What is the most likely cause of prolonged menstrual bleeding in a 20‑year‑old woman with bilateral polycystic ovarian syndrome?

Prolonged Menstruation in PCOS: Anovulatory Bleeding from Unopposed Estrogen

The most likely cause of prolonged menstrual bleeding in a 20-year-old woman with bilateral PCOS is chronic anovulation leading to unopposed estrogen stimulation of the endometrium, which results in irregular endometrial proliferation and breakthrough bleeding. 1, 2

Pathophysiology of Prolonged Bleeding in PCOS

The fundamental mechanism involves:

• Chronic anovulation prevents progesterone production from a corpus luteum, eliminating the normal secretory transformation and organized shedding of the endometrium 3, 4
• Unopposed estrogen exposure causes continuous endometrial proliferation without the stabilizing effect of progesterone, leading to irregular, unpredictable breakdown and prolonged bleeding episodes 1, 4
• This pattern represents anovulatory abnormal uterine bleeding rather than true menstruation, as no ovulation has occurred 4

The excessive androgen secretion characteristic of PCOS disrupts normal ovulatory cycles, with many women experiencing severe oligoovulation or complete anovulation 3, 5. This hormonal imbalance creates a state where estrogen continuously stimulates endometrial growth without the cyclical progesterone withdrawal that normally triggers organized menstrual shedding 6.

Critical Health Implications

Beyond the immediate bleeding concern, this pattern carries serious risks:

• Endometrial hyperplasia and cancer risk increases significantly with prolonged unopposed estrogen exposure 1, 4
• Women with PCOS and amenorrhea or irregular bleeding for more than 3 months require immediate endometrial protection 1, 2
• The risk escalates with duration of anovulation, making prompt intervention essential 1

Diagnostic Approach

To confirm anovulation as the cause:

• Mid-luteal progesterone (cycle day 21-23 or 7 days before expected menses) with levels <6 nmol/L confirms anovulation 7
• Exclude other causes including thyroid dysfunction (TSH), hyperprolactinemia (prolactin), and coagulation disorders (particularly von Willebrand disease in cases of true menorrhagia) 7, 4
• Endometrial assessment is indicated if the patient is ≥35 years old, has risk factors for endometrial cancer, or has bleeding unresponsive to initial medical therapy 4

Treatment Algorithm

First-line treatment for women not seeking pregnancy:

• Combined oral contraceptive pills (COCPs) are the cornerstone therapy, as they regulate menstrual cycles, provide endometrial protection against unopposed estrogen, and reduce intermenstrual bleeding 2, 3
• COCPs work by suppressing ovarian androgen secretion, increasing sex hormone binding globulin, and providing regular progesterone withdrawal 2

Alternative if COCPs are contraindicated:

• Cyclic progestin therapy (such as medroxyprogesterone acetate) for 10-14 days per month provides endometrial protection and induces regular withdrawal bleeding 1, 2, 3
• This ensures at least quarterly endometrial shedding to prevent hyperplasia 1

Adjunctive therapy:

• Metformin may improve ovulation rates in women who cannot take combined hormonal contraception, particularly those with metabolic abnormalities 3
• Lifestyle modification with even 5-10% weight loss can restore menstrual regularity in overweight/obese women with PCOS 2

Common Pitfalls to Avoid

• Do not delay endometrial protection in women with prolonged anovulatory bleeding, as the cancer risk increases with duration of unopposed estrogen exposure 1
• Do not confuse anovulatory bleeding with ovulatory menorrhagia (true heavy menstrual bleeding with ovulation), which has different causes including structural lesions and coagulation disorders 4
• Do not assume all irregular bleeding in PCOS is benign—women ≥35 years or those with risk factors require endometrial biopsy before initiating hormonal therapy 4
• Do not overlook functional hypothalamic amenorrhea as an alternative diagnosis, particularly in underweight women or those with excessive exercise, as this requires different management despite potentially showing polycystic ovarian morphology on ultrasound 8

The distinction between PCOS-related anovulation and functional hypothalamic amenorrhea can be challenging, as both may present with polycystic ovaries on imaging 8. However, PCOS typically presents with normal or elevated estrogen levels causing breakthrough bleeding, while functional hypothalamic amenorrhea presents with low estrogen and amenorrhea 8.