PCOS Overview
Polycystic ovary syndrome, or PCOS, is an endocrine disorder that is estimated to affect up to 17.8% of reproductive age women.[1] PCOS is characterized in part by enlarged ovaries and multiple follicular cysts, which can be detected by an ultrasound.[2] Additionally, diagnostic criteria include androgen hormone excess in association with chronic oligo-ovulation or anovulation.[3],[4],[5] PCOS is associated with infertility, obesity, type 2 diabetes, and cardiovascular disease.[6],[7],[8] Women with PCOS also report lower quality of life.[9]
PCOS, Adrenal Androgen Excess & DHEA-S
The ovaries are the main source of androgen excess in PCOS. The theca cells of the ovaries produce androgens which are then converted into estradiol by the aromatase enzyme.[10] The ovarian theca cells of PCOS patients secrete surplus androgens, leading to their accumulation.[11] Adrenal androgen excess and adrenal dysfunction is also found in patients with PCOS.[12] In fact, about 20-30% of PCOS patients have adrenal androgen excess.[13],[14] This is generally identified by elevated DHEA-S.[15][16] DHEA-S is the sulfated form of DHEA, an adrenal steroid which is the precursor to both androgen and estrogen sex hormones. The other adrenal androgens are androstenedione and androstenediol.
PCOS and the HPA Axis
Adrenal androgen excess in women with PCOS seems to be linked to HPA axis dysregulation. PCOS patients produce excess pregnenolone and DHEA from the adrenal cortex both at a baseline and in response to pituitary ACTH (adrenocorticotropic hormone).[17]
PCOS patients have also been observed to have increased peripheral metabolism of cortisol.[18],[19] It is hypothesized that PCOS patients may have trouble converting inactive cortisone into cortisol. Thus, activation of the HPA axis to make up for decreased cortisol levels could lead to excess production of adrenal androgens.[20],[21] Furthermore, studies have found that obese patients with PCOS have higher instances of reactive hypoglycemic episodes and increased cortisol secretion late in the day.[22]
PCOS and Insulin Resistance
Why does it matter if women with PCOS have different cortisol patterns or excess androgens? When cortisol is released by the adrenal glands to correct low blood sugar, adrenal androgens, such as DHEA, are also released in PCOS women.[23] The dysregulated adrenal response due to blood sugar instability further contributes to androgen excess.
Androgen imbalance in PCOS patients appears to promote visceral fat accumulation.[24] Adipose tissue is metabolically active and contributes to insulin resistance.[25] Furthermore, increased adipose tissue leads to a decrease in SHBG (sex hormone binding globulin); this allows for a greater amount of testosterone and other androgens to be free in the bloodstream.[26] Thus, there is a vicious cycle of androgen excess leading to weight gain and insulin resistance, which furtherer increases androgen levels in the body.[27]
PCOS Treatment Options
With this in mind, it is clear why PCOS is so closely associated with obesity and type 2 diabetes. So, what are the options for women with this endocrine disorder?
Lifestyle modification, including increased exercise and healthy diet, is generally a first line of defense in PCOS patients, particularly those that are overweight.[28] Estrogen-progestin therapy is also commonly used, usually in the form of birth control pills, to counter-act the effects of excess androgens.[29] Spironolactone is a steroid that blocks the effects of androgens and has some estrogen and progesterone-like effects. Spironolactone is used in PCOS patients, often together with oral contraceptives.[30] Metformin is also used in PCOS patients to increase insulin sensitivity, which can lead to improved blood pressure, cholesterol profiles, and fertility.[31]
For women who prefer complementary and alternative medicine, there are promising options. The herb Cimicifuga racemosa, or black cohosh, has some estrogen-like effects in the body. Multiple randomized, controlled trials found that black cohosh increases fertility in women with PCOS.[32] One study found that women taking black cohosh had even higher fertility rates than women taking clomifene, a pharmaceutical fertility treatment.[33]
Glycyrrhiza spp., or licorice, has androgen-lowering effects in women, and may be a promising complementary therapy for women with PCOS. One clinical trial found that Glycyrrhiza glabra decreased testosterone levels in healthy women.[34] Another clinical trial investigated the effects of Glycyrrhiza glabra in women with PCOS. In this trial, G. glabra was added to a spironolactone treatment regimen.[35] G. glabra reduced the unpleasant side effect of increased androgen levels during the first few days of spironolactone treatment.[36]
Inositol, a naturally occurring sugar alcohol, may help treat several symptoms of PCOS. Studies show that one reason for insulin resistance with PCOS is due to dysfunction in the inositolphosphoglycan (IPG) mediator, a second messenger of insulin.[37] Specifically, a lack of inositol seems to be the cause of IPG mediator dysfunction.[38] Regidor and Schindler observed women with PCOS who took 2000 mg of inositol twice a day. They found that after 3 months, seventy-percent of the women had normalized ovulation.[39] Testosterone levels decreased and progesterone levels increased.[40] The women in the study also achieved pregnancy rates comparable to those attained with metformin, but without negative side effects, such as nausea and diarrhea, and other gastrointestinal issues.[41]
PCOS and Improved Patient Quality of Life
The relationship between PCOS, adrenal dysregulation, androgen excess, and insulin resistance is complex. But it is important to understand so we can help PCOS patients rebalance both adrenal hormones and sex hormones to decrease their risk of obesity and diabetes, and increase their quality of life.
Easily assess adrenal and sex hormones with salivary hormone testing. Find a provider near you or become a provider.
References:
[1] Arentz, S., Abbott, J. A., Smith, C. A., & Bensoussan, A. (2014). Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC complementary and alternative medicine, 14(1), 511.
[2] Baldwin, Constance Y; Selma F. W. (2006) Polycystic Ovary Syndrome. Pediatric Annals; Thorofare 35(12), 888-96.
[3] Pasquali, R., & Gambineri, A. (2012). Cortisol and the polycystic ovary syndrome. Expert Review of Endocrinology & Metabolism, 7(5), 555-566.
[4] Alpañés, M., Fernández-Durán, E., & Escobar-Morreale, H. F. (2012). Androgens and polycystic ovary syndrome. Expert Review of Endocrinology & Metabolism.
[5] Yildiz, B. O., & Azziz, R. (2007). The adrenal and polycystic ovary syndrome. Reviews in Endocrine and Metabolic Disorders, 8(4), 331-342.
[6] Yildiz op.cit.
[7] Alpañés op.cit.
[8] Pasquali op.cit.
[9] Baldwin op.cit.
[10] Alpañés op.cit.
[11] Ibid.
[12] Yildiz op.cit.
[13] Alpañés op.cit.
[14] Pasquali op.cit.
[15] Ibid.
[16] Yildiz op.cit.
[17] Ibid.
[18] Ibid.
[19] Alpañés op.cit.
[20] Ibid.
[21] Yildiz op.cit.
[22] Pasquali op.cit.
[23] Ibid.
[24] Alpañés op.cit.
[25] Ollila, M. M. E., Piltonen, T., Puukka, K., Ruokonen, A., Järvelin, M. R., Tapanainen, J. S., … & Morin-Papunen, L. (2016). Weight gain and dyslipidemia in early adulthood associate with polycystic ovary syndrome: prospective cohort study. The Journal of Clinical Endocrinology & Metabolism, 101(2), 739-747.
[26] Ibid.
[27] Pasquali op.cit.
[28] Baldwin op.cit.
[29] Ibid.
[30] Ibid.
[31] Ibid.
[32] Arentz, S., Abbott, J. A., Smith, C. A., & Bensoussan, A. (2014). Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC complementary and alternative medicine, 14(1), 511.
[33] Ibid.
[34] Ibid.
[35] Ibid.
[36] Ibid.
[37] Regidor, P. A., & Schindler, A. E. (2016). Myoinositol as a safe and alternative approach in the treatment of infertile PCOS women: a German observational study. International journal of endocrinology, 2016.
[38] Ibid.
[39] Ibid.
[40] Ibid.
[41] Ibid.
Clinical Contributor
Marina Braine
Clinical Support Specialist at Sanesco International, Inc.
Marina Braine is a Clinical Support Specialist at Sanesco. She graduated from UNC-Asheville with her Bachelors of Science in Biology with a minor in French. She likes to keep active by hiking, running, and contra dancing around Asheville.
