"RefSlNo\">18.<\/span>\u00a0<span id=\"516fe1d2-264a-4068-b649-1ec0d95d7aff\" class=\"RefAuthor\"><span id=\"817fa514-1691-4400-8bb5-45f9cc265724\" class=\"RefSurName\">Ishikawa<\/span>\u00a0<span id=\"478269de-aa2c-4688-8443-85c646ddc5e6\" class=\"RefGivenName\">T<\/span><\/span>,\u00a0<span id=\"811ec1be-29b0-4d45-bfd2-ab47c0c35229\" class=\"RefAuthor\"><span id=\"b9e49b37-d07d-424b-8a70-74037efdaf29\" class=\"RefSurName\">Takano<\/span>\u00a0<span id=\"4adf599f-c64d-4227-bc8e-9c6f1d723fa8\" class=\"RefGivenName\">K<\/span><\/span>,\u00a0<span id=\"364c9c39-828f-462e-8ae9-ad647095f391\" class=\"RefAuthor\"><span id=\"d95269e5-27f1-492d-9f04-c313483f1221\" class=\"RefSurName\">Yasufuku-Takano<\/span>\u00a0<span id=\"aa03eadd-7177-40bd-9416-88099288d3ca\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"15dd28b9-5d3c-4095-bdae-00ceee7a989e\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"25b392a1-8483-42a2-9bfe-ce5c20399c21\" class=\"RefArticleTitle\">Estrogenic impurities in Labware<\/span>. <span id=\"91cc025b-733b-461e-a2c6-c923d3899e9c\" class=\"RefJournalTitle\"><em id=\"d9d5db63-6a67-43b5-b046-7cf849ab2389\">Nat Biotechnol<\/em><\/span>. <span id=\"d12c0715-614b-483d-98e6-01880d2f263b\" class=\"RefYear\">2001<\/span>;<span id=\"9ec7fd31-88b8-4bdf-a46d-47500ed65fcc\" class=\"RefVolume\">19<\/span>:<span id=\"d8568e0f-b58a-4d3f-8e38-9856db29120a\" class=\"RefFPage\">812<\/span>\u2013<span id=\"12facb52-8ac5-442a-a74a-0dbceeac0a3a\" class=\"RefLPage\">812<\/span>. <span class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"66d62ab2-e107-4699-82db-6ca03bc368b3\" class=\"RefDOI\">10.1038\/nbt0901-812<\/span>.<\/p>\r\n<p id=\"R19\" class=\"jrnlRefText\"><span class=\"RefSlNo\">19.<\/span>\u00a0<span id=\"d2d48737-e0f4-4335-ad2c-a3ae1e2bb01b\" class=\"RefAuthor\"><span id=\"4c623559-41b5-499d-b2ab-264e6de02c40\" class=\"RefSurName\">Ramsey<\/span>\u00a0<span id=\"9c6b3a10-528e-4a90-868b-1a62f3972266\" class=\"RefGivenName\">JT<\/span><\/span>,\u00a0<span id=\"69d69dcc-dfaa-497a-b2f3-3119c9643445\" class=\"RefAuthor\"><span id=\"9b5adbfb-dd15-4d26-825e-f543f5d9c574\" class=\"RefSurName\">Diaz<\/span>\u00a0<span id=\"ee55c286-9d8a-4e69-8ab3-dad62381befa\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"48339cb5-2dc3-4acb-8383-182ae86a1d21\" class=\"RefAuthor\"><span id=\"cb35c7a2-6fd5-4198-aeba-c212950b7a1d\" class=\"RefSurName\">Naidu<\/span>\u00a0<span id=\"3266b56a-d564-413f-800b-93a5939e95a8\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"ae49c9cb-342a-489a-aad5-c8ec98c4f64a\" class=\"RefAuthor\"><span id=\"590d7a5c-8fa0-4958-995b-0f49a396aa17\" class=\"RefSurName\">Korach<\/span>\u00a0<span id=\"5b987a03-c81b-4238-bd5c-e9e62c902680\" class=\"RefGivenName\">KS<\/span><\/span>.\u00a0<span id=\"db658a66-06ef-4b35-88da-a6286afce224\" class=\"RefArticleTitle\">Response to Letter to the Editor: \u201cLavender products associated with premature thelarche and prepubertal gynecomastia: Case repors and endocrine disrupting chemicals activities.\u201d<\/span>. <span id=\"d2311124-39a5-4586-b818-cf83ae4bae56\" class=\"RefJournalTitle\"><em id=\"d316bea7-bea5-48b7-b2c5-3d88ff01b54b\">J Clin Endocrinol Metab<\/em><\/span>. <span id=\"9940c86b-00fe-4a3f-a556-ce104d61b70c\" class=\"RefYear\">2020<\/span>;<span id=\"1f8a5b9b-4e06-4b1e-afc7-93e4b330179f\" class=\"RefVolume\">105<\/span>:<span id=\"568e1cd6-4b3d-4001-ab44-d9c44f84baf5\" class=\"RefFPage\">e3500<\/span>\u2013<span id=\"a5df4494-96d2-4b16-b78f-15de10057992\" class=\"RefLPage\">1<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"520c9d15-1cb3-44fe-af89-f04fb59659d6\" class=\"RefDOI\">10.1210\/clinem\/dgaa395<\/span>.<\/p>\r\n<p id=\"R20\" class=\"jrnlRefText\"><span class=\"RefSlNo\">20.<\/span>\u00a0<span id=\"1bf7066b-2952-4a08-99ba-89ec91bc4452\" class=\"RefAuthor\"><span id=\"a808a685-0ee3-43ec-942f-4863d0ff338b\" class=\"RefSurName\">Perry<\/span>\u00a0<span id=\"d8c8272a-c1f0-460f-adad-1e12b6d0d1f2\" class=\"RefGivenName\">NS<\/span><\/span>,\u00a0<span id=\"9c9ff861-2fff-4ee8-b4d0-513067946085\" class=\"RefAuthor\"><span id=\"789d2aa8-b203-4761-a845-ac4e2373e212\" class=\"RefSurName\">Houghton<\/span>\u00a0<span id=\"c0f0b916-c6fb-4f81-ae4b-5940f95ec3bc\" class=\"RefGivenName\">PJ<\/span><\/span>,\u00a0<span id=\"8cd1133e-6643-4be8-8e19-0241c26bd231\" class=\"RefAuthor\"><span id=\"c2ba8e74-62d3-45fd-bd45-c6471ac803fa\" class=\"RefSurName\">Sampson<\/span>\u00a0<span id=\"7bf2ec5f-3636-4c0f-9cdb-aca887441938\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"95d43d75-8254-48b3-aa90-f65c2f34f2c1\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"8ccd7c20-73ff-4dcb-8151-1ed98f9219a4\" class=\"RefArticleTitle\">In-vitro activity of\u00a0<em id=\"1ea652bb-5982-4205-b026-b25cc01446c4\">S. Lavandulaefolia<\/em>\u00a0(Spanish sage) relevant to treatment of Alzheimer\u2019s disease<\/span>.\u00a0<span id=\"030087a7-7ab9-48d4-9501-9e7341bcaeb9\" class=\"RefJournalTitle\"><em id=\"914d9fee-7ee5-4c9e-acfd-95fd47ba7e06\">J Pharm Pharmacol<\/em><\/span>. <span id=\"3c4719df-4ce1-4661-9715-ab1271fa4705\" class=\"RefYear\">2001<\/span>;<span id=\"65a6046d-ea0e-4369-9228-93a549119471\" class=\"RefVolume\">53<\/span>:<span id=\"ee047bdf-97a6-45bb-8f25-ee9f1616e80d\" class=\"RefFPage\">1347<\/span>\u2013<span id=\"3b1c938b-ee3c-4dcc-9c0b-e7642a7cae37\" class=\"RefLPage\">56<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"cc08b3e0-b327-45da-b048-a29bd78b0163\" class=\"RefDOI\">10.1211\/0022357011777846<\/span>.<\/p>\r\n<p id=\"R21\" class=\"jrnlRefText\"><span class=\"RefSlNo\">21.<\/span>\u00a0<span id=\"31a92a93-c67e-418f-848e-beee96705aaf\" class=\"RefAuthor\"><span id=\"2e84b6f0-a78d-4f68-8788-2fe214447dfa\" class=\"RefSurName\">Howes<\/span>\u00a0<span id=\"646bb102-58d5-4ef2-9e49-f764fe04480e\" class=\"RefGivenName\">M-J<\/span><\/span>,\u00a0<span id=\"4cddf6ef-14ca-4ded-8b15-8f09e18f5e29\" class=\"RefAuthor\"><span id=\"5016827f-ff29-4689-a653-537d54213f9e\" class=\"RefSurName\">Houghton<\/span>\u00a0<span id=\"d6aa1457-666c-4858-b6ef-76f247c44acd\" class=\"RefGivenName\">PJ<\/span><\/span>,\u00a0<span id=\"63419e8e-bea1-4957-8bc6-3489d5aff5fc\" class=\"RefAuthor\"><span id=\"2af8ec02-8a8e-4d31-a599-2d1be40c58de\" class=\"RefSurName\">Barlow<\/span>\u00a0<span id=\"809ac861-8ecd-4228-8353-f6d4709c6392\" class=\"RefGivenName\">DJ<\/span><\/span>,\u00a0<span id=\"7e0808b1-06f4-4b4b-8cf1-aaa507c3eaae\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"843f7579-5b9c-4b22-ac43-f59fc5c849a5\" class=\"RefArticleTitle\">Assessment of estrogenic activity in some common essential oil constituents<\/span>. <span id=\"e0b6ffe2-eaf0-47a4-84d0-bfa74b4fc1fb\" class=\"RefJournalTitle\"><em id=\"889b8fe5-a55a-4df5-a364-f6ffea07f45e\">J Pharm and Pharmacol<\/em><\/span>. <span id=\"95e5ebcb-abac-4257-96e6-21df4295481b\" class=\"RefYear\">2002<\/span>;<span id=\"8e931bba-7845-47fc-ab8d-772c501104ee\" class=\"RefVolume\">54<\/span>:<span id=\"e8edf16a-c1d9-4be7-ab27-b382661ece26\" class=\"RefFPage\">1521<\/span>\u2013<span id=\"e02bcafc-0939-4271-87fc-4ea4a602698b\" class=\"RefLPage\">8<\/span>.<\/p>\r\n<p id=\"R22\" class=\"jrnlRefText\"><span id=\"f42a812d-776b-475e-97e0-639fe3067d94\" class=\"RefSlNo\">22.<\/span>\u00a0<span id=\"266ceb2e-d1dd-4f78-98f9-d9cdfe6ed576\" class=\"RefAuthor\"><span id=\"4c9f7eb9-8d9c-4b83-8a74-188f8aef0bba\" class=\"RefSurName\">Nielsen<\/span>\u00a0<span id=\"43384808-ecd6-43bf-bd46-cca263f69553\" class=\"RefGivenName\">JB<\/span><\/span>.\u00a0<span id=\"927fe0d4-51f0-4a46-98f2-97b234b59722\" class=\"RefArticleTitle\">What you see may not always be what you get\u2014Bioavailability and extrapolation from in vitro tests<\/span>.\u00a0<span id=\"0771e873-0277-4d88-8d82-c729ac3cff8b\" class=\"RefJournalTitle\"><em id=\"722ce084-90d8-43d0-8705-5adca3fc1b2b\">Toxicol In Vitro<\/em><\/span>.\u00a0<span id=\"fdcd6f49-48ae-4f7e-8bc4-ff4c503554bd\" class=\"RefYear\">2008<\/span>;<span id=\"1e3a1d8a-db9f-44f1-be11-c539bb0b2a57\" class=\"RefVolume\">22<\/span>:<span id=\"e340f194-147d-441c-a1ee-e995c42dbf41\" class=\"RefFPage\">1038<\/span>\u2013<span id=\"307c0da2-de16-4be8-bfdb-cdf2278bc704\" class=\"RefLPage\">42<\/span>.\u00a0<span id=\"726b4aca-ee8f-43e1-875e-ce1a23398cc9\" class=\"RefComments\">DOI<\/span>: <span id=\"8d586f2a-23b5-4efb-8b48-3a26de56d1ae\" class=\"RefDOI\">10.1016\/j.tiv.2007.12.013<\/span>.<\/p>\r\n<p id=\"R23\" class=\"jrnlRefText\"><span class=\"RefSlNo\">23.<\/span>\u00a0<span id=\"52930ad0-1f3e-42a8-ac23-8464b7024861\" class=\"RefAuthor\"><span id=\"097a2de1-aee8-4e65-b3bc-017e53091f81\" class=\"RefSurName\">Sim\u00f5es<\/span>\u00a0<span id=\"cced6b10-61d2-427b-915d-434fc3efe0c1\" class=\"RefGivenName\">BM<\/span><\/span>,\u00a0<span 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class=\"RefGivenName\">CZ<\/span><\/span>,\u00a0<span id=\"b10a0955-81de-4438-9877-4ca349ccb15e\" class=\"RefAuthor\"><span id=\"2e87fc52-0bb5-46b7-aa40-032b15f6397f\" class=\"RefSurName\">Bittner<\/span>\u00a0<span id=\"ee80b177-c1e9-4d41-b320-226fa015e8a1\" class=\"RefGivenName\">GD<\/span><\/span>,\u00a0<span id=\"fefc2c5a-abc5-457d-9953-aa75d589158a\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"3a3bfa67-b5e6-46a2-b8b8-84d3388c39aa\" class=\"RefArticleTitle\">Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products<\/span>. <span id=\"4144fc82-91fb-4728-9915-a1bd6133db4d\" class=\"RefJournalTitle\"><em id=\"fae77e79-9be3-4953-bb59-30e795d5e3ca\">J Expo Sci Environ Epidemiol<\/em><\/span>. <span id=\"39241d4b-f014-4d7b-a2ec-fa79ee317891\" class=\"RefYear\">2015<\/span>;<span id=\"77090849-c79d-4dac-9c59-b2ef95118cd9\" class=\"RefVolume\">25<\/span>:<span id=\"1a7546e2-39d0-4dcf-945b-b1a2c24dc11d\" class=\"RefFPage\">271<\/span>\u2013<span id=\"51481684-04b1-43ea-9be3-b9bfb3075415\" class=\"RefLPage\">7<\/span>. <span id=\"9e65c8c5-d040-48e4-aaac-df3d31223e0b\" class=\"RefComments\">DOI<\/span>: <span id=\"72f70575-2c5f-4b68-9e62-5f86bb00376e\" class=\"RefDOI\">10.1038\/jes.2014.32<\/span>.<\/p>\r\n<p id=\"R25\" class=\"jrnlRefText\"><span id=\"3c9abeba-f45b-4729-a839-93e5f48b1b26\" class=\"RefSlNo\">25.<\/span>\u00a0<span id=\"0262df48-133d-4fc2-97a0-f648463ae131\" class=\"RefAuthor\"><span id=\"1744c622-4cf9-4357-9288-e4427369f1dd\" class=\"RefSurName\">Sharma<\/span>\u00a0<span id=\"0917b64a-bd8e-423b-8595-340018687914\" class=\"RefGivenName\">K<\/span><\/span>,\u00a0<span id=\"7668c1d4-cdb3-46cb-9c38-1a3d04428ec3\" class=\"RefAuthor\"><span id=\"1d90152b-3e28-43e8-9ecc-ea8095805452\" class=\"RefSurName\">Lanzilotto<\/span>\u00a0<span id=\"d711bc92-afe6-4d6d-90fd-a2adabaeb6ec\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"fd99efce-eb74-4498-a2e3-b750d97a82f6\" class=\"RefAuthor\"><span id=\"0ab9fa07-036d-4164-b6bc-601dc306c2e0\" class=\"RefSurName\">Pandey<\/span>\u00a0<span id=\"a413306d-fb21-4288-980c-7156a48e70d8\" class=\"RefGivenName\">AV<\/span><\/span>.\u00a0<span id=\"bdee1690-f081-4179-9930-c29b6c70ada7\" class=\"RefArticleTitle\">Essential oil metabolites can regulate adrenal androgen production by inhibition of Cyp17A1 activities<\/span>. <span id=\"97328620-7ffa-4cb9-8cef-863e15d14f49\" class=\"RefJournalTitle\"><em id=\"5f55143d-81b2-44dd-94bc-6485d85c01d5\">The FASEB Journal<\/em><\/span>. <span id=\"341323ff-c94a-4797-8506-6370c872c24e\" class=\"RefYear\">2022<\/span>;<span id=\"e7ad1422-9629-4d39-91e8-18c6c6649a26\" class=\"RefVolume\">36<\/span>. <span id=\"46d4e7c8-d87c-4ade-a6eb-b3c957427ceb\" class=\"RefComments\">DOI<\/span>: <span id=\"3c9a950c-ecc4-4d7d-b248-9022968b41d6\" class=\"RefDOI\">10.1096\/fasebj.2022.36.S1.R5889<\/span>.<\/p>\r\n<p id=\"R26\" class=\"jrnlRefText\"><span class=\"RefSlNo\">26.<\/span>\u00a0<span id=\"bf6bf971-fbf9-4fac-8223-cbccfb8efdc7\" class=\"RefAuthor\"><span id=\"16f04a32-516d-4e7d-ac02-18eca3797212\" class=\"RefSurName\">Fouyet<\/span>\u00a0<span id=\"3e5ba62b-90c6-423e-bc3f-316d5fa43275\" class=\"RefGivenName\">S<\/span><\/span>,\u00a0<span id=\"075ace13-3d53-4536-baff-b94d4898664e\" class=\"RefAuthor\"><span id=\"1f25ab5b-28c1-4a2a-8e6a-72886a824959\" class=\"RefSurName\">Olivier<\/span>\u00a0<span id=\"afe4b901-a323-4ea5-8019-7fa6d6ece64c\" class=\"RefGivenName\">E<\/span><\/span>,\u00a0<span id=\"de453e80-ee68-4319-94d8-4c8018a20801\" class=\"RefAuthor\"><span id=\"fc01bfee-a6e7-4530-b673-f082c5c5e2de\" class=\"RefSurName\">Leproux<\/span>\u00a0<span id=\"00caa099-62fe-4910-8dfc-254dc7390aa0\" class=\"RefGivenName\">P<\/span><\/span>,\u00a0<span id=\"4559141d-f4c3-49e0-b1b4-bd25012b0973\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"2fc44f0d-fc7c-491b-8203-181088fff906\" class=\"RefArticleTitle\">Evaluation of placental toxicity of five essential oils and their potential endocrine-disrupting effects<\/span>. <span id=\"003ed9fc-f40f-41fb-9c02-574550f3294a\" class=\"RefJournalTitle\"><em id=\"26db580e-2ab3-4f8a-b212-a5a10cf9831b\">Curr Issues Mol Biol<\/em><\/span>. <span id=\"80712836-1884-4c03-b7ce-2802582baac2\" class=\"RefYear\">2022<\/span>;<span id=\"e5a30580-4a8d-4ab6-9063-24e3148347ac\" class=\"RefVolume\">44<\/span>:<span id=\"36713904-d1b2-4658-b4d9-dae7a37e93e6\" class=\"RefFPage\">2794<\/span>\u2013<span id=\"185099a8-df56-49b1-a764-3205511fdde9\" class=\"RefLPage\">810<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"1da721b3-625f-4e78-9ed9-eab7b605d594\" class=\"RefDOI\">10.3390\/cimb44070192<\/span>.<\/p>\r\n<p id=\"R27\" class=\"jrnlRefText\"><span id=\"f905cbc4-acff-44bd-814c-bfee9a571e93\" class=\"RefSlNo\">27.<\/span>\u00a0<span id=\"339158eb-cc7b-40c5-8dca-97dd97ceda9c\" class=\"RefAuthor\"><span id=\"ba8559f9-aa87-41d9-b969-5485b8de3862\" class=\"RefSurName\">Politano<\/span>\u00a0<span id=\"8af794b7-13a9-4135-9171-467f6dc66ebe\" class=\"RefGivenName\">VT<\/span><\/span>,\u00a0<span id=\"8c0c6624-5596-4b52-8642-4eff2f5ffae4\" class=\"RefAuthor\"><span id=\"ea9617db-0ec2-4a35-a11b-0bbc9e06e8c2\" class=\"RefSurName\">McGinty<\/span>\u00a0<span id=\"9a95e7c7-6127-48c5-8989-f35d11ddadd6\" class=\"RefGivenName\">D<\/span><\/span>,\u00a0<span id=\"6da27abf-4df1-488c-80fc-533694428b72\" class=\"RefAuthor\"><span id=\"6e7bc743-5ded-4fd5-b75c-28fe2b7620c8\" class=\"RefSurName\">Lewis<\/span>\u00a0<span id=\"23e76249-a45c-49f0-aa9e-a26c881a4d3f\" class=\"RefGivenName\">EM<\/span><\/span>,\u00a0<span id=\"fbadb20b-44f5-4f33-8a15-6870b4c39715\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"ee3f4e5f-d21e-47ae-804d-29264826a939\" class=\"RefArticleTitle\">Uterotrophic assay of percutaneous lavender oil in immature female rats<\/span>. <span id=\"1a4722af-e5af-41c6-9e2a-abb046073ae7\" class=\"RefJournalTitle\"><em id=\"3bfae977-c7c8-477e-81b0-208b9c621450\">Int J Toxicol<\/em><\/span>. <span id=\"6465426c-770c-4342-85b9-e122f233ecf5\" class=\"RefYear\">2013<\/span>;<span id=\"8533280a-fe43-496c-9766-50a04c27e27e\" class=\"RefVolume\">32<\/span>:<span id=\"3c98e819-89b7-417e-ae52-9decb48151a9\" class=\"RefFPage\">123<\/span>\u2013<span id=\"46377fa6-9596-4e63-accf-11b9a13bb880\" class=\"RefLPage\">9<\/span>. <span id=\"32ff95d9-3836-445e-9d16-c20f34410dd9\" class=\"RefComments\">DOI<\/span>: <span id=\"bf234d40-9b07-4c13-b805-c8c06b1cdba0\" class=\"RefDOI\">10.1177\/1091581812472209<\/span>.<\/p>\r\n<p id=\"R28\" class=\"jrnlRefText\"><span id=\"7e04c1eb-76be-4040-b757-afd00a34587e\" class=\"RefSlNo\">28.<\/span>\u00a0<span id=\"5bc44a07-03e9-43fb-b20d-dc8abb9b0577\" class=\"RefAuthor\"><span id=\"083bd0ea-e643-44f5-b599-e8568dcf1a4c\" class=\"RefSurName\">Kim<\/span>\u00a0<span id=\"a6b12f33-0244-4bb6-b4c0-69c45286b9ab\" class=\"RefGivenName\">Y-M<\/span><\/span>,\u00a0<span id=\"a5b50b56-6ed3-44db-bc5b-3e7caf44853c\" class=\"RefAuthor\"><span id=\"eee52184-c623-41f9-9c74-fb39f22e998b\" class=\"RefSurName\">Lim<\/span>\u00a0<span id=\"e37dd768-e2d0-40cb-a050-952070795711\" class=\"RefGivenName\">HH<\/span><\/span>.\u00a0<span id=\"15e9d321-d543-46b5-a817-2146a167867b\" class=\"RefArticleTitle\">Association of early pubertal onset in female rats with inhalation of lavender oil<\/span>.\u00a0<span id=\"c9857d49-3a32-4846-83ff-a127824c7c71\" class=\"RefJournalTitle\"><em id=\"3a5f0195-2d38-4db1-a808-93f72d8f5291\">J Korean Med Sci<\/em><\/span>.\u00a0<span id=\"700281fc-a8b3-4e95-b743-217e4a8e23be\" class=\"RefYear\">2022<\/span>;<span id=\"e6799546-8587-4969-9b38-4c883f894464\" class=\"RefVolume\">37<\/span>.\u00a0<span id=\"e333c8b0-ad33-4c2e-b48f-ffe5646534d9\" class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"723f02dc-03de-41dc-9286-77f5da4ddcb1\" class=\"RefDOI\">10.3346\/jkms.2022.37.e9<\/span>.<\/p>\r\n<p id=\"R29\" class=\"jrnlRefText\"><span class=\"RefSlNo\">29.<\/span>\u00a0<span id=\"82b89460-c12c-4039-bf15-31b4936f0ace\" class=\"RefAuthor\"><span id=\"a14dde43-d317-453d-981d-2e29cc2a55ac\" class=\"RefSurName\">Slighoua<\/span>\u00a0<span id=\"40e2d948-c170-45f8-90a8-e2366033dff0\" class=\"RefGivenName\">M<\/span><\/span>,\u00a0<span id=\"7895129c-6e35-443f-a2d5-3d02bb28d13d\" class=\"RefAuthor\"><span id=\"a902cac3-2635-4351-b234-5f0f47f51d9c\" class=\"RefSurName\">Mahdi<\/span>\u00a0<span id=\"10c9f319-ff75-4f6b-81e1-59b67946cadc\" class=\"RefGivenName\">I<\/span><\/span>,\u00a0<span id=\"4f950579-77f2-4aab-9bec-378af5d11a6d\" class=\"RefAuthor\"><span id=\"7c966160-8e5a-4823-9c66-f4cc02b6c034\" class=\"RefSurName\">ez-zahra Amrati<\/span>\u00a0<span id=\"6d275f4f-8c5b-4314-b8ba-4489aa293383\" class=\"RefGivenName\">F<\/span><\/span>,\u00a0<span id=\"0fed714c-6f98-47cd-9738-732042927808\" class=\"RefEtal\">et al<\/span>. <span id=\"1e4785f4-3dc3-478d-8e31-d71bad7a7816\" class=\"RefArticleTitle\">Pharmacological effects of\u00a0<em id=\"0dc0b292-f156-4c3c-bb00-423b1fefd8ff\">Lavandula officinalis<\/em>\u00a0Chaix and its polyphenols: Focus on their in vivo estrogenic and anti-inflammatory properties<\/span>. <span id=\"f5b6b0a4-c767-407e-a4ce-873f5791b7b7\" class=\"RefJournalTitle\"><em id=\"4a5b588c-e0c3-4b5c-9401-d49b4116ffa5\">South African Journal of Botany<\/em><\/span>.\u00a0<span id=\"b693eb88-3f6e-434b-87da-16d71c5984ee\" class=\"RefYear\">2022<\/span>;<span id=\"856f0599-d8bb-400c-9efd-d163ad57c2ed\" class=\"RefVolume\">146<\/span>:<span id=\"c18532b7-5217-4b43-aeac-ecfe2f8d0f60\" class=\"RefFPage\">354<\/span>\u2013<span id=\"af70bcdd-4db4-489a-85e3-9979b427c183\" class=\"RefLPage\">64<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"525ba35b-fc8e-483f-9d51-c0aed41a00d3\" class=\"RefDOI\">10.1016\/j.sajb.2021.11.014<\/span>.<\/p>\r\n<p id=\"R30\" class=\"jrnlRefText\"><span class=\"RefSlNo\">30.<\/span>\u00a0<span id=\"b4beb6c6-4449-4618-a6a6-0166493a8226\" class=\"RefAuthor\"><span id=\"0025eb1a-e259-4b33-b36f-42a8dd095110\" class=\"RefSurName\">Cohn<\/span>\u00a0<span id=\"1de357fe-4467-4975-81b2-7276acc93a0d\" class=\"RefGivenName\">RD<\/span><\/span>,\u00a0<span id=\"67c7db29-271f-44bd-bf44-f8c87c289327\" class=\"RefAuthor\"><span id=\"adaef6ac-b4fc-467e-b837-4e4a2aeb705e\" class=\"RefSurName\">Bornhauser<\/span>\u00a0<span id=\"cbdf6e76-271b-4b40-a3db-db71f6b31516\" class=\"RefGivenName\">C<\/span><\/span>,\u00a0<span id=\"73baaf56-b157-4174-8710-9660e5030a27\" class=\"RefAuthor\"><span id=\"7a7b8d0a-dea5-42de-964b-e47d14a639a0\" class=\"RefSurName\">MacManus<\/span>\u00a0<span id=\"58cd6262-6b2b-40cf-9e29-27c64e991ea2\" class=\"RefGivenName\">D<\/span><\/span>,\u00a0<span id=\"7dccb861-4979-4926-8cec-76adb983fdc1\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"8fc31334-758c-44bf-b5f4-93141132eeb9\" class=\"RefArticleTitle\">A study of lavender and tea tree oils on postmenopausal FSH levels and hot flash severity<\/span>.\u00a0<span id=\"88676e22-2905-420c-be9e-136f1eb24e10\" class=\"RefJournalTitle\"><em id=\"ad9e741f-29e3-47c0-a6b7-ae2771aa858c\">JCO<\/em><\/span>.\u00a0<span id=\"5de4bd12-7180-438f-8013-6ab73204573c\" class=\"RefYear\">2009<\/span>;<span id=\"7b1a5fa6-df47-46a3-9a94-eeecf5a5a104\" class=\"RefVolume\">27<\/span>:<span id=\"b789c39b-c7c4-499b-b935-8e03b655d885\" class=\"RefFPage\">1516<\/span>\u2013<span id=\"31261ae8-dad6-4458-9c7f-242b3d162e04\" class=\"RefLPage\">1516<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>: <span id=\"5146fa68-80f7-4058-82f1-0feb9c11521e\" class=\"RefDOI\">10.1200\/jco.2009.27.15_suppl.1516<\/span>.<\/p>\r\n<p id=\"R31\" class=\"jrnlRefText\"><span class=\"RefSlNo\">31.<\/span>\u00a0<span id=\"b2d8ca3c-50ad-414e-a6e5-edfd65603d69\" class=\"RefAuthor\"><span id=\"65a1d81e-6af2-4663-ae91-d08b0565a0cd\" class=\"RefSurName\">Heger-Mahn<\/span>\u00a0<span id=\"77e95b78-0e12-46d0-95e7-d288e670770f\" class=\"RefGivenName\">D<\/span><\/span>,\u00a0<span id=\"a2422dd8-e9e1-4fe3-983b-0929759f46d4\" class=\"RefAuthor\"><span id=\"97c0a8d1-ff76-4847-be99-8c963b385297\" class=\"RefSurName\">Pabst<\/span>\u00a0<span id=\"f0c73d42-2916-4e02-9f38-b54d376d1e5f\" class=\"RefGivenName\">G<\/span><\/span>,\u00a0<span id=\"1432be98-6dd3-42f7-bb4a-1f041ce43630\" class=\"RefAuthor\"><span id=\"85a08ff9-60f6-475a-95b3-d7b10ffe0e30\" class=\"RefSurName\">Dienel<\/span>\u00a0<span id=\"6c0c9879-f204-4162-8c2b-a8a98928c740\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"d45c3ade-a970-4468-aeaa-bcff0b1034ec\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"a01fdc98-d272-4d74-89fc-a2115283ba65\" class=\"RefArticleTitle\">No interacting influence of lavender oil preparation Silexan on oral contraception using an ethinyl estradiol\/levonorgestrel combination<\/span>. <span id=\"1dfcddd4-517e-4a1e-8d35-87959777e4dd\" class=\"RefJournalTitle\"><em id=\"52141b3d-99b7-4548-a6f8-ee6684cec0a3\">Drugs R D<\/em><\/span>. <span id=\"4de7d65b-061e-4883-a737-be2ee902f8fc\" class=\"RefYear\">2014<\/span>;<span id=\"553e8b71-0b54-48e5-966d-657b8121f4ef\" class=\"RefVolume\">14<\/span>:<span id=\"d9d37bf4-c52f-4dfd-a5b2-9c7dd91c250a\" class=\"RefFPage\">265<\/span>\u2013<span id=\"37d393a1-2b4f-4a16-91bf-d770bf92b0fb\" class=\"RefLPage\">72<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"7616a360-ce44-4b43-967c-7a75cb0923c3\" class=\"RefDOI\">10.1007\/s40268-014-0065-5<\/span>.<\/p>\r\n<p id=\"R32\" class=\"jrnlRefText\"><span class=\"RefSlNo\">32.<\/span>\u00a0<span id=\"25d4e910-2a45-46bd-8e22-40dae1a1dc24\" class=\"RefAuthor\"><span id=\"5f516a7d-9aca-4a99-9a93-e1982c7e381b\" class=\"RefSurName\">Shinohara<\/span>\u00a0<span id=\"36471c20-87b2-4ccb-a323-31ba67cb340a\" class=\"RefGivenName\">K<\/span><\/span>,\u00a0<span id=\"3102076c-1f3c-48b1-a706-1f9fd9dbf30a\" class=\"RefAuthor\"><span id=\"be516982-e440-4eab-a9f7-ee4bb9acf709\" class=\"RefSurName\">Doi<\/span>\u00a0<span id=\"a0ab03c4-c49f-4368-89f2-166a43916cca\" class=\"RefGivenName\">H<\/span><\/span>,\u00a0<span id=\"237015e1-c100-440b-8f0a-083c3884a93a\" class=\"RefAuthor\"><span id=\"d574e352-f4bb-4fdc-a1a8-663e67fa6109\" class=\"RefSurName\">Kumagai<\/span>\u00a0<span id=\"631f1516-65eb-4ebe-ba0c-16df0cb4dc2f\" class=\"RefGivenName\">C<\/span><\/span>,\u00a0<span id=\"87a28617-1d83-4119-a82d-490847c4732c\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"e6e8405d-3324-46a9-8896-7a3f553efd32\" class=\"RefArticleTitle\">Effects of essential oil exposure on salivary estrogen concentration in perimenopausal women<\/span>. <span id=\"73250f7e-882f-481f-9318-3c34244f5a67\" class=\"RefJournalTitle\"><em id=\"9273e5e6-6473-47d4-adf8-a76bd1b8784f\">Neuro Endocrinol Lett<\/em><\/span>. <span id=\"2ce70381-ba95-4be2-b78f-e2a471377dac\" class=\"RefYear\">2016<\/span>;<span id=\"d5dde4ca-9263-41d8-aa11-37b785d60b5f\" class=\"RefVolume\">37<\/span>:<span id=\"96e1dc5c-f98d-4c0d-9ca4-a44f2303eb1e\" class=\"RefFPage\">567<\/span>\u2013<span id=\"a680a63f-411f-49e9-9dae-bf7220b37f04\" class=\"RefLPage\">72<\/span>.<\/p>\r\n<p id=\"R33\" class=\"jrnlRefText\"><span id=\"fe252a8d-2386-4995-9e37-da45264b234e\" class=\"RefSlNo\">33.<\/span>\u00a0<span id=\"90f00960-7213-4f3b-b3a5-22458a21f041\" class=\"RefAuthor\"><span id=\"5f344769-556f-425b-857e-3b3b5c22e1cc\" class=\"RefSurName\">Tirabassi<\/span>\u00a0<span id=\"15e335e4-9493-41c3-94ac-a94bcd9f6986\" class=\"RefGivenName\">G<\/span><\/span>,\u00a0<span id=\"d88419fa-269b-4cb6-bbbe-1b102a2eb96b\" class=\"RefAuthor\"><span id=\"a0257900-6b8a-4c86-bc0c-332a9be4a7c4\" class=\"RefSurName\">Giovannini<\/span>\u00a0<span id=\"f8f53741-d2c9-41a3-b017-b71205be9074\" class=\"RefGivenName\">L<\/span><\/span>,\u00a0<span id=\"4205df16-eff9-4d56-aef1-06a33782ab83\" class=\"RefAuthor\"><span id=\"564083e0-10b1-4be5-b57e-d902456674fc\" class=\"RefSurName\">Paggi<\/span>\u00a0<span id=\"81ab2728-0adf-4121-8165-b927ae9852fb\" class=\"RefGivenName\">F<\/span><\/span>,\u00a0<span id=\"fdaa7f1c-27f1-4dfe-8104-09aacb687fbb\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"30cd6a85-94a7-4cbb-8992-b833d563fc32\" class=\"RefArticleTitle\">Possible efficacy of lavender and tea tree oils in the treatment of young women affected by mild idiopathic Hirsutism<\/span>.\u00a0<span id=\"a832ef95-7b48-46ad-9abc-e7e88841c625\" class=\"RefJournalTitle\"><em id=\"0880b76b-94bf-448b-9fae-9abcc55e6d91\">J Endocrinol Invest<\/em><\/span>. <span id=\"6993174c-3194-4048-89f2-8e7a9952e4ec\" class=\"RefYear\">2013<\/span>;<span id=\"ed095d4c-fde1-4b92-91ae-f818f31dea58\" class=\"RefVolume\">36<\/span>:<span id=\"381ceb2b-1204-4ae1-bed2-b55fffcf3d56\" class=\"RefFPage\">50<\/span>\u2013<span id=\"599f91be-5ad9-4a74-8cba-0967959f4a3e\" class=\"RefLPage\">4<\/span>.\u00a0<span id=\"1f419d6c-df73-4fbd-9274-f5b93948ceef\" class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"ee407aaa-c824-47c4-b275-32bdc992f93a\" class=\"RefDOI\">10.3275\/8766<\/span>.<\/p>\r\n<p id=\"R34\" class=\"jrnlRefText\"><span class=\"RefSlNo\">34.<\/span>\u00a0<span id=\"3dd3f362-afd7-4fd1-8e7d-e9718633a316\" class=\"RefAuthor\"><span id=\"5049bad7-07e5-4a4b-aed2-20cc1893e16c\" class=\"RefSurName\">Lopez-Rodriguez<\/span>\u00a0<span id=\"7e944b1c-e2cd-4449-83e4-813bba229413\" class=\"RefGivenName\">JA<\/span><\/span>,\u00a0<span id=\"29d12021-8715-4bf1-9456-6e9fbb16ddfc\" class=\"RefAuthor\"><span id=\"09f46ac2-3828-4427-8eee-8b337424fb7f\" class=\"RefSurName\">Duelo Marcos<\/span>\u00a0<span id=\"70159730-523d-4a05-bc0f-f124862d9529\" class=\"RefGivenName\">M<\/span><\/span>.\u00a0<span id=\"ba15d1cc-c7b8-4db4-8b05-2abb98480d38\" class=\"RefArticleTitle\">Ginecomastia unilateral en Prepuber Por Aceite de Arbol del te. [unilateral Gynecomastia in young male due to tea tree oil]<\/span>. <span id=\"ff2cce09-940e-4f6b-892e-a07166f024da\" class=\"RefJournalTitle\"><em id=\"725b9012-72cb-46af-aff9-70b4c0f56dc8\">Anales de Pediatr\u00eda<\/em><\/span>. <span id=\"6ac0dc11-6c9e-4970-be93-6dac11ad59e6\" class=\"RefYear\">2014<\/span>;<span id=\"f87fac48-9b26-4e1b-93cd-1187a3ee1ad7\" class=\"RefVolume\">81<\/span>:<span id=\"7b1ec502-e6ca-41c1-ba9e-3dd0009583bc\" class=\"RefFPage\">e18<\/span>\u2013<span id=\"d2b680fb-fe70-4b6a-8fc5-51353ca95bc2\" class=\"RefLPage\">9<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"2718dbfa-9d6e-41ff-8fc1-54bd670f6641\" class=\"RefDOI\">10.1016\/j.anpedi.2014.01.009<\/span>.<\/p>\r\n<p id=\"R35\" class=\"jrnlRefText\"><span class=\"RefSlNo\">35.<\/span>\u00a0<span id=\"953a38e9-2c65-4978-a608-baa0b017112b\" class=\"RefAuthor\"><span id=\"28ed4935-a55f-4574-8372-f27544571fac\" class=\"RefSurName\">Diaz<\/span>\u00a0<span id=\"db544111-b3a6-411b-8c15-33d9cb31e368\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"912d15dd-b820-4e27-a481-01eaa092cc2b\" class=\"RefAuthor\"><span id=\"e7d08c45-7ca3-4720-a980-f967afecc1c6\" class=\"RefSurName\">Luque<\/span>\u00a0<span id=\"f474b119-b5e4-419a-9bc1-113446371f1a\" class=\"RefGivenName\">L<\/span><\/span>,\u00a0<span id=\"ecb1cc05-e39d-4d3d-a69c-5555071242ab\" class=\"RefAuthor\"><span id=\"84f487d5-6e49-4f0c-a354-4c36d96d38de\" class=\"RefSurName\">Badar<\/span>\u00a0<span id=\"df834823-e7a7-44dc-acf3-4d9970d49f3b\" class=\"RefGivenName\">Z<\/span><\/span>,\u00a0<span id=\"70c6adaf-edde-418a-b1d8-9ef5a9f67e05\" class=\"RefEtal\">et al<\/span>.\u00a0<span id=\"9b5c9563-047b-4f4f-ba72-0681032d16e2\" class=\"RefArticleTitle\">Prepubertal gynecomastia and chronic lavender exposure: Report of three cases<\/span>. <span id=\"008fb9de-c7a6-43e0-943c-46a2768652b8\" class=\"RefJournalTitle\"><em id=\"dac39bd1-fcfe-43c6-ab8b-0c411d9f13d3\">J Pediatr Endocrinol Metab<\/em><\/span>. <span id=\"359baeb1-d0d2-4177-b6b5-2bf7ffacbbea\" class=\"RefYear\">2016<\/span>;<span id=\"7ebf3d04-4464-4c62-b3b1-667ac01f7f07\" class=\"RefVolume\">29<\/span>:<span id=\"f8f64376-d0af-4e36-b4d7-718e96a50786\" class=\"RefFPage\">103<\/span>\u2013<span id=\"53c68e5d-082b-4700-b6a6-8718d53e436d\" class=\"RefLPage\">7<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"fd6d923a-497a-44d9-82df-3dfbe91e103d\" class=\"RefDOI\">10.1515\/jpem-2015-0248<\/span>.<\/p>\r\n<p id=\"R36\" class=\"jrnlRefText\"><span class=\"RefSlNo\">36.<\/span>\u00a0<span id=\"c5bac778-99f8-43d5-b7b5-f6f53ebecf8d\" class=\"RefAuthor\"><span id=\"47b3886b-8081-4bc2-b690-435d84d1ee57\" class=\"RefSurName\">Linklater<\/span>\u00a0<span id=\"abe5a84d-6c3d-481a-922e-acbcf158b07b\" class=\"RefGivenName\">A<\/span><\/span>,\u00a0<span id=\"07458f21-0fa6-48f4-835c-f6efb67cf7be\" class=\"RefAuthor\"><span id=\"4172c3ee-dd17-46e5-98c6-8784176d68db\" class=\"RefSurName\">Hewitt<\/span>\u00a0<span id=\"ebad7d1b-ef3c-4eb7-a72e-68f360378a74\" class=\"RefGivenName\">JK<\/span><\/span>.\u00a0<span id=\"fa5765cb-2284-48d0-aabc-de17d677e584\" class=\"RefArticleTitle\">Premature thelarche in the setting of high lavender oil exposure<\/span>. <span id=\"1793f3e8-0803-4186-af96-32e7ecf20602\" class=\"RefJournalTitle\"><em id=\"0d10b5ae-d46b-4e5f-a199-c9b0c420a37e\">J Paediatr Child Health<\/em><\/span>. <span id=\"c225cf33-3362-48bf-b006-42926ffabbfb\" class=\"RefYear\">2015<\/span>;<span id=\"618d1943-5004-4ee4-b513-eae728fdeb0b\" class=\"RefVolume\">51<\/span>:<span id=\"e50a4f97-1ab4-4ff2-a9a0-a8efc88dfe84\" class=\"RefELocation\">235<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"7077b34c-9274-45e0-bc82-fcbd37db521b\" class=\"RefDOI\">10.1111\/jpc.12837<\/span>.<\/p>\r\n<p id=\"R37\" class=\"jrnlRefText\"><span class=\"RefSlNo\">37.<\/span>\u00a0<span id=\"8c5f09a8-3e75-4816-b690-fce5a3dd485c\" class=\"RefAuthor\"><span id=\"5b95ff11-5063-4b6c-94d1-f378eeba7b7e\" class=\"RefSurName\">Block<\/span>\u00a0<span id=\"937d57ca-1693-49d2-a0da-0890eff4ae54\" class=\"RefGivenName\">SL<\/span><\/span>.\u00a0<span id=\"69a90a0e-8d46-49f8-a3da-c38e476d81ee\" class=\"RefArticleTitle\">The possible link between gynecomastia, topical lavender, and tea tree oil<\/span>. <span id=\"a50854c4-1897-4b02-b7b0-c7d966915036\" class=\"RefJournalTitle\"><em id=\"eb47206e-60d2-4685-89c5-0347280d7ee6\">Pediatr Ann<\/em><\/span>. <span id=\"244904e8-d6cd-4d2e-9f10-a9fadc46fa47\" class=\"RefYear\">2012<\/span>;<span id=\"9c01320a-5b42-4b8a-93f9-ee2ac49030f9\" class=\"RefVolume\">41<\/span>:<span id=\"20053882-30ff-4773-a0e1-61afea755ae9\" class=\"RefFPage\">56<\/span>\u2013<span id=\"e4381d7e-8b94-41d0-a74f-518c155f2883\" class=\"RefLPage\">8<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"4f90f65e-526c-40ca-9c16-8c3adef9a9f5\" class=\"RefDOI\">10.3928\/00904481-20120110-05<\/span>.<\/p>\r\n<p id=\"R38\" class=\"jrnlRefText\"><span class=\"RefSlNo\">38.<\/span>\u00a0<span id=\"0d0d512d-70a2-4517-b23c-5e7df3c0dbda\" class=\"RefAuthor\"><span id=\"bd2ce5ed-dc7f-4a15-8407-f6dba35a5491\" class=\"RefSurName\">Hawkins<\/span>\u00a0<span id=\"cca3ece7-f565-4b8a-a1b5-ad6620ab54c8\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"8c25d065-e620-4723-8aeb-7bfcfb52571f\" class=\"RefAuthor\"><span id=\"c0196272-a654-48e2-9bf2-9b86f7568339\" class=\"RefSurName\">Hires<\/span>\u00a0<span id=\"8ed645f5-7961-4ef3-99b1-3e2634410ac0\" class=\"RefGivenName\">C<\/span><\/span>,\u00a0<span id=\"c25c59ee-1d18-4e35-9c3e-baebdeb0c2c3\" class=\"RefAuthor\"><span id=\"f3a98a27-5cc8-4032-9cd0-09f6e343127c\" class=\"RefSurName\">Dunne<\/span>\u00a0<span id=\"c351a6d7-7cbd-45e8-881f-a6c7bc96f080\" class=\"RefGivenName\">E<\/span><\/span>,\u00a0<span id=\"0c368b24-b8ad-4d4c-a47b-d6f9c32ce531\" class=\"RefAuthor\"><span id=\"ad2196db-8f55-45a9-9e80-c1efdd7861b4\" class=\"RefSurName\">Baker<\/span>\u00a0<span id=\"03c1f036-ecc6-46c2-bc5b-832b742ae6ad\" class=\"RefGivenName\">C<\/span><\/span>.\u00a0<span id=\"6bef0464-55c2-47bb-8dd2-f29b912bcdb1\" class=\"RefArticleTitle\">The relationship between lavender and tea tree essential oils and pediatric endocrine disorders: A systematic review of the literature<\/span>. <span id=\"10dfcb6b-9b12-41fe-bb6a-a011ace027b3\" class=\"RefJournalTitle\"><em id=\"9fcce75b-06fc-4659-ae82-dcff9e45ff4d\">Complement Ther Med<\/em><\/span>. <span id=\"cf7e0c1a-652a-4c14-a1c3-3334d6eb19bb\" class=\"RefYear\">2020<\/span>;<span id=\"cab87734-c2ea-46ff-8569-44f796b340d2\" class=\"RefVolume\">49<\/span>:<span id=\"be46f587-fdb4-4839-9ba1-5bda6cff9d27\" class=\"RefFPage\">102288<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"42ab5b8a-429c-4e2a-8b68-19a8e55c5c87\" class=\"RefDOI\">10.1016\/j.ctim.2019.102288<\/span>.<\/p>\r\n<p id=\"R39\" class=\"jrnlRefText\"><span class=\"RefSlNo\">39.<\/span>\u00a0<span id=\"e741d077-13da-4667-93da-ff65d3818a88\" class=\"RefWebSite\"><a href=\"http:\/\/snowyriverlavender.com.au\/lavender-essential-oil-chemistry-standards\/\">http:\/\/snowyriverlavender.com.au\/lavender-essential-oil-chemistry-standards\/<\/a><\/span><\/p>\r\n<p id=\"R40\" class=\"jrnlRefText\"><span class=\"RefSlNo\">40.<\/span>\u00a0<span id=\"ae9d067b-ed8e-4a95-b5f1-9a643518192d\" class=\"RefAuthor\"><span id=\"5b6e08d7-9452-4317-b452-8b7af13ad0a6\" class=\"RefSurName\">Tisserand<\/span>\u00a0<span id=\"7f6b3ed3-b2b5-4e16-900e-4d44e8ef91ce\" class=\"RefGivenName\">R<\/span><\/span>.\u00a0<span id=\"919a41bd-63fa-4687-afdd-e5e0712eccb3\" class=\"RefArticleTitle\">Neither lavender oil nor tea tree oil can be linked to breast growth in young boys<\/span>.\u00a0<span id=\"0ec38e88-b2cc-4a83-9aee-2e9af97bb441\" class=\"RefYear\">2008<\/span>.\u00a0<span class=\"RefComments\">Available at<\/span>:\u00a0<span id=\"b80227da-925b-4721-9fdf-e293fd59cdd3\" class=\"RefWebSite\"><a href=\"https:\/\/roberttisserand.com\/wp-content\/uploads\/2016\/01\/TeaTreeAndLavenderNotLinkedToGynecomastia.pdf\">https:\/\/roberttisserand.com\/wp-content\/uploads\/2016\/01\/TeaTreeAndLavenderNotLinkedToGynecomastia.pdf<\/a><\/span>.<\/p>\r\n<p id=\"R41\" class=\"jrnlRefText\"><span class=\"RefSlNo\">41.<\/span>\u00a0<span id=\"948b1364-441f-4c3e-aa60-4f0c161c96c9\" class=\"RefAuthor\"><span id=\"d6ba4651-b234-4452-9b4f-146a517dfa17\" class=\"RefSurName\">Kurtz<\/span>\u00a0<span id=\"a9a551f8-5562-4aa0-9f41-c036b55ca053\" class=\"RefGivenName\">JL<\/span><\/span>.\u00a0<span id=\"b43c3bee-5a04-4a39-8953-fe48de3b2342\" class=\"RefArticleTitle\">Prepubertal gynecomastia linked to lavender and tea tree oils, (Letter to the Editor)<\/span>. <span id=\"3db7c0da-38fd-408d-b276-17e10fb0361e\" class=\"RefJournalTitle\"><em id=\"5ecf1c6c-8f06-485c-acdc-c917e2017a11\">N Engl J Med<\/em><\/span>. <span id=\"edb0ebc5-f725-4ba6-b975-50e72c440baa\" class=\"RefYear\">2007<\/span>;<span id=\"95094366-4ca2-4c1c-91f4-441bee39b540\" class=\"RefVolume\">356<\/span>:<span id=\"120c56e8-6418-491c-a611-7ca8eaf69eee\" class=\"RefFPage\">2542<\/span>\u2013<span id=\"850e65f4-9e93-4535-8f9d-5fe8c510d781\" class=\"RefLPage\">3<\/span>.<\/p>\r\n<p id=\"R42\" class=\"jrnlRefText\"><span class=\"RefSlNo\">42.<\/span>\u00a0<span id=\"3f65dddc-12fa-4055-8cd8-374bc43ae7c8\" class=\"RefAuthor\"><span id=\"ffcebd3e-74a7-4b44-a779-d151af06508d\" class=\"RefSurName\">Dean<\/span>\u00a0<span id=\"1775403d-fd1a-442b-babf-d8cf5e38c7c4\" class=\"RefGivenName\">CJ<\/span><\/span>.\u00a0<span id=\"4309d899-31cf-435c-97b3-9b11da744a3b\" class=\"RefArticleTitle\">Prepubertal gynecomastia linked to lavender and tea tree oils. (Letter to the Editor)<\/span>. <span id=\"e79d8281-4eff-4e18-8964-b09bb2a64698\" class=\"RefJournalTitle\"><em id=\"c374a8da-5861-44bf-803d-9a82272ee5ab\">N Engl J Med<\/em><\/span>. <span id=\"0b7c32bd-da4f-4b37-b7f9-497a7d54b459\" class=\"RefYear\">2007<\/span>;<span id=\"1613a2c8-6fd5-4469-b02a-9c15bd6e81d6\" class=\"RefVolume\">356<\/span>:<span id=\"ed67e9fa-4c83-48e3-9026-c93fe3df1533\" class=\"RefFPage\">2543<\/span>.<\/p>\r\n<p id=\"R43\" class=\"jrnlRefText\"><span class=\"RefSlNo\">43.<\/span>\u00a0<span id=\"90a6b04b-5cf7-481d-91a2-f89424fb0d4e\" class=\"RefAuthor\"><span id=\"b9e02978-f3ad-4723-9155-987ea3731b4f\" class=\"RefSurName\">Hawkins<\/span>\u00a0<span id=\"2208acae-14e4-4b0a-bf98-bf0e6469bf91\" class=\"RefGivenName\">J<\/span><\/span>,\u00a0<span id=\"aea2e2d5-aa2b-4898-9e90-b5c1df16744a\" class=\"RefAuthor\"><span id=\"1e91afca-2048-4cde-a5e2-a465790cbfac\" class=\"RefSurName\">Hires<\/span>\u00a0<span id=\"18d15447-62f4-4ab5-b4fe-a524fa54ff2e\" class=\"RefGivenName\">C<\/span><\/span>,\u00a0<span id=\"7d40c1ae-26fb-4105-afaa-a04c25ba3d99\" class=\"RefAuthor\"><span id=\"0f2402ab-0689-4447-ac4c-e7afb090a698\" class=\"RefSurName\">Dunne<\/span>\u00a0<span id=\"17085941-09e2-4e00-a5c9-da8196fa2a5e\" class=\"RefGivenName\">E<\/span><\/span>,\u00a0<span id=\"82d27299-ac9b-493a-878a-41d0bbbf0b15\" class=\"RefAuthor\"><span id=\"c3c2bcdd-adc0-4df8-9b82-143da6765ca0\" class=\"RefSurName\">Keenan<\/span>\u00a0<span id=\"97c326db-6ceb-4bb2-a367-e476932c23e5\" class=\"RefGivenName\">L<\/span><\/span>.\u00a0<span id=\"5b89eb98-7b8d-44a3-9755-b9d4324ff223\" class=\"RefArticleTitle\">Prevalence of endocrine disorders among children exposed to lavender essential oil and tea tree essential oils<\/span>.\u00a0<span id=\"ea6ca47b-1bcd-4417-84ce-4f4f0f6173fe\" class=\"RefJournalTitle\"><em id=\"19c8f8dc-5d55-4b5b-84b6-0e80c9650f32\">Int J Pediatr Adolesc Med<\/em><\/span>. <span id=\"15a5cb53-c9eb-45d9-ac6e-b43ff776c269\" class=\"RefYear\">2022<\/span>;<span id=\"bcfe6744-0042-4a1f-8a1f-4ff4d260a32f\" class=\"RefVolume\">9<\/span>:<span id=\"92aa236e-4dba-4f2e-940e-10d801bfcdd0\" class=\"RefFPage\">117<\/span>\u2013<span id=\"30009401-86f4-4baa-9c86-d2ccb61ba73c\" class=\"RefLPage\">24<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>:\u00a0<span id=\"d87d6dda-4a08-4a23-b2d4-21f4844e7aa3\" class=\"RefDOI\">10.1016\/j.ijpam.2021.10.001<\/span>.<\/p>\r\n<p id=\"R44\" class=\"jrnlRefText\"><span class=\"RefSlNo\">44.<\/span>\u00a0<span id=\"d2b35005-e87f-446c-8034-2d03b6e44f06\" class=\"RefAuthor\"><span id=\"67ff9fdf-66db-4043-b717-af713066f6a1\" class=\"RefSurName\">Bloch<\/span>\u00a0<span id=\"f18956c0-097d-419f-bb32-0ed7a5c9123f\" class=\"RefGivenName\">CA<\/span><\/span>,\u00a0<span id=\"9371d326-88de-42b1-bdbe-e76ddfe0d2b9\" class=\"RefAuthor\"><span id=\"4e9e0a92-0c6d-4807-a334-331be3aa70d3\" class=\"RefSurName\">Korach<\/span>\u00a0<span id=\"f077d98c-3cf3-442c-b2e2-b844d3dae8b9\" class=\"RefGivenName\">KS<\/span><\/span>, , .\u00a0<span id=\"ab63dffd-852d-4885-ac23-34a7a32b0352\" class=\"RefArticleTitle\">Prepubertal gynecomastia linked to lavender and tea tree oils (rebuttal letter)<\/span>. <span id=\"2ba6619d-3c23-449a-b27c-9b0258fb048b\" class=\"RefJournalTitle\"><em id=\"903a265a-1023-4930-81ce-a693ae04d2d8\">N Engl J Med<\/em><\/span>. <span id=\"b2e1a38a-4cc5-442e-bdf1-aa325fb62285\" class=\"RefYear\">2007<\/span>;<span id=\"3ba2db3c-c08d-49b5-b788-ef9bc18281e9\" class=\"RefVolume\">356<\/span>:<span id=\"28d311c8-de23-45c4-9c21-76daba327d37\" class=\"RefFPage\">2543<\/span>\u2013<span id=\"614b9db9-dce5-4040-8dfe-ca1144bc298e\" class=\"RefLPage\">44<\/span>.\u00a0<span class=\"RefComments\">DOI<\/span>: .<\/p>\r\n<p id=\"R45\" class=\"jrnlRefText\"><span class=\"RefSlNo\">45.<\/span>\u00a0<span id=\"18c6d43f-ab6c-462a-982b-57772e022f46\" class=\"RefAuthor\"><span id=\"e867505f-634d-42ec-ab40-b6be11007743\" class=\"RefSurName\">Kurto\u011flu<\/span>\u00a0<span id=\"081d855d-50d8-46d3-b2f9-4a7f8052e208\" class=\"RefGivenName\">S<\/span><\/span>,\u00a0<span id=\"0dfd8864-d8c1-4e59-8b51-c8c365df7ba1\" class=\"RefAuthor\"><span id=\"095c0613-8013-43bc-9f37-c9b36657524f\" class=\"RefSurName\">Armut<\/span>\u00a0<span id=\"b7e4d340-8830-4a30-bc3b-464bb93f3637\" class=\"RefGivenName\">M<\/span><\/span>.\u00a0<span id=\"5fc7ce5b-f6da-4c34-93a4-6e57cdb70f1c\" class=\"RefArticleTitle\">Puberty prococious due to chronic lavender oil application<\/span>. <span id=\"178ce4e8-26b0-4759-b81b-71dd1ff032e3\" class=\"RefJournalTitle\"><em id=\"9d4574d1-7c8e-44a6-b47b-7c246710e29e\">J Pediatr Acad<\/em><\/span>. <span id=\"fd811981-abd3-4b74-a65d-38486c8f504d\" class=\"RefYear\">2020<\/span>;<span id=\"be2bb1c9-0417-446b-a800-13d901d81cf4\" class=\"RefVolume\">1<\/span>:<span id=\"712a0588-ee0b-4d4a-88f1-b8e91401cb20\" class=\"RefFPage\">107<\/span>\u2013<span id=\"ab8a562b-393e-4ad7-8490-80455703c714\" class=\"RefLPage\">8<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"503e8135-dd35-4532-9f82-d3357e24261d\" class=\"RefDOI\">10.38092\/JPA-2020-181739<\/span>.<\/p>\r\n<p id=\"R46\" class=\"jrnlRefText\"><span class=\"RefSlNo\">46.<\/span>\u00a0<span id=\"dd50c11d-c8dc-4139-b953-92443b2ae16e\" class=\"RefAuthor\"><span id=\"6079cd77-6041-48ea-a25f-aa1eb6c9b0a6\" class=\"RefSurName\">Hennekens<\/span>\u00a0<span id=\"75cf3c09-8a00-497a-a00d-95b0c15927dd\" class=\"RefGivenName\">CH<\/span><\/span>,\u00a0<span id=\"d06499c2-d154-4c29-a3bd-a6312e22fe08\" class=\"RefAuthor\"><span id=\"1c44537d-d170-4261-bbe4-96c13bcffcf5\" class=\"RefSurName\">DeMets<\/span>\u00a0<span id=\"90ed48de-f14d-45f0-ae2e-a8ac1d9b8703\" class=\"RefGivenName\">D<\/span><\/span>.\u00a0<span id=\"00faac02-5694-4b7e-bc68-8faa3d6a8fb4\" class=\"RefArticleTitle\">Statistical association and causation. Contributions of different types of evidence. <\/span><span id=\"c9ba60aa-625e-401c-8781-db0a6b3737d3\" class=\"RefJournalTitle\"><em id=\"ff1b848c-8fdb-4535-9174-499a3b65ecb6\">JAMA<\/em><\/span>. <span id=\"ae622b99-d8a9-47a2-b57c-89fb13aa8049\" class=\"RefYear\">2011<\/span>;<span id=\"5a8ecea7-c5e2-4e9d-9aec-3b62a087123c\" class=\"RefVolume\">305<\/span>:<span id=\"d483d3b9-b237-4359-a6b2-bcd0e1debfa6\" class=\"RefFPage\">1134<\/span>\u2013<span id=\"2b1b1866-a8cc-4cb8-b3a4-e524cede11a4\" class=\"RefLPage\">5<\/span>. <span class=\"RefComments\">DOI<\/span>: <span id=\"264275cd-a10f-41b0-b66d-31f638c7ce2c\" class=\"RefDOI\">10.1001\/jama.2011.322<\/span>.<\/p>","wpcf-article_received_date":"20230707","wpcf-article_accepted_date":"20230802","wpcf-article_published_online":"20230831","wpcf-podcast":"","wpcf-ogg":"","wpcf-article_end_page":"","wpcf-article_start_page":"","wpcf-acknowledgements":"","wpcf-errata_pdf":"","wpcf-article_flipper_image":"","wpcf-corrected_online":null,"wpcf-supplementary_information":"","wpcf-article_highlight_pdf":"","data_availability":"Data sharing is not applicable to this article as no datasets were generated or analysed during the current study\/during the writing of this article.","digital_features":""},"_links":{"self":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts\/60927","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/users\/100365"}],"replies":[{"embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/comments?post=60927"}],"version-history":[{"count":14,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts\/60927\/revisions"}],"predecessor-version":[{"id":67502,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/posts\/60927\/revisions\/67502"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/media\/60977"}],"wp:attachment":[{"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/media?parent=60927"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/categories?post=60927"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/touchendocrinology.com\/wp-json\/wp\/v2\/tags?post=60927"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}