Ep 221 – Polyendocrine metabolic ovarian syndrome

Polyendocrine metabolic ovarian syndrome (PMOS) is one of the most common endocrine disorders affecting women of reproductive age, yet it remains widely misunderstood. Although traditionally viewed as primarily a reproductive condition and known as polycystic ovary syndrome, PMOS is now recognised as a complex multisystem disorder with important metabolic, endocrine, dermatological and psychological consequences that extend far beyond the ovaries. In this episode, Dr Roger Henderson explores the underlying pathophysiology of PMOS, including the central role of insulin resistance and hyperandrogenism, as well as the diverse ways patients present in clinical practice. He also reviews the current diagnostic approach, important differential diagnoses and evidence-based management, from lifestyle intervention and pharmacological therapy to fertility treatment and long-term metabolic surveillance.

Key take-home points

• PMOS is one of the most common endocrine disorders affecting women of reproductive age and is increasingly recognised as a lifelong metabolic and endocrine condition rather than simply an ovarian disorder.
• PMOS is highly heterogeneous, with presentations ranging from menstrual irregularity and infertility to acne, hirsutism, hair thinning, insulin resistance and weight gain. No single clinical feature is present in every patient.
• There is no single blood test or imaging study that confirms PMOS. Diagnosis relies on careful clinical assessment, targeted investigations and exclusion of alternative causes.
• Insulin resistance is central to the pathophysiology of PMOS and affects around two-thirds of women, including those with a normal BMI.
• Hyperinsulinaemia stimulates ovarian androgen production and reduces sex hormone-binding globulin, increasing free testosterone. This drives the clinical features of hyperandrogenism, including acne, hirsutism and androgenic alopecia.
• Altered hypothalamic–pituitary–ovarian axis function impairs normal follicular development, leading to anovulation and the characteristic polycystic ovarian morphology seen on ultrasound.
• The polycystic appearance of the ovaries is a consequence of the underlying endocrine disturbance rather than its cause.
• PMOS affects multiple organ systems, increasing the risk of infertility, endometrial hyperplasia, type 2 diabetes, dyslipidaemia, fatty liver disease and cardiovascular disease. Anxiety, depression and reduced quality of life are also significantly more common.
• Diagnosis is based on the presence of at least two of three key features: hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology or elevated anti-Müllerian hormone, after excluding other conditions.
• Important differential diagnoses include thyroid disease, hyperprolactinaemia, congenital adrenal hyperplasia, Cushing syndrome and androgen-secreting tumours. Adolescents require particular diagnostic caution because normal pubertal changes can mimic PMOS.
• Lifestyle intervention is the foundation of management and extends beyond weight loss. Improvements in diet, physical activity, sleep and behavioural health can enhance insulin sensitivity, restore ovulation and improve long-term metabolic outcomes.
• Combined hormonal contraception is first-line treatment for women not seeking pregnancy because it regulates menstrual cycles and reduces androgen excess.
• Metformin improves insulin sensitivity and may restore ovulation, while glucagon-like peptide-1 receptor agonists are emerging as promising options for selected patients with obesity or significant metabolic dysfunction.
• Letrozole is the preferred first-line agent for ovulation induction in women wishing to conceive and should be combined with optimisation of overall metabolic health to improve pregnancy outcomes.
• PMOS requires lifelong follow-up because its clinical manifestations evolve over time, and metabolic risks often persist beyond the reproductive years. Regular monitoring of glucose metabolism, cardiovascular risk factors, endometrial health and psychological wellbeing is an essential component of long-term care.

Key references

1. Teede HJ, et al. Lancet. 2026 May 12. doi: 10.1016/S0140-6736(26)00717-8.
2. Bozdag G, et al. Hum Reprod. 2016;31(12):2841-2855. doi: 10.1093/humrep/dew218.
3. Ding DC, et al. Medicine (Baltimore). 2018;97(39):e12608. doi: 10.1097/MD.0000000000012608.
4. Norman RJ, Teede HJ. Med J Aust. 2018;209(7):299-300. doi: 10.5694/mja18.00635.
5. Forslund M, et al. Eur J Obstet Gynecol Reprod Biol. 2022;271:195-203. doi: 10.1016/j.ejogrb.2022.02.020.
6. Fraison E, et al. Cochrane Database Syst Rev. 2020;8(8):CD005552. doi: 10.1002/14651858.CD005552.pub3.