Women with Turner syndrome have decreased levels of testosterone, free androgen index, androstenedione, and dihydroepiandrosterone sulfate (DHEAS) compared with women without Turner syndrome, according to the results of a study published in the Journal of Clinical Endocrinology & Metabolism.

Investigators sought to evaluate the levels and pattern of sex hormones in women with Turner syndrome with use of standard statistical tests and unsupervised principal component analysis.

A total of 99 women with Turner syndrome and 68 healthy, age-matched women (control individuals) were followed from August 2003 to February 2010. The women with Turner syndrome underwent 3 visits (visits A, B, and C) within 4 to 5 years, and the women in the control group underwent 1 visit (visit B). At visit B, 74 women with Turner syndrome received hormone replacement therapy (HRT) and 15 were untreated. Estrogen and androgen levels were measured 7 to 9 times across menstruation cycles.


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Data from 28 eumenorrheic women (mean age, 23.8±2.7 years; body mass index [BMI], 22.9±2.7 kg/m2) were also included to show the normal fluctuation of sex hormone levels across the menstruation cycle.

The cross-sectional analysis (visit B) included 89 women with Turner syndrome (median age, 41 [21-64] years) and 68 age-matched and sex-matched control individuals (median age, 39 [range, 19-63] years).

All androgens — testosterone, free androgen index, androstenedione, and DHEAS — were found to be approximately 30% to 50% lower in the women with Turner syndrome vs the women in the control group. In addition, circulating levels of 17-OH progesterone and sex hormone-binding globulin (SHBG) were decreased in women with Turner syndrome. Circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrone sulfate were more than doubled in women with Turner syndrome compared with women in the control group. Levels of 17β-estradiol were comparable among both groups.

Increased FSH (P =.036) and LH (P =.042) and decreased 17β-estradiol (P =.017) and estrone sulfate (P <.01) were observed in women with Turner syndrome who did not receive HRT vs those who received HRT. Androgen and SHBG levels were comparable among both groups.

A principal component analysis assessing the intergroup and intragroup correlations of sex hormones in women with Turner syndrome found that testosterone, free androgen index, FSH, and LH concentrations were most likely to differentiate between women with Turner syndrome and women in the control group.

Among several study limitations, the investigators were not able to match women with Turner syndrome and women in the control group according to BMI. Also, blood samples for sex hormone concentrations were drawn randomly and independent of menstrual cycle in the women with Turner syndrome and in women in the control group, and there may be discrete differences between the HRT and non-HRT groups that were not accounted for.

“Androgens, in addition to estrogens, are reduced in Turner syndrome and can be used to discriminate them from female controls,” concluded the researchers. “HRT-treated [women with Turner syndrome] only reach the early follicular phase estrogen level of an eumenorrheic woman. Principal components analysis applied to the sex hormone levels in Turner syndrome reveals a picture of androgen deficiency aggravated further by use of HRT.”

Reference

Hansen Viuff M, Just J, Brun S, et al. Women with Turner syndrome are both estrogen and androgen deficient — the impact of hormone replacement therapy. J Clin Endocrinol Metab. Published online March 18, 2022. doi:10.1210/clinem/dgac167