Hyperandrogenism and Polycystic Ovary Syndrome (PCOS)

The National Institutes of Health (NIH) originally defined polycystic ovary syndrome (PCOS) as a disorder characterized by hyperandrogenism associated with ovulatory dysfunction. Today, PCOS is recognized as the most common endocrine disorder affecting women of reproductive age, with a prevalence of approximately 5–15%, depending on the diagnostic criteria and population studied.

Currently, the Rotterdam criteria (2003) are the most widely accepted diagnostic standard. A diagnosis of PCOS requires the presence of at least two of the following three criteria, after exclusion of other disorders causing androgen excess or ovulatory dysfunction:

  • Oligo-ovulation or anovulation, typically presenting as oligomenorrhea or amenorrhea.
  • Clinical and/or biochemical hyperandrogenism, including manifestations such as acne, hirsutism, androgenic alopecia, or elevated circulating androgen concentrations.
  • Polycystic ovarian morphology (PCOM) on transvaginal ultrasound, characterized by an increased number of small antral follicles and/or increased ovarian volume. Although traditionally referred to as “polycystic ovaries,” these structures are arrested follicles rather than true cysts.

Metabolic Characteristics

Approximately 50–80% of women with PCOS are overweight or obese. Between 30–40% exhibit impaired glucose tolerance, and 8–15% eventually develop type 2 diabetes mellitus. In addition, dyslipidemia, hypertension, metabolic syndrome, and obstructive sleep apnea occur more frequently than in women without PCOS.

A central pathophysiological feature of PCOS is insulin resistance, which is present in approximately 50–70% of affected women, even among those with normal body weight. Compensatory hyperinsulinemia contributes significantly to ovarian androgen excess and reproductive dysfunction.

Pathophysiology of Hyperandrogenism

Hyperinsulinemia amplifies androgen production through several mechanisms:

  • It enhances luteinizing hormone (LH)-stimulated androgen synthesis in ovarian theca cells.
  • It directly stimulates ovarian steroidogenesis independently of LH.
  • It promotes adrenal androgen production to a lesser extent.
  • It suppresses hepatic synthesis of sex hormone-binding globulin (SHBG), thereby increasing circulating free testosterone.

Women with PCOS frequently exhibit elevated LH concentrations and a relatively reduced follicle-stimulating hormone (FSH) level, resulting in an increased LH/FSH ratio, although this finding is no longer considered diagnostic.

Ovarian Steroidogenesis

Within the ovarian follicle, LH stimulates theca cells to synthesize androgens from cholesterol. These androgens diffuse into adjacent granulosa cells, where they are converted into estrogens by the enzyme aromatase under FSH stimulation.

In PCOS, insufficient FSH stimulation reduces aromatase activity, leading to diminished conversion of androgens into estrogens. Consequently, androgen concentrations increase, follicular maturation is arrested, and ovulation fails to occur.

The resulting endocrine abnormalities contribute to:

  • Chronic anovulation
  • Menstrual irregularities (oligomenorrhea or amenorrhea)
  • Hyperandrogenism
  • Clinical signs such as acne, hirsutism, and androgenic alopecia
  • Subfertility or infertility

Pregnancy Complications Associated with PCOS

Women with PCOS have an increased risk of adverse pregnancy outcomes, including:

  • Early pregnancy loss
  • Gestational diabetes mellitus (GDM)
  • Gestational hypertension
  • Preeclampsia
  • Preterm birth
  • Cesarean delivery
  • Fetal macrosomia in pregnancies complicated by diabetes

These risks are largely attributable to insulin resistance, obesity, chronic low-grade inflammation, and metabolic dysfunction. Optimization of body weight and metabolic health before conception significantly improves reproductive and obstetric outcomes.

This image was created using artificial intelligence.Hyperinsulinemia stimulates ovarian androgen production both directly and indirectly through enhanced LH secretion. Simultaneously, insulin suppresses hepatic SHBG production, increasing circulating free androgen concentrations and contributing to the clinical manifestations of hyperandrogenism.

This images were created using artificial intelligence. LH stimulates androgen synthesis from cholesterol in ovarian theca cells. These androgens diffuse into granulosa cells, where aromatase converts them into estrogens under FSH stimulation. Reduced FSH activity in PCOS decreases aromatase-mediated estrogen synthesis, resulting in androgen accumulation, follicular arrest, and chronic anovulation.

References

  1. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Human Reproduction. 2004;19(1):41–47.
  2. International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. 2023 Update. Monash University, ASRM, ESHRE, Endocrine Society et al.
  3. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nature Reviews Disease Primers. 2016;2:16057.
  4. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature Reviews Endocrinology. 2011;7:219–231.
  5. Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction. 2018;33(9):1602–1618.
  6. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2013;98(12):4565–4592.
  7. Fauser BCJM, Tarlatzis BC, Rebar RW, et al. Consensus on women’s health aspects of polycystic ovary syndrome. Human Reproduction. 2012;27(1):14–24.