Association of Selective Serotonin Reuptake Inhibitor Use with Ovarian Reserve Markers and Ovulatory Function in Women Undergoing Fertility Evaluation in Pakistan

Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed in women of reproductive age, yet their potential effects on ovarian reserve and reproductive endocrine function remain uncertain. Limited data are available from low- and middle-income countries, including Pakistan, where psychiatric medication history is not routinely incorporated into fertility evaluation.

Objective: To assess the association between SSRI use and fertility-related hormonal and ovarian reserve markers in women of reproductive age attending the fertility centers.

Methods: This cross-sectional comparative observational study was conducted at multiple fertility centers across Pakistan from January 2025 to June 2025. Fifty women aged 20-40 years undergoing fertility evaluation were enrolled through convenience sampling and divided into two groups: 25 women with major depressive disorder receiving SSRIs for at least 6 months and 25 age-matched controls without psychiatric illness or SSRI exposure. Serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and prolactin were measured, and antral follicle count (AFC) and ovulatory status were assessed. Group comparisons were performed using independent samples t-tests and chi-square tests. Multivariable linear regression was used to evaluate the association between SSRI use and AMH after adjustment for age and body mass index (BMI).

Results: Compared with controls, SSRI users had significantly lower mean AMH (1.8 ± 0.6 vs 3.2 ± 0.9;  ) and AFC (8.4 ± 2.3 vs 12.1 ± 3.1;  ), and significantly higher mean FSH (9.2 ± 2.1 vs 6.8 ± 1.7;  ) and prolactin levels (28.4 ± 6.7 vs 19.6 ± 5.3;  ). LH and estradiol levels were similar between groups. Ovulation was observed in 56% of SSRI users compared with 84% of controls ( ). In multivariable regression, SSRI use remained independently associated with lower AMH ( , SE = 0.32,  ) after adjustment for age and BMI.

Conclusion: SSRI use was associated with lower ovarian reserve markers, higher prolactin and FSH levels, and reduced ovulation in women of reproductive age undergoing fertility evaluation. Although causality cannot be inferred from this cross-sectional design, these findings suggest that SSRI exposure may be linked to altered reproductive endocrine function and warrant further prospective investigation.