What is the likelihood of the other two sisters developing Polycystic Ovary Syndrome (PCOS) and endometriosis if their mother and one sister have been diagnosed with these conditions?

Risk of PCOS and Endometriosis in Sisters with Positive Family History

The two unaffected sisters face a substantially elevated risk of developing both conditions, with approximately 5-7 times higher likelihood for endometriosis and likely similar increased risk for PCOS compared to the general population, warranting proactive screening and monitoring.

Familial Risk for Endometriosis

The genetic component of endometriosis is well-established and clinically significant:

• First-degree relatives (sisters and daughters) of women with endometriosis have a 7-fold increased risk (odds ratio 7.2,95% CI 2.1-24.3) of developing the condition compared to women without affected family members 1

• Among patients with confirmed endometriosis, 4.8% of sisters were also affected, compared to only 0.6% of sisters in control groups without endometriosis 1

• The familial tendency is confirmed across multiple studies, with one investigation identifying endometriosis in 6 sisters, 3 aunts, and 2 cousins among 101 patients with the condition, while finding zero cases among control families 2

• Severe manifestations of endometriosis occur more frequently (26% versus 12%, p < 0.01) in patients with a positive family history compared to those without, suggesting not only increased risk but potentially more aggressive disease 1

Familial Risk for PCOS

While the provided evidence focuses primarily on general population prevalence rather than familial clustering:

• PCOS affects approximately 4-13% of women in the general population 3, 4, making it one of the most common reproductive disorders

• The condition has recognized genetic components, though specific familial risk ratios are not detailed in the available guidelines

• Given that one sister and the mother are already affected, this suggests a familial pattern that likely increases risk beyond general population rates

Co-occurrence of Both Conditions

The two conditions can coexist, though they represent distinct pathophysiological processes:

• Among women undergoing gynecologic surgery, approximately 5% had both endometriosis and PCOS, while in the general population this overlap was approximately 2% 5

• Women with both conditions face significantly higher rates of subfertility (adjusted prevalence ratio 10.33,95% CI 3.94-27.08) and chronic pelvic pain (adjusted prevalence ratio 2.53,95% CI 1.07-6.00) compared to those with neither condition 5

• The coexistence rate of 11.83% was found in one laparoscopic study of women with PCOS who were also found to have endometriosis 6

Clinical Implications and Screening Recommendations

Given the substantial familial risk, the unaffected sisters should receive targeted evaluation:

• Maintain high clinical suspicion for symptoms including menstrual irregularities, chronic pelvic pain, dysmenorrhea, dyspareunia, and subfertility, as these may indicate either or both conditions 7, 4, 5

• For PCOS screening: Assess for clinical hyperandrogenism (hirsutism, acne, male-pattern hair loss), menstrual irregularity, and metabolic features including obesity and insulin resistance 8, 4

• For endometriosis screening: Transvaginal ultrasound should be performed if symptoms develop, with sensitivity of 82-90% and specificity of 91-98% for endometriomas 7

• Laparoscopy remains the gold standard for definitive endometriosis diagnosis and should be considered in symptomatic women with strong family history, as imaging may miss small implants 7

• Monitor metabolic health proactively, as both conditions carry increased cardiovascular risk, with screening for hypertension, dyslipidemia, and insulin resistance recommended 8, 4

Important Caveats

• The probability of new endometriosis diagnosis decreases significantly after age 40, so risk is highest during reproductive years 7

• Not all women with familial predisposition will develop these conditions—the 7-fold increased risk for endometriosis still means the majority of at-risk sisters will not develop the disease

• Environmental and lifestyle factors (particularly weight gain) can trigger PCOS development even in genetically predisposed individuals 3

• Early recognition and intervention can significantly improve quality of life and fertility outcomes for both conditions 4, 5