Gonadotropin levels can discern between hypothalamic hypogonadism, PCOS
One-third of a cohort of women with hypothalamic hypogonadism met Rotterdam criteria for polycystic ovary syndrome when gonadotropin and estrogen levels were not considered, suggesting the hormones should be measured for every woman with anovulation to distinguish between the two conditions, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“It is important to take gonadotropins into account when diagnosing women with anovulatory cycles,” Amoon Alemyar, BS, a medical student at Erasmus University Medical Centre in Rotterdam, the Netherlands, told Healio. “Anti-Müllerian hormone (AMH) levels or sonographic data are not sufficient for the diagnosis. When gonadotropins are not taken into account to classify anovulatory patients, you risk misdiagnosing one-third of the anovulatory women.”
In a retrospective, single-center study, Alemyar and colleagues analyzed data from 3,640 women with PCOS (using Rotterdam criteria), 159 women with hypothalamic hypogonadism and 83 women without anovulation or menstrual cycle disorders (healthy controls) who visited the reproductive endocrinology and infertility clinic at Erasmus University Medical Centre between 1993 and 2018. Researchers age-matched women in the hypothalamic hypogonadism and PCOS groups in a 1:2 ratio to create a second group of 318 age-matched women with PCOS. Researchers assessed blood samples to measure AMH, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, androstenedione and testosterone, and measured ovarian morphology and antral follicle count via transvaginal ultrasound.
The median AMH serum level was 3.8 µg/L for women with hypothalamic hypogonadism, 7.5 µg/L for women with PCOS and 1.9 µg/L for healthy controls. Among the age-matched women with PCOS, the median AMH level was 6.7 µg/L (P < .001).
Women with hypothalamic hypogonadism had an antral follicle count and ovarian volume similar to controls; women with PCOS had an antral follicle count and ovarian volume higher than both groups (P < .001).
Mean SHBG levels were similar for women with hypothalamic hypogonadism and healthy controls (mean, 62.88 nmol/L vs. 71.43 nmol/L, respectively) but lower for age-matched women with PCOS (mean, 45.37 nmol/L); mean androstenedione levels were also similar for women with hypothalamic hypogonadism and healthy controls (mean, 3.05 vs. 3.48, respectively) but higher for age-matched women with PCOS (mean, 6.16).
Testosterone levels for women in the age-matched PCOS group (mean, 1.91 nmol/L) were higher compared with women in the hypothalamic hypogonadism group and the control group (mean, 0.78 nmol/L and 1.15 nmol/L, respectively; P < .001).
Among women with hypothalamic hypogonadism, researchers found that 58 (36%) erroneously met the Rotterdam criteria for PCOS — meeting two of three criteria — if gonadotropin and estrogen levels were not taken into account.
The researchers noted that the observed increase in AMH among women with hypothalamic hypogonadism along with 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, which are undetectable by transvaginal ultrasound.
“A correct distinction between hypothalamic hypogonadism and PCOS is important, as false-positive diagnoses may lead to employment of treatment options that are suboptimal for these women,” Alemyar said. “Gonadotropins should therefore be taken into account for every woman with an anovulatory cycle.”
Alemyar said the role of testosterone, SHBG and androstenedione in women with hypothalamic hypogonadism would be an interesting topic for future research. “In our cohort, we found that more than 10% of women with hypothalamic hypogonadism have clinical hyperandrogenism, but without an obvious increase in free androgen index,” Alemyar said. “Furthermore, biochemical hyperandrogenism is not different from that in the control group. Its etiology may help optimize treatment options for women with hypothalamic hypogonadism.” – by Regina Schaffer
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Amoon Alemyar, BS, can be reached at the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Centre, 3015 GD Rotterdam, the Netherlands; email: amoon.alemyar@gmail.com.
Disclosures: One of the study authors reports he has received fees or grant support during the past 5 years from Danone, Dutch Heart Foundation, Dutch Medical Research Counsel, Euroscreen/Ogeda, Ferring, Netherland Genomic Initiative, Roche Diagnostics and Titus Healthcare. Alemyar reports no relevant financial disclosures.