UroToday.com - Prostate and breast cancer appear to be homologous cancer in males and females respectively. Both cancers share hormone etiologies and are treated with hormonal manipulation. The incidence of these two hormone-dependent cancers has steadily risen throughout the twentieth century. Both cancers have race-based links: there is a higher incidence of prostate cancer in African-American men than Caucasian men followed by Asian men and under the age of forty, breast cancer is more lethal in African-American women than Caucasian women and Asian women[1-2] . Beyond genetic and cultural explanations for these differences, an alternative environmental hormone disruptor may be at play as follows.

The cessation of the Woman's Health Initiative (WHI) in July 2002 precipitated a reduction in hormone replacement therapy (HRT) and was followed by a decline in breast cancer incidence in 2003 and 2004 [3] . However, with increasing use of male testosterone replacement therapy there has not been an associated increase in prostate cancer incidence [4] . This suggests the existence of another source of long-term inadvertent and unintentional hormonal exposure common among men and women to support a common etiology between prostate and breast cancer.

This featured abstract reveals an overlooked source of hormones: reservoirs of cutaneous generated hormones and pheromones (androgens), primarily from the "axillary organ" [5] . Apocrine sweat glands are concentrated in the axillae. Estrogen, testosterone, and androgen-based pheromones are contained within these apocrine sweat glands, and nearby cutaneous-aromatase convert testosterone and androstenedione to estradiol and estrone respectively [6-9] . Apocrine sweat secretion is initiated through emotion or stress as well as physical activity. These odor-free secretions become odorous through cutaneous bacterial transformation prompting a currently estimated global annual expenditure of $10 billion on antiperspirants to obstruct the normal function of the axillary organ [10] . Antiperspirants are considered drugs by the United States Food and Drug Administration (FDA) because they affect the function of the body by reducing the amount of sweat that reaches the skin. By not being allowed to reach the skin, the hormonally laden sweat remains on and within the skin, making the antiperspirants potential endocrine disruptors as defined by the United States Environmental Protection Agency (EPA) [11-12] .

Underarm generated hormones and pheromones, which may number greater than one-hundred, are within the optimal molecular weight range of commercially available transdermally-delivered drugs (TDD). The optimum TDD environment is the skin with skin-appendages, (hair follicle; sebaceous, eccrine, and apocrine glands), and is optimal within the axilla [13] . Antiperspirants' possible triggering of "Pharmaceutical" TDD of unintended and inadvertent hormones and pheromones could begin in utero, and continue through the preteen, puberty, and adult years. This chronic, unnatural exposure could occur to developing prostate and breast buds, as well as to mature tissue. Prostate and breast tissues each contain both androgen and estrogen receptors. Plotting breast cancer incidence and mortality against kg/1000 person usage of antiperspirants from 74 countries, reveals positive trend-lines.

The median surface of a single axilla is 64.5 cm2, 135.5 cm2 representing 0.36%, 0.64% of total body surface area in women and men respectively. Underarm product application for females is higher by a factor of 1.6 compared to the median value for males [14] . In Loretz et. al's study, solid- antiperspirant underarm application occurring one to two times delivered an estimated mean 0.79g, with 98.7% of subjects using the product on any given day [15] . Possible explanations for the gender, racial and ethnic prostate and breast cancer epidemiological differences noted above are:
    (1) apocrine sweat glands are more developed and occur more often in women and are larger in African-Americans, followed by Caucasian and Asian individuals [16-17] ; and

    (2) apocrine sweat gland size is less in Asians, larger in whites, and largest in African-Americans.
This may explain prostate cancer incidence at all ages per 100,000 is highest African-Americans 217.5, is next in Caucasians 147.6, and lowest in Asians 83.7. However, this same observation is not seen in breast cancer incidence at all ages per 100,000 where Caucasian is highest with 124.3, next is African-American 116.8, Asian 87.7 is the lowest. However, a trend however is seen when incidence is age-adjusted, ages 20-49. The prostate and breast cancer incidences per 100,000 for ages 20-49 for prostate/breast are: African-American 18.4/72.2, Caucasian 8.2/70, and Asian 1.85/60.9 [1}. Within the context of this concept, sex and hygiene may influence the outcomes with women's apocrine glands being larger and more developed regardless of race, and women applying underarm products more frequently than men.

Through time the underarms have become more occluded as humankind has progressed from hunting and gathering, to farming, to factory work, to office work, with less physical activity via the automobile, and to the desk at a keyboard. And ironically, thermal sweating from physical activity has been usurped by emotional-stress based sweat, potentially affected by daily interference of an underarm endocrine organ by antiperspirants, furthering underarm occlusion and possibly placing men and women in harm's way.

Thus far, circumstantial historical and multi-discipline observations, although persuasive, are insufficient to conclude an etiological link between antiperspirant and prostate and breast cancer. Further confirmatory investigations are required in an effort to eventually offer prevention and reduced incidence and mortality from the world's two most common hormone-dependent cancers.

References

1 - National Cancer Institute. Surveillance epidemiology and end results [accessed 05-20-09].
2 - Donavan M, Tiwary CM, Axelrod D, et al. Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk. Med Hypotheses 2007; 68: 756-766.
3 - Ravdin PM, Cronin KA, Howlander N, et al. The decrease in breast cancer incidence in 2003 in the United States. N Engl J Med 2007; 356(16): 1670-1674. 4 - Raynaud JP. Prostate cancer risk in testosterone-treated men. Steroid Biochem Mol Biol 2006; 102: 261-266.
5 - Grammer K, Fink B, Neave N. Human pheromones and sexual attraction. Eur L Obstet Gynecol Reprod Biol 2005; 118: 135-142.
6 - Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: Basic research and clinical perspectives. J Invest Dermatol 2002; 119: 992-1007. 7 - Rittmaster RS. Androgen conjugates: Physiology and clinical significance. Endocr Rev 1993; 14(1): 121-132.
8 - Zouboulis CC, Chen WC, Thorton MJ, et al. Sexual hormones in human skin. Horm Metab Res 2007;39: 85-95.
9 - Thorton MJ. The biological actions of estrogens on skin. Exp Dermatol 2002; 11: 487-502.
10 - Market sizes. Historical forcast-volume consumption. Antiperspirant kg per '000 people. Chicago, IL: Euromonitor International Inc.; 2008.
11 - Food and Drug Administration. Department of Health and Human Services. Antiperspirant drug products for over-the-counter human use; final monograph. Federal Register 2003; 68:34273-34293.
12 - National Center for Environmental Research. United States Environmental Protection Agency. What are endocrine disruptors?.
13 - Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv 2004; 4: 308-312.
14 - Cowan-Ellsberry CMcNamee, Leazer T. Axilla surface area for males and females: Measured distribution. Regulatory Toxicol and Pharmacol 2008; 52: 46-52.
15 - Loretz L, Api AM, Barraj L, et al. Exposure data for personal care products: Hairspray, spray perfume, liquid foundation, shampoo, body wash, and solid antiperspirant. Food and Chem Toxicol 2006; 44: 2008-2018.
16 - McGrath KG. Apocrine sweat gland obstruction by antiperspirants allowing transdermal absorption of cutaneous generated hormones and pheromones as a link to the observed incidence rates of breast and prostate cancer in the 20th century. Med Hypotheses 2009; 72: 665-674.
17- Hurley HJ, Shelly WB. Introduction,The nature of apocrine sweat, Disorders of the apocrine gland. In: Hurley HJ, Shelly WB eds. The human apocrine sweat gland in health and disease. Springfield, IL: Thomas; 1960: pp 3-9, 76-99.

Written by Kris G. McGrath, MD as part of Beyond the Abstract on UroToday.com.

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