Lavender Products Associated With Premature Thelarche and Prepubertal Gynecomastia: Case Reports and Endocrine-Disrupting Chemical Activities

Abstract

Context: Previous case reports associated prepubertal gynecomastia with lavender-containing fragrances, but there appear to be no reports of premature thelarche.

Objective: To add to a case series about lavender-fragranced product use and breast growth in children and to measure endocrine-disrupting chemical activity of essential oil components.

Design, setting, and patients: Patients experiencing premature thelarche or prepubertal gynecomastia with continuous exposure to lavender-fragranced products were evaluated in the pediatric endocrinology departments of two institutions. Mechanistic in vitro experiments using eight components of lavender and other essential oils were performed at National Institute of Environmental Health Sciences.

Main outcome measures: Case reports and in vitro estrogen and androgen receptor gene expression activities in human cell lines with essential oils.

Results: Three prepubertal girls and one boy with clinical evidence of estrogenic action and a history of continuous exposure to lavender-containing fragrances were studied. Breast growth dissipated in all patients with discontinuation of the fragranced products. Some of the components tested elicited estrogenic and antiandrogenic properties of varying degrees.

Conclusion: We report cases of premature thelarche that resolved upon cessation of lavender-containing fragrance exposure commonly used in Hispanic communities. The precise developmental basis for such conditions could be multifactorial. In vitro demonstration of estrogenic and antiandrogenic properties of essential oil components suggests essential oils in these cases could be considered a possible source and supports a possible link with idiopathic prepubertal breast development. Whether the level of lavender oil estrogenic potency is sufficient to cause these effects is unknown.

Figure 1.

ERα ERE-mediated transcriptional activity, coactivator SRC-2 recruitment, binding to the ERα LBD, and ERα-regulated gene expression. (A) Dose-dependent estrogenic responses of HepG2 cells. The cells were transfected with ERE-luciferase and human ERα expression plasmid [plasmid cloning DNA (pcDNA)/ERα]. A Dunnett multiple comparison test was performed in comparison with the vehicle control. All experiments were performed at least three times. Results are a representation of one experiment and are presented as mean ± SEM. (B) SRC-2 transcriptional enhancement of HepG2 cells. The cells were transfected with human pcDNA/ERα plasmids, with or without pcDNA/SRC-2. Data were normalized against each vehicle group. A Tukey multiple comparison test was performed in comparison with ERα and SRC-2 plus ERα treatment groups. All experiments were performed at least three times. Results are an average of the experiments and are presented as mean ± SEM. (C) Binding to the ERα-LBD in HepG2 cells. The cells were cotransfected with pG5-luciferase reporter plasmid and the expression plasmids for the Gal4-DBD-fused SRC-2-NR-box (pM-SRC-2-NR) in the presence of VP16-AD (pACT) or VP16-AD-fused-ERα WT-LBD. Data were normalized against each vehicle group and its respected pACT treatment group. A Dunnett multiple comparison test was performed in comparison with vehicle control ERα-LBD. All experiments were performed at least three times. Results are an average of the experiments and are presented as mean ± SEM. (D) Induction of ERα endogenous genes and inhibition of induction when cotreated with the antagonist ICI in MCF-7 cells. Total RNA was extracted and mRNA levels of GREB1, PGR, and CTSD genes were quantified by quantitative PCR analysis. All gene fold changes were normalized against ACTB. Results are presented as mean ± SEM. “a” Denotes statistical significance in comparison with vehicle control, P < 0.05; and “b” denotes statistical significance in comparison against each treatment group, with or without the addition of ICI, P < 0.05. (A–C) *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Luc, luciferase.

Figure 2.

AR MMTV-mediated transcriptional activity and AR-regulated gene expression. (A) Dose-dependent antiandrogenic responses of MDA-kb2 cells when cotreated with testosterone (T). A Dunnett multiple comparison test was performed in comparison with 1 nM T. All experiments were performed at least three times. Results are a representation of one experiment and are presented as mean ± SEM. (B) Antiandrogenic responses of endogenous genes in MDA-kb2 cells when cotreated with T. Total RNA was extracted and mRNA levels of the genes SEC14L2, CYP4F8, and UGT2B28 were quantified by quantitative PCR analysis. All gene fold changes were normalized against ACTB. A Dunnett multiple comparison test was performed in comparison with 1 nM T. All experiments were performed at least three times. Results are an average of the experiments and are presented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Luc, luciferase.