Anti-Müllerian Hormone and Ovarian Morphology in Women With Hypothalamic Hypogonadism

Abstract

Context Different phenotypical features of women with hypothalamic hypogonadism (HH), also known as World Health Organization-1 anovulation, including ovarian morphology, have been scarcely described in large cohorts. Some studies have reported increased levels of anti-Müllerian hormone (AMH) in women with HH. Objective To assess whether women with HH, compared with healthy controls, have increased serum levels of AMH and what proportion of these women erroneously meet the Rotterdam Criteria for Polycystic Ovarian Syndrome (PCOS). Design, Setting and Participants Retrospective cohort study in a Dutch academic medical center including 83 women with neither anovulation nor menstrual cycle disorders (healthy controls), 159 women with HH and 3640 women with PCOS. Age matching was used between the HH and PCOS group (1:2 ratio) to create a second group consisting of 318 age-matched women with PCOS. Intervention None. Main outcome measures AMH levels and ovarian morphology. Results Median AMH serum levels for the HH group were 3.8 (<0.1–19.8), compared with 7.5 (<0.1–81.0) in the PCOS group and 1.9 (<0.1–21.5) in the control group (P < 0.001). In the HH group, 58 (36%) erroneously met the Rotterdam Criteria for PCOS (meeting 2 of 3 criteria). Conclusions AMH levels are increased in women with HH. We hypothesize that this increase, although there was no increase in follicle count, may be explained by the presence of a relatively large pool of antral follicles smaller than 2 mm in diameter, that are undetectable by transvaginal ultrasound. This study highlights the importance of measuring gonadotropins and estradiol before diagnosing a patient with PCOS.

Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)

“…25 Testosterone was higher in PCOS (1.95 ± 1.04) than in controls (1.15 ± 0.5), or FHA (0.78 ± 0.42). 65 Similarly, androstenedione levels were 6.14, 3.48 and 3.05 nmol/L and the Ferriman-Gallwey scores were 7.29, 3.45 and 4.64, respectively. 65 Women with AN have reduced 5-alpha-reductase activity, 110 whereas women with PCOS have increased 5-alpha-reductase activity, 111 such that pending further data, a 'DHEA challenge test' could potentially be used to distinguish these conditions.…”

“…75 AMH was higher in age-matched women with PCOS (47.9 pmol/L), than in FHA (27.1 pmol/L) and in healthy women (13.6 pmol/L). 65 In 1843 women with oligo/amenorrhoea, AMH was higher in the 69% with PCOS (65 pmol/L) than in the 7% with FHA (24.3 pmol/L). 76 Collectively, AMH levels are markedly elevated in PCOS; however, milder increases are also seen in FHA.…”

“…64 In PCOS (n = 3640), FHA (n = 159) (defined by gonadotrophins <2 iU/L) and healthy controls (n = 83), LH was 9.6, 0.8 and 3.8 iU/L, FSH was 5.6, 3.1 and 6.3 iU/L and oestradiol was 279, 72 and 170 pmol/L, respectively. 65 Notably, LH was more commonly raised in PCOS if associated with menstrual disturbance. 66 An LH:FSH ratio of 1.33 had an AUROC curve of 0.87 (95% CI 0.84-0.89) to distinguish PCOS from healthy controls, with a one unit increase in the ratio increasing the odds of PCOS by 14-fold.…”

“…108 In a direct comparison, SHBG levels were 47, 63 and 71 nmol/L in PCOS, healthy controls and FHA, respectively. 65 Thus, free androgen index (FAI) is likely to better differentiate FHA and PCOS than unadjusted testosterone levels.…”

“…Therefore, these thresholds should be regarded as indicative pending further study in which these parameters are directly compared in women with amenorrhoea in the same study. Polycystic ovarian morphology (PCOM) was defined as having at least one ovary with 12 or more follicles per ovary and odds of PCOS diagnosis calculated by univariate logistic regression 66 …”