Ovarian reserve markers and endocrine profile during oral contraception: Is there a link between the degree of ovarian suppression and AMH?

Abstract

The ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) are suppressed in varying degree during the use of combined oral contraceptives (COC). Further, long-term use of COC can mask a condition of premature ovarian insufficiency. A desirable clinical tool that could distinguish true low ovarian reserve markers from COC-induced low levels during use of COC is warranted. The aim of this multicenter study including 235 COC users was to assess whether low age-adjusted AMH levels during COC use were linked to concomitant low levels of LH, FSH, estradiol and androgens – as a potential future tool to differentiate between ‘false’, COC-induced low AMH levels vs. true low AMH. Study population and methods: In total, 235 COC users from the general population aged 19–40 years were included. AMH, AFC and a reproductive hormonal profile were measured during COC intake. Age-adjusted AMH levels (Z-scores) were calculated from a comparison group of 983 non-users of COC. Differences in hormonal profile were tested between women with low versus high age-adjusted AMH-quartiles based on non-parametric Wilcoxon rank sum tests. The outcomes of interest were levels of gonadotropins, estradiol and androgens according to the four the age-adjusted AMH quartiles to find out if women with low age-adjusted AMH levels had a stronger gonadotropin suppression compared with women with higher age-adjusted AMH levels. Mean age of COC users was 30.2 years (SD 3.8), median AMH 14 pmol/l (inter-quartile range (IQR) 8.7–23)), median AFC 16 (IQR 11–25). We found no significant differences across the age-adjusted AMH quartiles in either the levels of gonadotropins, estrogens or androgens, respectively. Thus, the degree of suppression of FSH, LH, androgens and estradiol are unlikely to be a useful tool to differentiate between false low and true low ovarian reserve markers during COC use. Presently, there seems to be no alternative to withdrawal of the COC and to re-test the ovarian reserve after 2–3 months.

Trial registration Trial no. NCT02785809 (www.clinicaltrials.gov)

摘要

在服用复方口服避孕药（COC）期间, 卵巢储备功能标志物抗苗勒管激素（AMH）与窦卵泡计数（AFC）会受到不同程度抑制。此外, 长期服用COC会掩盖早发性卵巢功能不全。在使用COC的过程中, 需要一种理想的临床工具来区分真正的卵巢储备功能低下和COC诱导的低水平。此项多中心纳入235名服用COC者, 目的是评估服用COC期间年龄调整后的低AMH水平是否与伴随的低水平的LH、FSH、雌二醇和雄激素有关——作为未来 “假性”、COC诱导的低AMH水平和真性低AMH水平区分的潜在工具。研究人群和方法：在一般人群中纳入235名年龄在19-40岁的口服COC者。在服用COC期间测量AMH、AFC和性激素。年龄调整后的AMH水平(Z值)是从983名未服用COC的对照组中计算出来的。根据非参数Wilcoxon秩和检验, 对年龄调整后的AMH低四分位组和高四分位组的女性之间的激素进行差异比较。令人感兴趣的结果是促性腺激素、雌二醇和雄激素的水平, 根据年龄调整的AMH四分位组来确定：与年龄调整后的AMH水平较高的女性相比, 年龄调整后的AMH水平低的女性其促性腺激素抑制作用是否更强。口服COC者的平均年龄为30.2岁(SD 3.8), AMH中位数为14pmol/l(四分位数间距IQR为8.7∼23), AFC中位数为16(IQR 11∼25)。我们发现, 在年龄调整的AMH四分位组中, 促性腺激素、雌激素或雄激素水平分别没有显著差异。因此, FSH、LH、雄激素和雌二醇的抑制程度不太可能成为在服用COC时假性卵巢储备低下和真性卵巢储备低下区分的有效工具。目前, 除了停用COC并在2-3个月后重新检测卵巢储备外, 似乎别无选择。

试验登记 试验编号.NCT02785809(www.Clinicaltrials.gov)

Keywords:

• AMH
• antral follicle count
• ovarian reserve markers
• oral contraceptives

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS [Grant no. 20200407]. It was also co-financed by Roche Diagnostics. All financing was given as unrestricted grants.