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Prepubertal Gynecomastia Linked to Lavender and Tea Tree Oils« Back to Volume 23, Issue 2, June 2007 - Table of Contents Prepubertal gynecomastia is rare and should always be considered pathological and worthy of a compete assessment to determine the cause, even though the underlying pathology is not often determined. In the paper by Henley et al, 3 patients were reported in whom the development of gynecomastia was associated with repeated exposure to topical products containing lavender and tea tree oils. Gynecomastia resolved once use of the products ceased. The patients were 4 5/12, 10 1/12, and 7 10/12 years of age and presented gynecomastia of 2-3 weeks, 5 months, and 1 month duration, respectively. They had no exposure to exogenous estrogens (ingestants, salves, or ointments) and did not report using drugs, medications, soy products, herbal supplements, or lotions. Breast sizes were Tanner stage 2, ranging in size from 2.0 to 4.0 cm in diameter and genitalia were prepubertal Tanner stage 1. Laboratory data were unremarkable with normal serum concentrations of sex steroids and other hormones. The mother of one patient reported applying “healing balm” which contained lavender oil daily shortly before breasts were noted. Another patient was applying a styling gel to his hair and scalp every morning and regularly using shampoo, both containing lavandaula angustifolia (lavender) oil and maleleuca alternifolia (tea tree) oil for 9 months. The last patient also used lavender-scented commercial skin lotions and soap intermittently. The gynecomastia was resolved in these 3 patents once these products were discontinued. Furthermore, the authors performed studies in human breast-cancer cell lines MCF-7 and MDA-kb2 to determine the estrogenic and antiandrogenic activities, respectively, of the oils used by the patients to determine if the oils were the culprit in the development of gynecomastia. These cells express estrogen or androgen receptors and were cultured with various concentrations of the lavender and tee tree oil. Luciferase assays, reverse-transciptase, and real time polymerase-chain reactions (PCR) analyses were performed. Both oils stimulated luciferase activity in MCF-1 cells in a dose-dependant manner. The estrogen receptor antagonist, fulvestrant, inhibited the transactivation of the luciferase, indicating that the activity of the oils was estrogen-receptor dependent. Further experiments indicated that the 2 oils modulated the expression of the estrogen regulated endogenous genes in a manner similar to the effect of 1nM 17 beta-estradiol. The potential antiandrogenic properties of lavender and tea tree oil were performed in the MDA-kb2 cells with androgen receptors trans-fected with an androgen-inducible reporter plasmid. Neither lavender or tea tree oil transactivated the luciferase reporter plasmid at any concentration tested; whereas the cells with the androgen-receptor agonist dihydrotestosterone (DHT) expressed an increase in luciferase activity that was almost 4 times greater than the controls. Transactivation of the luciferase reporter plasmid by 0.1 nM DHT was inhibited by both lavender and tea tree oil in a concentration dependent manner and inhibited androgen inducible genes. The antiandrogenic properties of the oils did not cause down regulation of the expression of the androgen receptors. The authors concluded that lavender and tea tree oils contain endocrine-disrupting activity that cause an imbalance in estrogen and androgen pathway signaling resulting in prepubertal gynecomastia. Editor’s CommentMost often the cause of male prepubertal gynecomastia is considered of idiopathic nature, since exposure to environmental agents that disrupt the endocrine system with disproportionate estrogen and androgen pathway signaling is difficult to prove. The authors of the study should be congratulated for pursuing the elucidation of the cause of the prepubertal gynecomastia present in 3 children who were using commercially over-the-counter products containing lavender and tea tree oils. Through sophisticated in vitro studies they demonstrated that these products had estrogenic and antiandrogenic properties equivalent to those of estradiol and DHT in a threshold dose dependent action. These oils are prevalent and readily available in multiple over-the-counter commercial topical products including shampoos, hair gels, soaps, and body lotions. The frequency of the prepubertal gynecomastia caused by these and /or other similar products is not known, nor it is known if girls, adolescents, or female and male adults are also affected by the repeated exposure to estrogenic and antiandrogenic actions of these or other oils contained in multiple products readily available. Will the FDA follow through? A comprehensive clinical assessment provided the clues, these were followed through with the appropriate science, the cycle was completed and new avenues have been opened for future studies in the field. Further discussion with "Letters to the Editor" regarding this article is published in the New England Journal of Medicine.1 Too bad that most physicians in practice often lack the time to elicit the clues that patients bring to the clinic and do not have the motivation and perseverance to follow through with scientific methods to corroborate the observations. If you search you shall find. Fima Lifshitz , MD Reference - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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