Polycystic ovary syndrome (PCOS), one of the most common gynecologic disorders of reproductive-aged women, involves menstrual disturbances, chronic anovulation, and hyperandrogenism1,2 and is frequently accompanied by insulin resistance and hyperinsulinemia.3,4 Hyperandrogenism is followed by the development of male physical characteristics and muscle mass, structure, and function, as well as android adipose distribution and function Loss of lean body and muscle mass was reported to correlate with androgen levels in hypogonadal men Thus, it is possible that women with PCOS may develop male characteristics of muscle mass. Data on muscle size in women with PCOS are limited.
In the present study, we measured muscle mass in women with PCOS to investigate the relation between serum androgen levels and muscle size.
Materials and Methods
Fifty-four consecutive reproductive-aged, amenorrheic women with PCOS were recruited at the Infertility and Endocrinology Clinic, Kagoshima University Hospital, between January 1997 and June 1998. Exclusion criteria were excess alcohol consumption (n = 2), cigarette smoking (n = 1), previous or current oral contraceptive use (n = 2), and endurance physical training (n = 1). The remaining subjects were 48 women with PCOS 20–38 years old (mean ± standard deviation 28.0 ± 6.2). None of the subjects were taking medications likely to affect muscle size or body-fat distribution. All subjects had progestin-induced withdrawal bleeding (daily dydrogesterone 10 mg orally for 5 days) and were evaluated without regard to the menstrual cycle. Criteria for PCOS were chronic oligomenorrhea (six or fewer menses per year) or amenorrhea, elevated serum levels of LH with normal FSH and LH/FSH of at least 1.5, and polycystic appearance of the ovaries on ultrasound, defined by ten or more follicles 2–8 mm in diameter with a tendency toward peripheral distribution and bright echodense stroma.7 Each subject had a normal prolactin level and none showed evidence of androgen-secreting neoplasms, pituitary adenomas, homozygous adrenal hyperplasia, acromegaly, or Gushing syndrome.
Baseline characteristics included age, height, weight, and hirsutism status. Subjects with Ferriman-Gallwey scores exceeding 10 were defined as hirsute.8 Total-body lean mass was measured by whole-body scanning with dual-energy x-ray absorptiometry (QDR-2000; Hologic Co., Waltham, MA), and the lean mass index (total-body lean mass/height2, kg/m2) was calculated. Trunk-leg fat mass ratio (trunk/leg fat) was also assessed by dual-energy x-ray absorptiometry. Serum testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione levels were measured by commercially available radioimmunoassays (RIAs) with the DPC Total Testosterone Kit (Japan DPC Co., Chiba, Japan), the DPC DHEAS Kit Japan DPC Co.), and the Daiichi A Kit (Daiichi Radioisotope Co. Ltd., Tokyo, Japan), respectively. The intra-assay and interassay coefficients of variation for these RIAs were 3–5% and 8–10%, respectively. Subjects were divided arbitrarily into two groups of 24 each, according to a lean mass index above or below 14 kg/m2. Lean mass index was correlated with age, height, trunk/leg fat, and serum androgen levels.
Default software readings divided the body measurements into areas corresponding to the arms, trunk, and legs. The trunk region was delineated by an upper horizontal border below the chin, vertical borders lateral to the ribs, and a lower border formed by oblique lines through the hip joints. The leg region was defined as tissue below the oblique lines through the hip joints. The precision of these measurements was determined by five repeated measurements on six volunteers over 8 weeks; the results showed coefficients of variation less than 4%. All recordings were made by the same investigator, who was masked to the study.
Group comparisons were made using two-tailed Student t tests for continuous variables and χ2 test for categoric variables. The correlation of lean mass index with age, height, and androgen levels was determined by Pearson correlation coefficient. Correlation of lean mass index with hirsutism status was determined by univariate regression analysis in which the dependent variable was lean mass index. The independent variable was hirsutism status, which was a nominal variable, so we registered nonhirsute women as 1 and hirsute women as 2. Confidence intervals were calculated to evaluate the strength of correlation. P < .05 was considered statistically significant.
Informed consent was obtained from each subject, and the study was conducted in accordance with institutional guidelines and the Declaration of Helsinki.
Table 1 presents the baseline characteristics and serum androgen levels. The incidence of hirsutism, trunk/leg fat, and serum testosterone, androstenedione, and DHEAS levels were significantly higher in women with a lean mass index of at least 14 kg/m2. The total weight was greater in women with a higher lean mass index because a major proportion of weight includes lean mass. Age and height did not differ between the groups.
Table 2 presents the correlation coefficients between lean mass index and various variables. Trunk/leg fat and serum testosterone and androstenedione levels correlated positively with lean mass index. Hirsutism was also correlated with lean mass index on univariate regression analysis (standardized regression coefficient = .49; P < .05). Age and height were not correlated with lean mass index in the present series.
It is well known that androgens and anabolic steroids have been used to increase muscle size and strength.9 Because PCOS is characterized by obesity and hyperandrogenism, it is plausible that women with PCOS may have greater muscle size compared with controls. Anthropometric characteristics including excess body-fat mass, percentage of body fat, and androgenic body-fat distribution have been well documented in PCOS.10,11 However, only limited information is available about whether women with PCOS have androgenic muscularity. A possible reason for this may be the difficulty in assessing regional or total muscle mass. Little attention has been focused on muscle size in women with PCOS. Recent technologic advances in dual-energy x-ray absorptiometry equipment have made the precise assessment of regional fat, lean mass, and bone mass easier.12
Lean mass measured by dual-energy x-ray absorptiometry equipment generally includes muscle size. Loss of lean body and muscle mass correlates with serum androgen levels in hypogonadal men,6 whereas testosterone administration increases muscle size.13,14 Hirsutism and upper body-fat distribution are the consequence of higher serum androgen levels,10,15,16 and androstenedione is known to increase muscle size and strength. Thus, in women with PCOS, higher testosterone and androstenedione levels are important determinants of greater muscle size. This relation was independent of height because lean mass index is an indicator of lean mass amount per meter squared. A MEDLINE search of the English literature from 1966 to 1999 using search terms including PCOS and muscle size did not identify any previous studies.
We could not find any significant correlation between serum DHEAS levels and muscle size. This hormone is chemically classified as an androgen, serves as a precursor for other androgens,17 and has shown androgenic and estrogenic activity in humans.18 There are reports that androgenic body-fat distribution is associated with higher levels of DHEAS in premenopausal women,16,19 so it appears to have the potential to affect muscle size indirectly. Further extensive study is needed to elucidate the relation of DHEAS to muscle size.
Polycystic ovary syndrome is also characterized by hyperinsulinemia and a reduction of basal and stimulated growth hormone (GH) secretion.20 The effects of these hormones on muscle size and strength may be important, but we did not measure these hormone levels, so we cannot address the effect they may have on muscle size. Although PCOS is associated with muscular insulin resistance, there are reports that fasting insulin levels did not show any correlation with measurement of lean body mass.21 There is a report that GH administration increased lean tissue and muscle mass in adults with human GH deficiency22; however, the GH response to GH-releasing hormone is blunted in women with PCOS.20,23 To date, muscle size in women with PCOS cannot be explained by hyperinsulinemia or lower GH levels.
Our positive correlation between trunk/leg fat and lean mass index in women with PCOS suggests that greater muscle size is associated with androgenic fat distribution. It is likely that hyperandrogenism increases muscle size and induces upper-body adiposity. This conclusion agrees with the report by Krotkiewski and Bjorntorp,24 who found that obese women with androgenic fat distribution had male characteristics of muscle mass. Their study did not include women with PCOS but did include regularly menstruating women, so the association of androgenic muscularity with androgenic fat distribution was not specific to PCOS, but common to women with upper body-fat distribution and hyperandrogenism.
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