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Susan Davis, Jane Tran, What Are “Normal” Testosterone Levels for Women?, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 4, 1 April 2001, Pages 1842–1846, https://doi.org/10.1210/jcem.86.4.7436-10
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To the editor:
The cross-sectional study by Laughlin et al. (1), comparing endogenous sex hormones levels with hysterectomy and oophorectomy status, chronological age, and years since menopause in older women, reinforces the possible adverse endocrine sequelae of oophorectomy in older women. However, we question some aspects of the data analysis and, hence, the clinical significance and interpretation of some of the said findings.
The inference from the manuscript is that, in women with intact ovaries, there is an increase in total testosterone levels after the time of menopause and with increasing age reaching premenopausal levels concomitant with falling androstenedione levels. That testosterone should rise while androstenedione falls is incongruous because adrenal androgen precursor levels fall linearly with age (2) and, following the menopause, peripheral conversion of androstenedione becomes a major source of circulating testosterone (3). We would appreciate the authors proposing a hypothesis for this incongruity.
The reason for adjusting total testosterone and bioavailable testosterone for body mass index (BMI) in postmenopausal women is not justified. Because weight may vary significantly with increasing age and years since menopause, and the authors suggest that sex hormone-binding globulin concentrations were inversely related to BMI, one is left to wonder if without adjustment for BMI whether any variation occurred. The authors do not report a relationship between either testosterone or androstenedione and BMI, making the need for the adjustment most curious. Adjustment for BMI is not clinically informative, because the absolute bioavailable circulating levels are the values of physiological significance in terms of direct androgen action and as precursors for extragonadal estrogen biosynthesis in tissues such as bone. Indeed, was a difference seen for bioavailable testosterone not adjusted for BMI? Non sex hormone-binding globulin-bound testosterone includes albumin-bound testosterone, which may account for up to 20% of total testosterone (4). In view of the age of the subjects, if one is to adjust for BMI, surely one should also adjust for variations in serum albumin. Caution in adjusting for covariates in reporting clinical findings has recently been highlighted (5). Presentation of the unadjusted data from this study would be very informative.
