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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
Address reprint requests to: Tsutomu Douchi, MD, Faculty of Medicine, Department of Obstetrics and Gynecology, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: Seventy-one amenorrheic and right-side dominant women with PCOS (mean age ± standard deviation 28.1 ± 6.7 years) were enrolled. Baseline characteristics included age, height, weight, and body mass index (BMI). Regional BMD and lean mass were measured by whole-body scanning with dual-energy x-ray absorptiometry. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were measured by radioimmunoassay. Correlations between regional BMD and variables were investigated using a Pearson correlation test and multiple regression analysis.
RESULTS: Serum testosterone levels correlated significantly with lean mass of the left arm, right arm, trunk, left leg, and right leg (r = .34, P < .05 to r = .50, P < .01). Regional lean mass correlated significantly with respective regional BMD (r = .30, P < .05 to r = .68, P < .001). These relationships remained significant after adjusting for age, height, and weight. Serum testosterone levels were not correlated with BMD of the bilateral arms and lumbar spine. Although serum testosterone levels correlated with leg BMD (r = .34, P < .05 to r = .45, P < .01), significance did not persist after adjusting for respective regional lean mass.
CONCLUSION: Testosterone influences regional BMD through increasing regional muscle mass in women with polycystic ovary syndrome.
Androgens have many important physiologic actions, including effects on muscle mass, bone, central nervous system, prostate, bone marrow, and sexual function.1 Hyperandrogenism is one of the important characteristics of polycystic ovary syndrome (PCOS). The atypical hormonal milieu in PCOS allows important insights into the effect of androgen excess on bone mineral density (BMD),2–4 body fat distribution,5 and body composition6 in women. Recently, Good et al7 found that slender women with PCOS had higher arm BMD compared with controls. However, underlying mechanisms of this phenomenon remain to be clarified. It is well known that androgens have been used as muscle-strengthening agents. Muscle mass influences BMD through mechanical action.8–10 Regional muscle mass contributes to regional BMD in premenopausal women.11 The present study investigated whether the relationship of androgens to BMD is mediated by muscle in PCOS.
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MATERIALS AND METHODS |
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Criteria for PCOS were as follows: the presence of chronic oligomenorrhea (six or fewer menses per year) or amenorrhea, elevated serum levels of LH with normal FSH and LH:FSH ration at least 1.5, and polycystic ovarian ultrasound appearance defined by the presence of ten or more follicles 2–8 mm in diameter with a tendency for peripheral distribution and bright echodense stroma.12 Each woman had normal prolactin levels.
Baseline characteristics included age, height, weight, and body mass index (BMI). Body mass index was calculated as weight (kg) divided by height squared (m2).
Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were measured by commercially available radioimmunoasays (Total Testosterone Kit [Diagnostic Product Corp., Los Angeles, CA], the DHEAS Kit [Diagnostic Product Corp.], and the A Kit [Daiichi Radiisotope Co., Ltd., Tokyo, Japan], respectively). The intra-assay and interassay coefficients of variation for these radioimmunoassays were 3–5% and 8–10%, respectively.
Regional lean mass, including arms, trunk, and legs, were assessed by whole-body scanning with dual-energy x-ray absorptiometry (QDR 2,000/W, Hologic Inc., MA). Lean mass measurement does not include bone mineral content. Bone mineral density of the arms, lumbar spine (L2–4), and legs were measured by whole-body scanning with dual-energy x-ray absorptiometry. The precision of regional lean mass and BMD was determined by repeated measurements in six volunteers over 8 weeks. Precision of these measurements was indicated by coefficients of variation that were all less than 4%.
Dual-energy x-ray absorptiometry measurements were made between 9:00 AM and 12:00 PM with a total body scanner, and results were evaluated by the same examiner. This equipment uses switched, pulsed, stable dual-energy radiation with voltages of 70 and 140 kV. The machine performs serial transverse scans from head to toe at 1.2-cm intervals, providing a pixel size of 1.9 mm x 1.2 mm. The radiation dose is 0.05–0.15 µGy. Default software readings divided body measurements into areas corresponding to arm, 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 the oblique lines passing through the hip joints. The leg region was defined as tissue below the oblique line passing through the hip joint. All recordings were done by the same experienced investigator. The examiner was masked to the study status.
All variables were distributed normally and met criteria for normality by basic descriptive statistics, inspection of the histogram, and a normality plot. Differences in lean mass and BMD between dominant and nondominant extremities were investigated using paired t tests. Correlations between the variables were investigated using a Pearson correlation test. Confidence intervals for correlations and prediction intervals were calculated to evaluate accuracy. Significant independent determinants of regional BMD were investigated using multiple regression analysis. On multiple regression analyses, dependent variables were regional BMDs. Independent variables were age, height, weight, respective regional lean mass, or serum androgen levels, as appropriate. On multiple regression analysis, the strength of correlation was shown using standardized regression coefficient, which is a coefficient similar to Pearson correlation coefficient. P < .05 was considered significant.
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RESULTS |
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presents the demographic data, serum androgen levels, regional BMD, and regional lean mass. Bone mineral density and lean mass in the right arm were significantly greater than those in the left arm (P < .001). Lean mass was significantly greater in the right leg than in the left leg (P < .05), although BMD did not differ between the bilateral legs.
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presents the outcome of Pearson correlation tests. Serum testosterone levels correlated positively with lean mass in each region (r = .34, P < .05 to r = .50, P < .01). However, serum androstenedione and DHEAS levels did not correlate with lean mass or BMD in any segmental region (r < .25, P > .1). Regional lean mass also correlated significantly with respective regional BMD (r = .30, P < .05 to r = .68, P < .001). These relationships remained significant after adjusting for age, height, and weight (Table 3). Serum testosterone levels did not correlate with BMD of the bilateral arms and lumbar spine. Although serum testosterone levels correlated positively with bilateral leg BMD (r = .34, P < .05 and r = .45, P < .01), statistical significance did not persist after adjusting for respective regional lean mass (Table 3).
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DISCUSSION |
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ethinyltestosterone, induces striking changes in body composition (ie, significant increase in muscle mass and decrease in body fat mass) in reproductive-aged women with endometriosis.16 In women with PCOS, testosterone also is an important determinant of regional muscle mass. The effects of androgens on BMD have been explained by direct (androgenic) or indirect (estrogenic) effects.17–23 However, little attention has been paid to the effect of androgen-related muscle size or strength on BMD. In the present study, we found that regional muscle size correlated positively with regional BMD, irrespective of age, height, and weight. This finding suggests that regional muscle mass is the important determinant of regional BMD. Our finding of no significant correlation between DHEAS and regional BMD agrees with that of Good et al.7 Although we found significant correlations between testosterone and regional BMD in the leg, those relationships depended on regional lean mass, according to multiple regression analysis. This finding disagrees with that of Good et al,7 indicating that testosterone levels correlated closely with arm BMD across women with PCOS and controls (r = .62, P < .01). Their study included more androgenic women (serum testosterone levels, 73.7 ± 21.3 ng/dL) than did ours (63.5 ± 20.4 ng/dL). Higher arm BMD in women with PCOS compared with controls leads us to hypothesize that localized stimulatory effects of testosterone affect bone. These effects might be mechanical or otherwise. However, their study included a small sample size (n = 22), and further study is needed.
A longitudinal study by Lovejoy et al24 found that women treated with a weak androgen gained lean body mass despite overall weight loss, and that result was attributable mainly to a significant increase in the midthigh muscle area. It appears that androgen enhances muscle size in all the extremities more than that in the trunk because of greater daily physical activity in the arm. Thus, Good et al7 speculated that testosterone-mediated increases in arm muscle size were responsible for the higher arm BMD in women with PCOS. In fact, in their study, there was a trend toward decreased total and regional percentage of body fat (ie, increase in percentage of total and regional lean mass) in the women with PCOS compared with controls.
Leg BMD did not differ between the women with PCOS and controls in the study by Good et al.7 Unfortunately, our study was not a controlled study, so we can not address this phenomenon directly. Bone mineral density on the horizontal axis, such as the arm, is not affected by weight-bearing effects but is influenced by non–weight-bearing effects. Conversely, BMD of the vertical axis is influenced by both weight-bearing and non–weight-bearing effects. Significant determinants of BMD definitely differ by segmental region. In the leg, body weight is another important determinant of BMD.11 As shown by the present study, weight is approximately six times greater than leg lean mass amount. The effect of leg muscle mass on respective leg BMD might be offset by the greater weight-bearing effects of higher body weight.
Based on these results, we conclude that testosterone influences regional BMD through increasing regional muscle mass in women with PCOS. However, it appears that this relationship is not specific to women with PCOS but is characteristic of androgenic women, because android anthropometric characteristics even in regular menstruating women proved to be associated with higher BMD.25
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Footnotes |
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Received December 11, 2000. Received in revised form April 17, 2001. Accepted April 26, 2001.
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REFERENCES |
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