On 2015 Sep 18, Alejandro Diaz commented:

Prepubertal gynecomastia is a very rare condition and there have been an unexpected number of cases reported in the Miami area. This case report highlighted three cases. However, we have seen many other children in our practices with prepubertal gynecomastia or thelarche who were similarly exposed to the lavender-containing cologne described in our report. Unfortunately, the evaluation and follow up for these children was not as in-depth as in the cases that we presented in the article, which included chemical analysis of the cologne product.

In Politano VT, 2013 article, uterotrophic assay, performed in immature female rats, was used to evaluate estrogenic activity in vivo. However, these rats were only treated with lavender oil for a period of 3 days, whereas the children we reported on were exposed to the lavender-containing cologne for several years. As described by Henley DV, 2007, the estrogenic activity of lavender is weak, which may explain why there was not uterotrophic effects on these rats.

You mentioned that the reason Henley found that lavender and tea tree oil activated the estrogen receptor was due to the use of polystyrene in their test system as opposed to the use of glass. Both Ohno K, 2003 and Fail PA, 1998 could not demonstrate estrogenic response from polystyrene. Therefore, this explanation is not substantiated. Moreover, there was an estrogenic response to the lavender and tea tree oils, but not to the control substance, despite having used the same test system containers in both conditions.

While it is true that there are additional components in many lavender preparations, we have not found prepubertal gynecomastia to be associated with other non-lavender-containing colognes or topical products. Thus, lavender itself is a logical and well-founded explanation for the physical findings in our patients.

Regarding tea tree oil, I previously evaluated a patient who was exposed over a period of several years to numerous products containing tea tree oil, including shampoos, toothpaste, detergents, home cleaning products, and melaleuca essential oil for minor cuts, burns, and other skin issues. He developed severe prepubertal gynecomastia that improved upon discontinuation of the exposure to these products. As I did in the cases of lavender exposure, I conducted a complete endocrine evaluation and his hormone levels were all within normal ranges. I did not publish this case at the request of his parents, who were in the tea tree oil industry. As clinicians, if we find patients with prepubertal gynecomastia who have been exposed for prolonged periods of time to substances known to activate the estrogen receptor, it provides substantial evidence of causality.

The possibility exists that there are contaminants that have estrogenic activity in these preparations. However, it is the responsibility of the industry that the products as sold are safe for human exposure.

It is, however, of utmost importance to publish these case reports to offer the balance you refer to, and to deepen the scientific knowledge base and protect consumers from unnecessary harm. Clinicians must be informed and use their clinical judgment to determine what is best for their individual patients.

Alejandro Diaz, M.D. and Marco Danon, M.D. Pediatric Endocrinologists

On 2015 Sep 14, Tony Larkman commented:

It is disappointing that the authors didn’t include or at least refer to the following two articles in this paper: 1. Politano VT et al (2013), Uterotrophic Assay of Percutaneous Lavender Oil in Immature Female Rats; International Journal of Toxicology; 32(2): 123-9 (http://www.ncbi.nlm.nih.gov/pubmed/23358464) 2. Carson CF et al. (2014), Lack of evidence that essential oils affect puberty; Reproductive Toxicology; 44:50-1 (http://www.ncbi.nlm.nih.gov/pubmed/24556344)

The first paper largely exonerates lavender oil through the ’gold standard’ uterotrophic assay while the second hypothesizes a mechanism that may be causal in incidences of both gynecomastia and premature thelarche as well as the ‘in vitro’ findings of Henley et al (2007) where they in fact used polystyrene in their test system and not glass. Based on these it is not impossible to conceive that other endocrine disruptors may have been inadvertently present in the material tested.

A further, as yet untested, hypothesis for these manifestations is the high incidence of adulteration in essential oils. The incidence of adulteration in TTO is remarkably high as reported in Wong YF et al. (2014) Enantiomeric distribution of selected terpenes for authenticity assessment of Australian Melaleuca alternifolia oil; Industrial Crops & Products; 67: 475-83 (http://ijt.sagepub.com/content/early/2013/01/24/1091581812472209) where more than 50% of 43 commercial samples tested failed to comply with the proposed chiral ratios. Of 15 commercially sourced samples in the European Union 73% of these showed significant differences in chiral abundances while TTO from both North America and Asia also displayed similar results where ≥50% of the tested samples did not match the expected results. In material of Chinese origin the incidence rises to 100%. An extraordinary range of compounds never found in pure TTO has been coincidentally detected so it has been further hypothesized that this, along with the likelihood that the material used is heavily oxidized, may be significant source of problems such as allergic contact dermatitis attributed to the use of TTO as well as conditions related to endocrine disruption.

It is disappointing for the tea tree oil industry as a whole that TTO continues to be mentioned as a potential endocrine disruptor without a more balanced view being presented when there are clear indications available in the literature that the original proposal by Henley et al in 2007 may be flawed. The fact that TTO was not present at all in any of the material tested is also disappointing as TTO can in no way be implicated yet its mention continues to promulgate the link and implicate TTO unfairly.

On 2015 Sep 14, Tony Larkman commented:

It is disappointing that the authors didn’t include or at least refer to the following two articles in this paper: 1. Politano VT et al (2013), Uterotrophic Assay of Percutaneous Lavender Oil in Immature Female Rats; International Journal of Toxicology; 32(2): 123-9 (http://www.ncbi.nlm.nih.gov/pubmed/23358464) 2. Carson CF et al. (2014), Lack of evidence that essential oils affect puberty; Reproductive Toxicology; 44:50-1 (http://www.ncbi.nlm.nih.gov/pubmed/24556344)

The first paper largely exonerates lavender oil through the ’gold standard’ uterotrophic assay while the second hypothesizes a mechanism that may be causal in incidences of both gynecomastia and premature thelarche as well as the ‘in vitro’ findings of Henley et al (2007) where they in fact used polystyrene in their test system and not glass. Based on these it is not impossible to conceive that other endocrine disruptors may have been inadvertently present in the material tested.

A further, as yet untested, hypothesis for these manifestations is the high incidence of adulteration in essential oils. The incidence of adulteration in TTO is remarkably high as reported in Wong YF et al. (2014) Enantiomeric distribution of selected terpenes for authenticity assessment of Australian Melaleuca alternifolia oil; Industrial Crops & Products; 67: 475-83 (http://ijt.sagepub.com/content/early/2013/01/24/1091581812472209) where more than 50% of 43 commercial samples tested failed to comply with the proposed chiral ratios. Of 15 commercially sourced samples in the European Union 73% of these showed significant differences in chiral abundances while TTO from both North America and Asia also displayed similar results where ≥50% of the tested samples did not match the expected results. In material of Chinese origin the incidence rises to 100%. An extraordinary range of compounds never found in pure TTO has been coincidentally detected so it has been further hypothesized that this, along with the likelihood that the material used is heavily oxidized, may be significant source of problems such as allergic contact dermatitis attributed to the use of TTO as well as conditions related to endocrine disruption.

It is disappointing for the tea tree oil industry as a whole that TTO continues to be mentioned as a potential endocrine disruptor without a more balanced view being presented when there are clear indications available in the literature that the original proposal by Henley et al in 2007 may be flawed. The fact that TTO was not present at all in any of the material tested is also disappointing as TTO can in no way be implicated yet its mention continues to promulgate the link and implicate TTO unfairly.

On 2015 Sep 18, Alejandro Diaz commented:

Prepubertal gynecomastia is a very rare condition and there have been an unexpected number of cases reported in the Miami area. This case report highlighted three cases. However, we have seen many other children in our practices with prepubertal gynecomastia or thelarche who were similarly exposed to the lavender-containing cologne described in our report. Unfortunately, the evaluation and follow up for these children was not as in-depth as in the cases that we presented in the article, which included chemical analysis of the cologne product.

In Politano VT, 2013 article, uterotrophic assay, performed in immature female rats, was used to evaluate estrogenic activity in vivo. However, these rats were only treated with lavender oil for a period of 3 days, whereas the children we reported on were exposed to the lavender-containing cologne for several years. As described by Henley DV, 2007, the estrogenic activity of lavender is weak, which may explain why there was not uterotrophic effects on these rats.

You mentioned that the reason Henley found that lavender and tea tree oil activated the estrogen receptor was due to the use of polystyrene in their test system as opposed to the use of glass. Both Ohno K, 2003 and Fail PA, 1998 could not demonstrate estrogenic response from polystyrene. Therefore, this explanation is not substantiated. Moreover, there was an estrogenic response to the lavender and tea tree oils, but not to the control substance, despite having used the same test system containers in both conditions.

While it is true that there are additional components in many lavender preparations, we have not found prepubertal gynecomastia to be associated with other non-lavender-containing colognes or topical products. Thus, lavender itself is a logical and well-founded explanation for the physical findings in our patients.

Regarding tea tree oil, I previously evaluated a patient who was exposed over a period of several years to numerous products containing tea tree oil, including shampoos, toothpaste, detergents, home cleaning products, and melaleuca essential oil for minor cuts, burns, and other skin issues. He developed severe prepubertal gynecomastia that improved upon discontinuation of the exposure to these products. As I did in the cases of lavender exposure, I conducted a complete endocrine evaluation and his hormone levels were all within normal ranges. I did not publish this case at the request of his parents, who were in the tea tree oil industry. As clinicians, if we find patients with prepubertal gynecomastia who have been exposed for prolonged periods of time to substances known to activate the estrogen receptor, it provides substantial evidence of causality.

The possibility exists that there are contaminants that have estrogenic activity in these preparations. However, it is the responsibility of the industry that the products as sold are safe for human exposure.

It is, however, of utmost importance to publish these case reports to offer the balance you refer to, and to deepen the scientific knowledge base and protect consumers from unnecessary harm. Clinicians must be informed and use their clinical judgment to determine what is best for their individual patients.

Alejandro Diaz, M.D. and Marco Danon, M.D. Pediatric Endocrinologists