PCOS: Phenotypes, Mechanisms and the Role of Insulin

Polycystic ovary syndrome is misnamed in 2 ways. Its defining feature is not cysts, which are in fact arrested follicles, and it is not solely an ovarian disorder but a systemic condition affecting metabolism, the skin, fertility, mental health and long term cardiometabolic risk. It is common, frequently diagnosed late, and often managed in fragments, with one practitioner treating irregular periods, another acne and a third weight. An integrated understanding brings these threads together.

Diagnosis

The international evidence based guideline, most recently updated in 2023, supports the Rotterdam criteria. In adults, PCOS is diagnosed when 2 of the following 3 are present, after exclusion of other conditions:

1. Ovulatory dysfunction: irregular or absent menstrual cycles.
2. Hyperandrogenism: clinical signs, such as hirsutism, acne or androgenic hair loss, or raised androgen levels in blood.
3. Polycystic ovarian morphology on ultrasound, or raised anti Müllerian hormone. The 2023 guideline allows AMH as an alternative to ultrasound in adults.

In adolescents, diagnosis requires both irregular cycles and hyperandrogenism, because irregular cycles and multifollicular ovaries are normal in the years after menarche. Ultrasound and AMH are not recommended for diagnosis in this age group.

Conditions that can mimic PCOS must be excluded, including thyroid disease, raised prolactin, non classic congenital adrenal hyperplasia and, where clinical features suggest them, Cushing syndrome or androgen secreting tumours.

Phenotypes

Phenotype helps predict risk and guide priorities, but individual assessment matters more than category.

Mechanisms

Insulin resistance and hyperinsulinaemia

Insulin resistance is present in most women with PCOS, including many who are lean, and is worsened by excess weight. High insulin levels stimulate the ovaries to produce more androgens and reduce the liver’s production of sex hormone binding globulin, increasing free, active androgen. This creates a cycle in which metabolic and reproductive features reinforce each other.

Neuroendocrine changes

Altered pulsatile secretion of gonadotrophin releasing hormone increases luteinising hormone relative to follicle stimulating hormone, further stimulating ovarian androgen production and impairing follicle development.

Ovarian factors

Ovarian theca cells in PCOS produce more androgens intrinsically, and follicles arrest before ovulation.

Genetics and development

PCOS runs in families and has substantial heritability. Prenatal androgen exposure has been proposed as a developmental contributor.

Inflammation

Chronic low grade inflammation is commonly present and may contribute to both metabolic and ovarian features.

Beyond fertility: long term risks

The international guideline recommends assessing glycaemic status at diagnosis and periodically thereafter, with an oral glucose tolerance test preferred in higher risk women, and screening for depression, anxiety and disordered eating.

Lean PCOS

PCOS is not confined to women with obesity. Lean women with PCOS often have insulin resistance too, though usually less marked, and their diagnosis may be delayed because they do not fit the expected picture. Weight loss advice is inappropriate for them; attention to diet quality, exercise and sleep remains relevant.

Management by priority

Lifestyle

Lifestyle intervention is recommended for all women with PCOS. In women with excess weight, loss of 5 to 10 percent can improve cycle regularity, ovulation, androgen levels and metabolic markers. No single diet has been shown superior; a balanced, lower glycaemic, fibre rich pattern that the woman can sustain is appropriate. Regular aerobic and resistance exercise improves insulin sensitivity independently of weight loss. Given the high prevalence of disordered eating in PCOS, weight focused advice must be delivered sensitively, and restrictive approaches avoided.

Menstrual regulation and androgen features

Combined oral contraceptives regulate cycles, protect the endometrium and reduce hirsutism and acne. Anti androgens and cosmetic treatments address hirsutism. Cyclical progestogens protect the endometrium in women who do not want hormonal contraception.

Metabolic features

Metformin improves metabolic markers and may help cycle regularity and weight, particularly in women with higher BMI. Newer weight management medicines are being studied and used in PCOS with excess weight.

Fertility

For ovulation induction, letrozole has become first line, having produced higher live birth rates than clomiphene in a large trial. Specialist fertility care follows where needed.

Inositol

Myo inositol and related compounds have some trial evidence for metabolic and ovulatory outcomes. The 2023 guideline considers the evidence limited and inconsistent, but notes that inositol may be considered by women who wish to try it, with appropriate discussion.

A functional approach

The timeline often shows irregular cycles from adolescence, weight gain at particular life stages and a family history of PCOS or diabetes. Mediators commonly include refined carbohydrate intake, inactivity, poor sleep, stress and, in some women, sleep apnoea. The matrix connects communication, energy and defence and repair. A plan built from these, with attention to the woman’s own priorities, whether fertility, acne, cycles, weight or energy, is more likely to succeed than a generic one.

An illustrative case

A 27 year old woman with irregular cycles since her teens, acne and hirsutism has a BMI of 23. She was told her weight was normal and she could not have PCOS. Blood tests show raised testosterone and a low SHBG; an ultrasound shows polycystic morphology. An oral glucose tolerance test reveals impaired glucose tolerance despite her normal weight. She is diagnosed with PCOS, phenotype A.

Her priorities are her skin and future fertility. With her doctor, she starts a combined oral contraceptive for cycle control and skin. Her plan includes resistance training, a protein and fibre rich breakfast, reduced sugary drinks and a regular sleep schedule. She is screened for anxiety and body image concerns, which she appreciates. A year later her acne has improved and her glucose tolerance has normalised. When she decides to try for a pregnancy, her care will change accordingly.

A lifelong condition

PCOS is not only a reproductive problem to be addressed when fertility is desired. It is a lifelong metabolic and hormonal condition that deserves early diagnosis, attention to mental health and long term cardiometabolic care, tailored to each woman’s phenotype and goals.