These cases of ovulatory dysfunction are linked to infertility and menstrual disturbances. A post hoc analysis from a randomized, placebo-controlled, multi-centre study carried out at 11 secondary care centres, as well as a longitudinal single-centre study on pregnant women in Norway, also determined that metformin had no effect on maternal androgens in pregnancies occurring in the setting of PCOS.One systemic review suggested that polymorphisms in the vitamin D receptor gene are associated with the prognosis of polycystic ovary syndrome, though this is based on small sample sizes and is debated. Studies have shown benefits for vitamin D supplementation in women with vitamin D deficiency and PCOS.Hyperinsulinemia can increase the production of androgens in the ovaries. One context in which this occurs is HAIR-AN syndrome, a rare subtype of PCOS. Hyperthecosis and hyperinsulinemia
Hyperthecosis occurs when the cells of the ovarian stroma transition from interstitial cells, located between other cells, into luteinized theca cells. Theca cells are located in the ovarian follicles and become luteinized when the ovarian follicle bursts and a new corpus luteum is formed. The dispersal of luteinized theca cells throughout the ovarian stroma — in contrast to their distribution in PCOS, in which luteinized theca cells occur around cystic follicles only — causes women with hyperthecosis to have higher testosterone levels and virilization) than women with PCOS. Elevated insulin is also characteristic of hyperthecosis. Hyperthecosis most commonly develops in postmenopausal women and is linked to acne, hirsutism, growth of the clitoris, baldness, and voice deepening.Obesity can play a role in insulin resistance.
Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to reduce androgenic signaling. For hyperandrogenism caused by late-onset congenital adrenal hyperplasia (LOCAH), treatment is primarily focused on providing the patient with glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the increase in size of the adrenal glands. Estrogen-based oral contraceptives are used to treat both LOCAH- and PCOS-associated hyperandrogenism. These hormonal treatments reduce the androgen excess and suppress adrenal androgen production, bringing about a significant decrease in hirsutism.Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60–100% of patients reporting an improvement in hirsutism. Androgenic alopecia however, does not show an improvement with hormonal treatments and requires other treatments, such as hair transplantation.Supplementation can also contribute to the managing the symptomatic effects of hyperandrogenism. In a meta-analysis, high-dose vitamin D supplements given to women with vitamin D deficiency due to PCOS improved glucose levels, insulin sensitivity, and cholesterol levels, as well as lowering testosterone, sex hormone-binding globulin, and the free androgen index, all of which are associated with hyperandrogenism. Vitamin D supplementation in women with vitamin D deficiency but without PCOS did not show the same results. Targeting insulin resistance and obesity
Lifestyle modifications are the first-line treatment for PCOS. They help improve body composition, insulin resistance, and hyperandrogenism. However, it is unclear whether they help improve mood, quality of life, and reproductive outcomes.