Polycystic Ovarian Syndrome (PCOS)
A 22-year-old woman presents to her GP with irregular menstrual bleeding. Her menses occur every 3-4 months, with her last menstrual period occurring 7 weeks ago. She is not sexually active. Physical exam shows a high BMI and hair on her upper lip. Serum studies show raised testosterone and LH. What is your likely diagnosis?
To truly understand the pathophysiology of PCOS, let’s first revise the basic roles of hormones in endocrine regulation of the menstrual cycle. As a quick summary, GnRH is released from the hypothalamus, stimulating the release of LH and FSH from the anterior pituitary gland to mature the follicle. However, the follicle initially releases estrogen and inhibin to negatively feedback to the hypothalamus, ensuring GnRH, and thus LH and FSH stay low. However, an LH surge causes ovulation to occur, progressing the follicle to the corpus luteum. The corpus luteum releases estrogen, inhibin, and progesterone, negatively feeding back to keep LH and FSH at the correct ratios.
Ok, so in PCOS, ovulation is prevented, decreasing progesterone in the luteal phase. As such, negative feedback is reduced, increasing GnRH pulse frequency. LH is more responsive to this increased GnRH pulse frequency; thus, LH is greatly increased. This imbalance of LH and FSH impairs follicle maturation leading to anovulation and infertility. Additionally, the increase in LH stimulates the production of androgens. This androgen production decreases insulin sensitivity; thus, the body increases insulin production to compensate. This leads to insulin resistance, creating a vicious cycle where androgen production is even further stimulated.
Ok, so now that we understand the pathophysiology, the symptoms of PCOS are super easy to understand too. Symptoms include hirsutism and acne through excess androgens, menstrual irregularity, infertility, and metabolic syndrome.
In terms of diagnosis, the Rotterdam criteria must be satisfied. This is done through satisfying 2 of these 3 criteria, including oligo-ovulation or anovulation, hyperandrogenism, and enlarged and/or polycystic ovary on US (that show ovarian volume of >10 mL or multiple cystic follicles). A complication of PCOS is endometrial cancer. This occurs through unopposed estrogen (as a result of decreased progesterone) during anovulatory cycles, leading to endometrial hyperplasia and thus increasing the risk of endometrial cancer.
To treat PCOS, a COCP is our first-line drug for androgen suppression and menstrual irregularities. Metformin is used to improve menstrual irregularities, metabolic outcomes, and weight. Antiandrogen drugs such as spironolactone have a controversial role and are mostly used in patients who cannot tolerate a COCP. It is important to note, however, in patients trying to conceive living with PCOS, the gold standard drug is letrozole to induce ovulation.