Polycystic Ovary Syndrome and Hormones
How Testosterone, Insulin, and Progesterone Affect PCOS
Written by Hershil Parekh, RPh – Women’s International Pharmacy
Have you struggled with excessive hair growth and acne, difficulty getting pregnant, weight gain, and chronic menstruation irregularities for most of your life? If you answered “Yes” to any of the above symptoms, you may be one of the 4-8% of women across the globe who suffers from Polycystic Ovary Syndrome (PCOS). It is often considered to be the most common endocrine disorder suffered by women of childbearing age in the United States. With no clear underlying cause, PCOS is a complex disorder encompassing many organ systems.
PCOS is usually diagnosed when a patient exhibits one or more the following symptoms:
- High circulating testosterone levels
- The presence of ovarian cysts (though contrary to what the name “Polycystic Ovary Syndrome” suggests, it’s possible to have PCOS without ovarian cysts)
- Menstrual irregularities that lead to the inability to ovulate
Imbalances of the hormones testosterone, insulin, and progesterone play a critical role in the various symptoms of PCOS and the other conditions that may be associated with it. Managing PCOS involves treating these symptoms with lifestyle modifications and medications.
Understanding the HPG Axis and Its Role in Fertility
Regulation of the reproductive system starts in the hypothalamic-pituitary-gonad (HPG) axis. The HPG axis begins with the hypothalamus producing gonadotropin-releasing hormone (GnRH), which is then released in pulses to hormone receptors on the anterior pituitary gland. Depending on the rate of stimulation it receives, the anterior pituitary gland produces one of two gonadotrophic hormones: follicle stimulating hormone (FSH) or luteinizing hormone (LH).
- During a woman’s menstrual cycle, FSH plays a key role in the growth and maturation of the ovarian follicle (a small fluid-filled sac in the ovary containing an immature egg) and estradiol production.
- LH is responsible for the rupture of the mature ovarian follicle which releases an ovum for fertilization as well as the production of estradiol (in the first two weeks of the cycle) and testosterone and progesterone.
Abnormalities in LH and FSH production may lead to the inability to ovulate and also increases in testosterone production and decreases in progesterone production.
Hormonal Influences on PCOS Symptoms
Many of the problems associated with PCOS revolve around hormonal imbalances of testosterone, insulin, and progesterone.
PCOS and Testosterone
Testosterone is one of the many sex hormones made via the HPG axis and is considered an androgenic sex hormone. Androgens (from the Greek andro, meaning “male”) are found in higher concentrations in men than in women, and play a role in the development of male characteristics. Testosterone is produced when the reproductive system is stimulated by LH.
PCOS patients present with many adverse reactions associated with abnormally high testosterone levels:
- Hirsutism (the growth of long, coarse, dark hair), develops in androgen-sensitive areas such as the chest, upper lip, chin, back, and abdomen.
- Acne is caused in these androgen-sensitive areas when sebaceous glands in the skin begin to overproduce sebum (an oily substance secreted to moisturize the skin).
- In hair follicles on the scalp, testosterone is broken down into dihydrotestosterone and results in male-pattern balding.
Another hormone called insulin exacerbates these symptoms when not utilized properly by the body.
PCOS and Insulin
Insulin is a metabolic hormone that helps the body exploit its main fuel source, glucose. PCOS patients commonly suffer from a weight-related metabolic condition called insulin resistance, where the body is not sensitive to insulin spikes after the consumption of food. Insulin is needed to help glucose penetrate cells of the body from the blood.
Poor utilization of insulin increases its levels in the blood and this may lead to increased testosterone in several ways:
- Insulin may promote GnRH production in the hypothalamus, causing a more frequent stimulation of the anterior pituitary gland, which increases LH levels.
- Insulin may also directly stimulate cells in the ovaries to produce more androgens.
Insulin may indirectly reduce transport proteins (called sex hormone binding globulin) which shuttle testosterone in the body. This increases the free testosterone that is available to circulate and activate receptors anywhere in the body and amplifies the testosterone response throughout the body.
PCOS and Progesterone
Dr. Jerilynn Prior, a Professor of Endocrinology and Metabolism, has spent her career studying menstrual cycles and the effects of the cycle’s changing estrogen and progesterone hormone levels on women’s health. She explains:
Progesterone is the hormone made by the ovary after an egg is released. Patients with [PCOS] have sporadic or absent ovulation, so they are not making progesterone for two weeks every cycle. This lack of progesterone leads to an imbalance in the ovary, causes the stimulation of higher male hormones, and leads to irregular periods and trouble getting pregnant. Progesterone is usually missing—replacing it therefore makes sense.
In an article for Gynecological Endocrinology, Dr. Helen Buckler et al. write that progesterone appears to normalize the heightened LH levels associated with PCOS. Raised LH is one of the mechanisms that stimulate testosterone production. In addition, Dr. Prior notes that progesterone inhibits the enzyme that allows testosterone to convert into dihydrotestosterone, the androgen that contributes to acne, hirsutism, and (as mentioned previously) male pattern baldness.
Treatment Options for PCOS
Multiple treatment options are available to control PCOS symptoms. Traditionally, PCOS has been treated with an array of medications that inhibit androgen hormones through various mechanisms. However, using progesterone in bioidentical hormone therapy is one alternative that replenishes progesterone levels and encourages the regulation of androgen production in a way more natural to the body.
- The anti-diabetic agent Metformin and a class of cholesterol-lowering medications called statins may be used for managing metabolism.
- Anti-androgens (such as finasteride) may be used to control circulating testosterone levels and hirsutism.
- Patients experiencing irregular menstrual cycles may be prescribed oral contraceptives containing progestins. However, synthetic progestins themselves may have negative effects on a woman’s health.
- Clomiphene citrate may be used to induce ovulation in patients who are having difficulty getting pregnant.
- Compounded bioidentical progesterone may have a variety of benefits in the treatment of PCOS and its symptoms. According to Dr. Prior, progesterone signals to the HPG axis when to stop production of androgens, which prevents testosterone overproduction. If progesterone deficiency is addressed by supplementing compounded bioidentical progesterone for two weeks every month, it “may help the brain develop the normal cyclic rhythm that is missing in PCOS.”
- Weight reduction with the help of a calorie-restricted diet and exercise is recommended to help decrease androgen levels and control glucose and insulin levels.
Controlling PCOS often requires a multifaceted approach. Treating individual symptoms decreases the development of associated conditions such as type 2 diabetes, cardiovascular disease, infertility, and endometrial cancer. Meanwhile, a combination of medications and healthy lifestyle habits may be used to address any underlying hormone imbalances that may exacerbate PCOS in the first place.
- Buckler HM. Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome. Gynecol Endocrinol. 1992 Dec;6(4):275-82.
- El Hayek S, et al. Poly Cystic Ovarian Syndrome: An Updated Overview. Front Physiol. 2016 Apr 5;7:124. , doi:10.3389/fphys.2016.00124. eCollection 2016.
- Follicle Stimulating Hormone.You and Your Hormones, http://www.yourhormones.info/hormones/follicle-stimulating-hormone/. Reviewed Feb 2018. Accessed April 2019.
- Luteinising Hormone.You and Your Hormones, http://www.yourhormones.info/hormones/luteinising-hormone/. Reviewed Feb 2018. Accessed April 2019.
- Prior, JC. Help for Anovulatory Androgen Excess (AAE)—Challenge PCOS! Cemcor. http://www.cemcor.ubc.ca/resources/help-anovulatory-androgen-excess-aae%E2%80%94challenge-pcos. Updated November 29, 2013. Accessed April 2019.
- Rojas J, et al. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int J Reprod Med. 2014;2014:719050. doi: 10.1155/2014/719050. Epub 2014 Jan 28.
- Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016 Oct;37(5):467-520. Epub 2016 Jul 26.
- Tsutsumi R, Webster NJ. GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr J. 2009;56(6):729-37. Epub 2009 Jul 17. Vadakkadath MS, Atwood CS. The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain. Cell Mol Life Sci. 2005 Feb;62(3):257. https://doi.org/10.1007/s00018-004-4381-3