Acne in PCOS

 

While it is impossible to discuss all the causes of acne, and in fact, a great amount of the research that exists is quite varied, much of it implicates excess androgens as the main culprit in the formation of acne. In women, the most common cause of hyperandrogenism (excess androgens) is polycystic ovary syndrome (PCOS).¹

Polycystic ovary syndrome is also associated with hirsutism (excess body hair), hair loss, obesity, irregular menstrual cycles, insulin resistance, skin tags, increase in levels of lipids in the blood and infertility.² Although not all patients with PCOS will exhibit all the signs and symptoms associated with it’s classic picture, even a few of these may prompt you to think of it as a potential offender. If PCOS is indeed suspected in a patient with acne, a proper diagnosis can be attained using ultrasound to evaluate the ovaries, as well as bloodwork.

 

Before we can treat PCOS acne, we must first understand what is at play. Ovarian dysregulation, particularly the upregulation of enzymes that produce androgens in the ovarian theca cells,³ is the hallmark of PCOS. Upon the analysis of the available research, various studies suggest that the exposure of the ovary to bisphenol A (BPA) from ongoing environmental exposure,^4,5 and even during fetal development,⁶ can contribute to polycystic ovaries.  Although environmental exposure is central to it’s development, there are many other factors at hand. Other potential contributors to ovarian dysregulation include prenatal exposure to insulin-like growth factor 1 (IGF-1) and testosterone,⁷ as well as a genetic component. ⁸

 

The stimulatory effects of the androgens and glucose at play in these patients trigger the release of something called tumor necrosis factor (TNF). ^9,10 This powerful inflammatory cytokine is thus found in elevated levels in the ovaries of patients with PCOS.^{9, 10} Unfortunately, this inflammation creates a vicious cycle; inflammation further exacerbates the already upregulated androgenic enzymes found in PCOS, consequently resulting in overproduction of androgens, which in the end cause more inflammation.  The combination of high levels of TNF and inflammation, also produces high levels of oxidative stress and low levels of glutathione.^{11, 12}

 

Insulin resistance, high levels of serum insulin, is also something that can not be overlooked. There is no doubt in the role insulin resistance plays in the PCOS picture. Insulin resistance contributes to the aggravation of the androgen production and inflammation already present, and is also implicated in a slew of other hormonal disturbances. These hormonal disturbances aggravate PCOS and consequently lead to the further production of acne.¹³

 

When discussing the role of hormones, one must also mention the high levels of luteinizing hormones present in PCOS. In PCOS, anovulation results in the production of high levels of luteinizing hormone (LH). In patients with PCOS, LH is 2-3 times higher in comparison to follicle stimulating hormone (FSH).^10,14 It is these high amounts of LH that ultimately drive the ovarian theca cells to produce androgens and in turn halt the release of the follicle (and thus anovulation ensues).

 

Further, IGF-1 is a hormone that is produced mainly in response to growth hormone levels, which are especially high in lean patients with PCOS.¹³ In addition to the growth hormone effect, dairy product consumption¹⁵ and puberty increase IGF-1 levels. Increased IGF-1 is associated with higher 5α-reductase levels, which convert testosterone to dihydrotestosterone, a hormone that stimulates sebum production in patients with acne.¹⁵ Increased sebaceous gland activity can also be due to increased substance P activity documented in individuals with acne.¹⁶ In addition, women with PCOS also have a heightened stress response contributing to further worsening of this picture.¹⁷ These heightened stress levels lead to high levels of cortisol, which in itself will further contribute to acne via it’s role on insulin resistance.

 

…And what can we do?

 

Taking into consideration the multifactorial cause of acne in these patients, one can imagine that the approach to treatment must also be multifaceted.

 

Before anything else, one must build a solid foundation based on modified lifestyle and diet approaches. A whole-foods diet, with the goal of regulating insulin levels should be considered, in addition to eliminating refined grains, sugar, dairy products, and perhaps even gluten. Furthermore, inositol¹⁸ and vitamin D₃¹⁹ have also been implicated in the importance of regulating insulin in PCOS, with low levels of vitamin D₃ being implicated in endocrine disturbances in individuals with this condition.²⁰  It is also essential that the patient with PCOS avoid BPA whenever possible.

 

When discussing lifestyle management, decreasing stress levels is also paramount. Balancing cortisol levels is essential to achieve hormonal balance, especially in patients with PCOS. Mindfulness-based stress reduction techniques are beneficial, as they not only improve quality of life, reduce the symptoms of stress, but also improve the function of the hypothalamus-pituitary-adrenal axis.²¹

 

Botanically, the use of Glycyrrhiza glabra and Paeonia lactiflora have long been shown to potentially reduce testosterone and free testosterone serum levels, increase the ratio of estrogen to testosterone, and decrease the ratio of LH to FSH.²²  In an attempt to further reduce the levels of androgens, recent research suggests that acupuncture, especially using manual needle stimulation, may be effective in lowering said circulating androgen levels in PCOS.²³  G. glabra may be a double threat, as it too, is an excellent adaptogen in this patients and can be used in the management of stress.

 

In addition, we should consider also tackling the ovarian inflammation present.  Epigallocatechin, an extract from green tea, is especially effective in reducing acne in these cases because in addition to reducing ovarian inflammation, it also inhibits 5α-reductase.^{24, 25}

 

 

References

 

1. Timpatanapong P, Rojanasakul A. Hormonal profiles and prevalence of polycystic ovary syndrome in women with acne. J Dermatol. 1997;24(4):223-229.

 

2. Moura HH, Costa DL, Bagatin E, Sodré CT, Manela-Azulay M. Polycystic ovary syndrome: a dermatologic approach [in English and Portuguese]. An Bras Dermatol. 2011;86(1):111-119.

 

3. Wickenheisser JK, Nelson-Degrave VL, McAllister JM. Dysregulation of cytochrome P450 17α-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(3):1720-1727.

 

4. Kandaraki E, Chatzigeorgiou A, Livadas S, et al. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab. 2011;96(3):E480-E484.

 

5. Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y. Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J. 2004;51(2):165-169.

 

6. Fernández M, Bourguignon N, Lux-Lantos V, Libertun C. Neonatal exposure to bisphenol A and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats. Environ Health Perspect. 2010;118(9):1217-1222.

 

7. Veiga-Lopez A, Ye W, Padmanabhan V. Developmental programming: prenatal testosterone excess disrupts anti-Müllerian hormone expression in preantral and antral follicles. Fertil Steril. 2012;97(3):748-756.

 

8. Toulis, KA, Goulis DG, Farmakiotis D, et al. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update. 2009;15(3):297-307.

 

9. González F, Rote NS, Minium J, Kirwan JP. In vitro evidence that hyperglycemia stimulates tumor necrosis factor-α release in obese women with polycystic ovary syndrome. J Endocrinol. 2006;188(3):521-529.

 

10. Gonzalez F, Thusu K, Abdel-Rahman E, Prabhala A, Tomani M, Dandona P. Elevated serum levels of tumor necrosis factor α in normal-weight women with polycystic ovary syndrome. Metabolism. 1999;48(4):437-441.

 

11. Ikeno H, Tochio T, Tanaka H, Nakata S. Decrease in glutathione may be involved in pathogenesis of acne vulgaris. J Cosmet Dermatol. 2011;10(3):240-244.

 

12. Sarici G, Cinar S, Armutcu F, Altinyazar C, Koca R, Tekin NS. Oxidative stress in acne vulgaris. J Eur Acad Dermatol Venereol. 2010;24(7):763-767.

 

13. Morales AJ, Laughlin GA, Bützow T, Maheshwari H, Baumann G, Yen SS. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. J Clin Endocrinol Metab. 1996;81(8):2854-2864.

 

14. Burt Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids. 2012;77(4):332-337.

 

15. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009;18(10):833-841.

 

16. Lee WJ, Jung HD, Lee HJ, Kim BS, Lee SJ, Kim do W. Influence of substance-P on cultured sebocytes. Arch Dermatol Res. 2008;300(6):311-316.

 

17. Benson S, Arck PC, Tan S, et al. Disturbed stress responses in women with polycystic ovary syndrome. Psychoneuroendocrinology. 2009;34(5):727-735.

 

18. Donà G, Sabbadin C, Fiore C, et al. Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome [published online ahead of print January 5, 2012]. Eur J Endocrinol. doi:10.1530/EJE-11-0840. Medline:22223702

 

19. Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D₃treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest. 2011;34(10):757-763.

 

20. Lerchbaum E, Obermayer-Pietsch BR. Vitamin D and fertility: a systematic review [published online ahead of print January 24, 2012]. Eur J Endocrinol. Medline:22275473.

 

21. Carlson LE, Speca M, Patel KD, Goodey E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology. 2004;29(4):448-474.

 

22. Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women. Steroids. 2004;69(11-12):763-766.

 

23. Feng Y, Johansson J, Shao R, Mannerås Holm L, Billig H, Stener-Victorin E. Electrical and manual acupuncture stimulation affects estrous cyclicity and neuroendocrine function in a DHT-induced rat polycystic ovary syndrome model [published online ahead of print February 24, 2012]. Exp Physiol. doi:10.1113/expphysiol.2011.063131. Medline:22337865

 

24. Chen SS, Michael A, Butler-Manuel SA. Advances in the treatment of ovarian cancer: a potential role of antiinflammatory phytochemicals. Discov Med. 2012;13(68):7-17.

 

25. Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone–binding globulin in premenopausal Japanese women. Nutr Cancer. 1998;30(1):21-24.