Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals

Am J Obstet Gynecol. 2021 Jun 12;S0002-9378(21)00685-2. doi: 10.1016/j.ajog.2021.06.052. Online ahead of print.

Abstract

Background: Anti-Müllerian hormone has become the clinical biomarker-based standard to assess ovarian reserve. As anti-Müllerian hormone testing becomes more common, more individuals are seeking to interpret the values obtained while using contraceptives. To appropriately counsel women, a better understanding of anti-Müllerian hormone levels in women using different contraceptives is needed.

Objective: To study the association between different forms of contraceptives and anti-Müllerian levels in women of reproductive age.

Study design: This is a cross-sectional study including 27,125 US-based women aged 20 to 46 years, accessing reproductive hormone results through Modern Fertility and who provided informed consent to participate in the research. Anti-Müllerian hormone levels were collected through dried blood spot card (95.9%) or venipuncture (4.1%), and previous work has shown high correlation between hormone levels collected by these 2 methods. Multiple linear regressions were run to compare anti-Müllerian hormone levels in women using contraceptives with women not on any contraceptive, controlling for age, age of menarche, body mass index, smoking, sample collection method, cycle day, and self-reported polycystic ovary syndrome diagnosis. We also analyzed whether duration of contraceptive use predicted anti-Müllerian hormone levels in users of the hormonal intrauterine device and combined oral contraceptive pill, given the size of these contraceptive groups.

Results: Mean anti-Müllerian hormone levels were statistically significantly lower in women using the combined oral contraceptive pill (23.68% lower; coefficient, 0.76; 95% confidence interval, 0.72-0.81; P<.001), vaginal ring (22.07% lower; coefficient, 0.78; 95% confidence interval, 0.71-0.86; P<.001), hormonal intrauterine device (6.73% lower; coefficient, 0.93; 95% confidence interval, 0.88-0.99; P=.014), implant (23.44% lower; coefficient, 0.77; 95% confidence interval, 0.69-0.85; P<.001), or progestin-only pill (14.80% lower; coefficient, 0.85; 95% confidence interval, 0.76-0.96; P=.007) than women not on any contraceptive when controlling for covariates. Anti-Müllerian hormone levels were not significantly different when comparing women not using any contraceptives to those using the copper intrauterine device (1.57% lower; coefficient, 0.98; 95% confidence interval, 0.92-1.05, P=.600). Associations between contraceptive use and anti-Müllerian hormone levels did not differ based on self-reported polycystic ovary syndrome diagnosis. Duration of hormonal intrauterine device use, but not of combined oral contraceptive pill use, was slightly positively associated with anti-Müllerian hormone levels, although this small magnitude effect is likely not clinically meaningful (coefficient, 1.002; 95% confidence interval, 1.0005-1.003; P=.007).

Conclusion: Current hormonal contraceptive use is associated with a lower mean anti-Müllerian hormone level than that of women who are not on contraceptives, with variability in the percent difference across contraceptive methods. These data provide guidance for clinicians on how to interpret anti-Müllerian hormone levels assessed while on contraceptives and may facilitate more patients to continue contraceptive use while being evaluated for their ovarian reserve.

Keywords: AMH; PCOS; birth control; birth control pill; hormonal IUD; hormonal contraceptives; ovarian reserve.