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Endocrine Care |
Johns Hopkins University School of Medicine (A.S.D., T.N.), Baltimore, Maryland 21287; and Solvay Pharmaceuticals, Inc. (C.P., C.P.R.), Marietta, Georgia 30062
Address all correspondence and requests for reprints to: Adrian Sandra Dobs, M.D., M.H.S., The Johns Hopkins Hospital, 1830 Monument Street, Baltimore, Maryland 21287. E-mail: . adobs{at}jhu.edu
Abstract
Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion. Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms. However, estrogen-androgen (E/A) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass.
The objective of this 16-wk, double-blind, randomized, parallel group clinical trial was to compare esterified estrogen plus methyltestosterone (1.25 mg estrogen + 2.5 mg methyltestosterone/d; E/A group) vs. esterified estrogen alone (1.25 mg/d; E group) on body composition. Forty postmenopausal women (mean age, 57 yr) participated.
Compared with estrogen treatment alone, women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts (P < 0.05). After E/A treatment, there were statistically significant increases in lean body mass by 1.232 kg [0.181 ± 0.004, 0.81 ± 0.057, and 0.24 ± 0.009 kg in the upper body (P = 0.021), trunk (P = 0.001), and lower body (P = 0.047), respectively]. In the E group, the increase was 0.31 ± 0.004, 0.021 ± 0.03, and 0.056 ± 0.05 kg in the upper body, trunk, and lower body, respectively. In the E/A group, body fat was reduced by 0.90 kg (P = 0.18 for the trunk only), and percentage body fat declined by 7.4% (P 
0.05 for all body parts). Lower body strength increased by 23.1 kg (51 lb) in the E/A group vs. only 11 kg (24.25 lb) in the E group (P = 0.002 between groups). A statistically significant increase in weight (2.7 ± 5.1 vs. 0.1 ± 4.6 lb; P < 0.05) was observed in the E/A group compared with the E group. When subjects were given self-reporting questionnaires, more improvement was noted in sexual functioning and quality of life in the E/A group when compared with patients receiving E alone. There were no noteworthy side effects.
In conclusion, E/A replacement therapy can improve body composition, lower-body muscle strength, quality of life, and sexual functioning in postmenopausal women.
MENOPAUSE HAS BEEN associated with loss of skeletal mass, loss of lean body mass, and increase in fat (abdominal, visceral adipose tissue) due to aging and declining ovarian hormone secretion (1, 2). The more time that passes after menopause, the greater the increase in weight, body mass index (BMI), and total and percentage body fat (3). During the first 3 yr after menopause, the loss of lean mass is as high as 3.78% (1). These changes in body composition can increase the risk of developing serious long-term health problems, especially osteoporosis and cardiovascular disease (CVD). One study concluded that lean tissue mass is closely related to bone mineral mass and that changes in bone mineral density are correlated to changes in fat tissue mass in healthy women (4). Additionally, increased abdominal fat has been linked to increased cardiovascular risk and insulin resistance (5).
Hormone replacement therapy (HRT), traditionally estrogen alone or estrogen-progestin (used for prevention of endometrial hyperplasia in women with an intact uterus), has been used primarily to alleviate vasomotor symptoms associated with menopause. HRT also provides protective effects on lipids, bone, and cognitive function (6, 7, 8, 9). A 2-yr trial by Hassager et al. (10) showed that HRT prevents the age-related increased fat observed after menopause. Other researchers discovered that women on a regimen of HRT developed significantly lower BMI and percentage of body fat when compared with nonusers (11) and concluded that HRT seemed to be associated with a reduction in postmenopausal weight and fat mass gains (12). A review of cross-sectional studies revealed that HRT reduced central fat accumulation when compared with control or placebo-treated women (5). However, Aloia et al. (13) found that HRT did not prevent increases in body fat in their study. Other studies dispute the notion that the HRT has a preventive effect on lean mass loss (14, 15, 16).
Not only do estrogen and progesterone levels decline after menopause, but androgen production also decreases significantly after ovarian contribution ceases. For women who have undergone surgical hysterectomy with oophorectomy, androgen levels rapidly decrease within 24–48 h after surgery (17, 18). As a result, androgen therapy was used as early as 1936 for treatment of menopausal symptoms (19, 20). Today, E/A therapy offers relief of vasomotor symptoms in postmenopausal women nonrespondent to E alone (21). Studies have demonstrated that E/A therapy increases well-being while providing beneficial effects on bone, lipids, sexual functioning, and quality of life (22, 23, 24, 25, 26). Earlier studies showed increases in lean mass and decreases in fat mass with different androgen therapies in postmenopausal women (27, 28). More recently, a clinical study conducted with androgen therapy in conjunction with diet and exercise demonstrated efficacy in reducing abdominal fat and weight in postmenopausal women with unexplained weight gain (29). A randomized, controlled trial studying the effects of various HRT regimens on body composition in postmenopausal women noted that tibolone (androgenic, estrogenic, progestogenic steroid) increased total lean body mass and decreased fat mass in postmenopausal women (16). Transdermal androgen treatment has been used to increase muscle mass and strength in women with HIV who are experiencing weight loss (30). In addition, androgen therapy has been shown to be effective in increasing muscle tissue in hypogonadal men (31).
This study investigated the effects of E/A therapy vs. E alone on fat mass, muscle mass, and muscle strength in postmenopausal women. Secondary objectives were to assess changes in sexual function, quality of life, and cardiovascular risk factors.
Subjects and Methods
Design
This single-center, double-blind, randomized parallel group trial enrolled 40 women who were either surgically or naturally menopausal. Thirty-seven women completed the study and were used in the final analysis (Fig. 1
). Patients were recruited from Johns Hopkins Hospital and associated institutions. Natural menopause was defined by a serum FSH level greater than 30 IU/liter or 6 months amenorrhea in patients over 55 yr of age before hormone therapy; surgical menopause was documented by chart review. Patients were required to have been on estrogen replacement therapy for at least 3 months before screening to remove confounding hypoestrogenic symptoms. Interestingly, all patients in this study were on prior estrogen therapy for more than 1 yr. Although the majority of our patients were on equivalent doses of oral estrogens, four patients were on prior transdermal estrogen applications, and one patient had been treated with im estrogen. None of the patients became symptomatic during the 16-wk study. All participants signed an informed consent approved by the Johns Hopkins Joint Committee on Clinical Investigation. Safety was assessed by spontaneously reported adverse events and a laboratory battery that included hematology, urinalysis, biochemistry, lipids, and thrombotic profile. A physical examination was conducted at baseline and at study termination; blood pressure and body weights were assessed periodically during the study. A Papanicolaou smear and mammogram were performed at screening if these tests had not been performed and found to be normal within 8 months before the study. Patients were excluded based on the following criteria: uncontrolled hypertension or hyperlipidemia, medication known to affect lipids, poorly controlled diabetes mellitus (HbA1C > 10%), unstable angina or congestive heart failure, myocardial infarction within 3 months of study, preexisting liver disease [aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >2 times the upper normal laboratory range and/or bilirubin >2.0 mg/dl (> 34.2 µmol/liter)], renal impairment [serum creatinine >2.0 mg/dl (>152.52 µmol/liter)], hepatic adenoma, history of breast or uterine cancer, gall bladder disease, or history of thromboembolic events.
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Outcome measures
Patients were assessed at weeks 0 (baseline), 4, 10, and 16 of the study. The baseline and 16-wk study results are primarily presented in this paper. The following methods were used to measure body composition.
Dual energy x-ray bone densitometry (DEXA). DEXA, a fan beam scanning technology, was used to obtain bone density measurements of the spine, hip, and forearm as well as fat mass, percentage fat tissue, and lean body mass of the trunk, legs, and arms. The Hologic 4500 A with specially designed software was used (Hologic Body Composition Analysis) (32, 33). DEXA measurements were performed by a certified technician.
Anthropometry. Anthropometric measurements included body weight, skinfold, hip, and waist measurements. The sc fat layer was estimated by averaging skinfold thickness on two sites on the left upper arm over the triceps using a caliper. BMI was calculated by dividing the body weight by height. Bioelectrical Impedance Analysis is a simple, noninvasive technique that uses electrical conductivity to estimate fat-free mass; muscle holds the majority of water in the body, so the more muscle, the better the conduction. The error of bioelectrical impedance is similar to that for the skinfold test. A low voltage is passed through the body to determine body fat. The slower the signal, the more fat is present. The signal travels quickly through muscle, which is made up of 70% water, and water conducts electricity. Fat is only 5–13% water, so it slows down the signal (34, 35).
Strength testing
Muscle strength was assessed using the one-repetitive maximum technique in separate leg and arm bench press exercises. This standardized procedure assesses the maximal force-generating capacity of the muscles. The patient warms up doing one or two sets of 10 repetitions at a low weight. Then, the patient lifts each weight level one time. The weight is increased until the patient is unable to lift it. This is determined to be the maximum weight. The procedure is repeated, and the higher weight of the two values is used. The patients were tested on Nautilus weight-lifting equipment for all studies.
Laboratory assessments
Hormone profile.
All blood samples were obtained between 0700 and 1000 h, before the oral administration of drug. A hormone profile of FSH, LH, total estrogen, and E2 was analyzed in bulk using standard kit RIA techniques (performed by Quest Diagnostics, Inc.-Nichols Institute Diagnostics, San Juan Capistrano, CA). A T profile was analyzed separately (performed by Endocrine Sciences, Inc., Calabasas Hills, CA). Total T and free T were measured using RIA, whereas SHBG and percentage free T were analyzed using immunoradiometric assay and dialysis techniques. The sensitivity for the total T assay was 2 ng/ml. Total T is purified by using a celite column and then quantitated by RIA (coefficient of variance, 13%). There was no cross-reactivity with methyltestosterone in this assay. The free T was calculated after incubation of the serum with 3H-testosterone for 2 h and then separated from the SHBG fraction by ice-cold supersaturated ammonium sulfate. Upon equilibrium, liquid scintillation was used to determine radioactivity in the serum and buffer. Free T was calculated by taking into account the binding by SHBG and albumin (5.5%). The bioavailable T was then calculated using the percentage bioavailable (unprecipitated dpm/total dpm) and the total T value. Although attempts were made to obtain serum samples before oral administration of drugs, this was not always possible. The coefficients of variability for the assays were: total T, 13%; E2, 15% (goat antirabbit 
globulin and PEG); PRL, 15%; FSH, 5%; and LH, 4% (immunochemiluminometric assay).
Lipid profile. Twelve-hour fasting serum samples were collected to measure cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels. Samples were analyzed at a central laboratory by in vitro diagnostic kits (Quest Diagnostics, Inc., Baltimore, MD). LDL values were based on calculated total cholesterol, triglyceride, and HDL results.
Statistical analysis
A sample size of 36 randomized patients (18 per treatment group) was calculated on the basis of percentage change in lean body mass to provide 0.8 power at a 0.05 significance level to detect differences between groups. Originally, we had calculated a 28% dropout rate, thus requiring us to enroll 50 patients to assure appropriate power for the study. However, due to a reassuringly low dropout rate (three patients), we enrolled and randomized 40 women and still met our power calculations. All data were entered into Paradox, a data entry program, and analyzed in SAS (SAS Institute, Inc., Chicago, IL). Because there were only three dropouts, all analyses were performed on completed subjects.
Fisher’s exact test was used for comparison of the distributions of the type of menopause. The t test was used for comparison of the age distribution. For each part of the body, the change in body composition measures was analyzed with the one-way ANOVA model. The body composition measures were also analyzed with a multivariate model to evaluate the difference in treatment effect on the body as a whole. For all other variables, the change from baseline was analyzed with the analysis of covariance (ANCOVA) model with a post hoc Wilcoxin test. Statistical significance was defined as a P value no greater than 0.05.
Descriptive statistics for secondary measures [Brief Index of Sexual Functioning for Women (BISF-W), Sabbatsberg Revised Sexual Self-Rating Scale (SRS), and Sexual Interest Questionnaire (SIQ)] were tabulated. The composite sexual function scores for BISF-W, SRS, and SIQ were analyzed to evaluate treatment effect on sexual function using a t test to compare baseline distributions of the continuous variables in the two treatment groups. A P value less than 0.05 between any of the subjective variables that were tabulated was considered significant.
The BISF-W is a 22-item, validated self-report instrument for the assessment of current levels of female sexual functioning and satisfaction. It was designed to assess both quantitative and qualitative aspects of women’s sexual experience (36). The SRS is a validated, self-reported questionnaire designed to assess female sexual function (37). The SIQ is a one-dimensional self-report designed to evaluate 10 items at baseline and monthly intervals during drug administration. The items are rated on a 7-point scale, with 70 points being the highest rating one can score (38). For the Quality of Life at Menopause Scale (QUALMS), descriptive statistics for seven domains (somatic, depression, anxiety, cognitive difficulties, sexual functioning, vasomotor/sleep problems, and well-being) were tabulated on a six-point scale for each treatment group (39) and then analyzed.
Results
Thirty-seven of the 40 enrolled patients completed the study (19 in the E group and 18 in the E/A group). Three patients terminated early due to adverse events (two in the E/A group and one in the E group) (Fig. 1
).
Demographics
Baseline demographic information is presented in Table 1. There were no statistically significant differences between the E and E/A groups in any parameter. Of the 40 women enrolled in the study, 85% were Caucasian, with a mean age of 57 yr and mean weight of 157 lb. The mean time since menopause was 10 yr, and all women had received HRT for longer than 1 yr.
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E/A treatment when compared with E alone significantly increased lean body mass in the arms, legs, and trunk (Fig. 2). Body fat percentage decreased significantly from baseline in the arms, legs, and trunk in the E/A group but not the E alone group (Fig. 3). When changes in arms, legs, and trunk in each patient were analyzed simultaneously, the difference between treatments was significant for lean body mass (P = 0.007) and percentage of fat tissue (P = 0.002), but not significant for fat tissue (P = 0.077) (Table 2).
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Anthropometric measurements
Women randomized to E/A gained 2.7 ± 5.1 vs. 0.1 ± 4.6 lb in the E group (P < 0.05 between groups). Similarly, the former group decreased their skinfold thickness by 4.3 ± 7.4 cm vs. a reduction of 0.6 ± 3.5 cm in the E group (P < 0.05 between groups). There was no change in the hip or waist circumference. No statistical significance was noted with any subanalysis, including age, baseline weight, BMI, or type of menopause.
Strength testing
In patients in the E/A group, the upper body press at baseline was 20 ± 6.8 kg (43 ± 14.9 lb), which increased to 23 ± 7.4 kg (50 ± 16.4 lb) (P < 0.036); whereas leg press increased from 107 ± 33.7 kg (235 ± 74.2 lb) to 130 ± 28.6 kg (286 ± 62.8 lb) (P < 0.0024). In patients on E therapy, upper body press and lower body leg press increased by 1 kg (2 lb) and 11 kg (24 lb), respectively (P > 0.1). When comparisons were made between groups, there was a significant increase in lower body strength only for women on androgens.
Hormone profile
After 16 wk of treatment, the increase in E2 was similar in the two treatment groups. The E/A group had a significantly greater increase in percentage free T than the E group (P = 0.010), but the change in free T or total T did not differ significantly between the two groups (P = 0.092 and P = 0.085, respectively). The reductions in LH and SHBG were significantly greater in the E/A group than in the E group (P = 0.019 and P = 0.012, respectively), therefore suggesting an androgen effect.
Neither baseline BMI nor weight significantly influenced hormonal changes during the study; nor did age, except for E2 and SHBG (P = 0.068 and P = 0.079, respectively, for age by treatment interaction). Younger patients exhibited a greater SHBG increase in the E group than the E/A group.
Patients with surgical menopause experienced greater E2 change than did those with natural menopause while on E/A treatment (P = 0.030), but no significant difference in E2 change was noted between surgical menopause and natural menopause for E treatment. No significant difference in FSH change was noted between type of menopause in either treatment group.
Lipid profile
After 16 wk of treatment, significant decreases in total cholesterol, HDL, and triglycerides occurred in the E/A group; LDL values were virtually unchanged. The E treatment group demonstrated the opposite effect on lipids, with a significant decrease in LDL and no meaningful change in the other lipid parameters.
Secondary outcome data
Sexual functioning and quality of life. Our sample size was not powered, nor was our entry criteria designed to assess sexual dysfunction parameters. However, we did notice significant results. The BISF-W, SRS, and SIQ were used to evaluate sexual functioning. In the E/A group, BISF-W mean increases at each visit were statistically significant for frequency/psychosexual (P = 0.05) and pleasure/orgasm (P = 0.041) domains. The mean composite BISF-W score increased in the E/A group, whereas the mean score in the E group decreased. Although it appeared that the two treatment groups were not well balanced at baseline (the E group seemed to have a healthier sexual function at baseline than the E/A group), the E/A group showed significant improvement in sexual function compared with the E group.
The SRS total score in the E/A group improved significantly at each visit, whereas scores in the E group did not change significantly. The SIQ score for the E/A group also increased significantly for interest in sex at weeks 10 (P = 0.031) and 16 (P = 0.014) when compared with before menopause. The E group showed no significant change from baseline.
The six-point QUALMS questionnaire was administered to patients to assess their quality of life for seven domains (somatic, depression, anxiety, cognitive difficulties, sexual functioning, vasomotor/sleep problems, and well-being). Overall, both groups showed improvements from baseline. The E/A group showed significant improvements from baseline in somatic symptoms (week 4, P = 0.004; week 10, P = 0.021), sexual functioning and vasomotor symptoms (week 4, P = 0.024; week 10, P = 0.003; week 16, P = 0.073). The E group showed improvements from baseline in well-being (week 4, P = 0.003; week 16, P = 0.049) and cognitive difficulties (week 10, P = 0.054).
Safety data.
Three patients withdrew because of to the following adverse events: 1) bloating and weight gain (E/A group), 2) migraine (E/A group), and 3) insomnia, swollen breasts, and headaches (E group). Two patients in the E/A group experienced mild hirsutism. There were no significant changes in liver function tests in either group, except for a 3-IU reduction in serum -glutamyl transpeptidase in the E group, a finding with little clinical significance (data not shown).
Discussion
Changes in body composition with age are well documented; both men and women have an increase in fat and decrease in lean body mass as they age (40). Although the relationship of body composition to morbidity and mortality is still being defined, it is recognized as an important prognostic factor in several disease states, such as HIV (41), CVD (42, 43), and osteoporosis (44). Similarly, improved functional status has also been associated with preservation of lean body mass. Excess body fat, particularly increased abdominal obesity, is a strong cardiovascular risk factor, more than total fat or weight alone (42, 43). Lean mass is one of the primary determinants of bone mineral density through increased mechanical stress on the bone (44). Androgen therapy in postmenopausal osteoporotic women results in a leaner body mass and decreased fat tissue, although the body returns to its initial composition after cessation of therapy (27). Our data, which show an increase in lean body mass and a decrease in percentage fat tissue in the arms, legs, and trunk after 4 months of treatment with combined E/A therapy, may have important significance in a subset of women with or at risk for certain diseases.
The E/A group experienced an increase in weight, whereas the E group displayed a decrease in weight. The increase in lean body mass in the E/A group, coupled with the decrease in fat mass, may explain the weight gain for this group because muscle weighs more than fat. In addition, increased lean body mass and decreased fat mass in the upper body, especially the right arm, was noted during the course of this pilot study. This finding was unexpected, it does not correlate to right- or left-handedness, and we are unable to offer an explanation for this trend. The beneficial effects on body composition were noted without control of diet or exercise regimen in either treatment group. The DEXA scan served as the primary outcome measure to document body composition because it has superseded hydrodensitometry as the standard to estimate percentage body fat (45). Measurements using the DEXA scan are only minimally affected by hydration status (46) and thus did not affect our results.
The mechanism of increased muscle mass from androgen treatment is not clear, although thymidine incorporation studies do demonstrate increased protein synthesis (47).
Although this study has a small sample size, we were able to show statistically significant increases in both upper and lower body strength. This is similar to observations noted by other investigators, especially in conjunction with an exercise intervention such as the one used in this study (48). We did not measure functional activity in this study, although this information might prove useful in a frail, postmenopausal patient. Because this study used healthy postmenopausal women, it is unlikely that a significant change in functional status would have been demonstrated. Further studies need to be performed to examine the functional improvement in an older or frailer patient population to elucidate this likely benefit of E/A therapy.
Historically, the higher doses of injectable androgens prescribed to women often resulted in virilizing effects such as hirsuitism and acne. The oral E/A treatment used in this study had a significantly lower dose of methyltestosterone than was used in early studies (19). To date, no liver toxicity has been reported with this treatment, and the drug causes few side effects (49, 50, 51). Although this dosage of estrogen replacement may not be necessary for cardiovascular and bone effects, we chose this formulation of estrogen-androgen for the beneficial effects of the higher dose of methyltestosterone. In addition, we chose to deliver a progestin after the study in order not to confound our primary outcome, i.e. determining what are the effects of androgens on body composition. However, in clinical practice progestins are usually administered together with estrogens. The small differences noted between natural vs. surgical menopause are likely not relevant with our small sample size.
The data also showed an interesting change in serum hormone levels. The 1.25-mg dose of estrogen resulted in an expected increase in serum total E2. The significantly greater decrease in SHBG in the E/A group translates into increased free T levels resulting from an increase in endogenous T and administration of methyltestosterone. E/A therapy in other studies, as well as our study, decreases SHBG, increases free T, and decreases total T (24). Free T values in our study, although increased in the E/A group, did not approach statistical significance. This may be accounted for by inability to control medication administration and blood sampling times; however, we maintain that the biological effect observed in the E/A treatment group, both by LH and SHBG suppression and the increase in lean body mass, is the significant bottom line. Some researchers have suggested that reduced SHBG levels are independently associated with abdominal fat distribution by causing an increase in free androgens at the tissue level that may play a role in the expansion of visceral fat (52). Conversely, in our study the E group, with higher levels of SHBG and lower levels of free T, experienced an increase in fat mass and decrease in lean body mass.
The Heart and Estrogen/Progestin Research Group findings (53) led many to question the cardioprotective benefits of HRT in women experiencing cardiovascular events; however, the data also showed that women on an HRT regimen for a minimum of 1 yr appear to receive cardioprotective benefits from this therapy. In our study, estrogen-androgen significantly decreased triglycerides and LDL but also decreased HDL below the recommended range of the National Cholesterol Education Program Guidelines (54). We believe this decrease may be associated with the higher dose of methyltestosterone used. It is known that CVD risk is associated with low HDL and high LDL. However, there has been growing evidence that hypertriglyceridemia is also an important risk factor for CVD (55, 56, 57). Additional long-term studies are needed to determine which laboratory parameters are the best predictors of CVD risk in postmenopausal women taking HRT, especially with androgen supplementation. The reduction in truncal fat by 4% in the E/A group may also have clinical importance toward prevention of CVD.
Studies with androgen treatment have shown increases in well-being and sexual functioning in postmenopausal women (25, 58). We noted an increase in well-being with both treatment groups as well as improvement in quality of life parameters. The E/A group had significant improvements in sexual functioning scores on all three scales, plus improvement in the sexual functioning domain of the QUALMS.
In this study, the patients were treated with E or E/A therapy alone for the duration of the 4-month study period. In women with an intact uterus, endometrial protection was provided by the addition of continuous or cyclical progestin. All patients in our study with an intact uterus were given 14 d of progestin after completion of the study. Routine practice provides monthly progestin in either a cyclical or continuous form, and it is not known how the addition of progestins would affect the results of this study. In addition, these beneficial effects occurred without liver toxicity or other notable side effects, although the long-term effects on the liver are not available from this short-term study.
In conclusion, we found that 4 months of E/A therapy, when compared with E-only therapy in healthy postmenopausal women, increased their total lean body mass and lower body muscle strength, reduced body fat, and improved quality of life and some parameters of sexual function.
Acknowledgments
We thank J. P. Hsu for providing the statistical analysis of the data and Lois J. Birkhimer and Susan Kuebler for their role in developing and editing the manuscript.
Footnotes
This research was partially supported by The Johns Hopkins University School of Medicine General Clinical Research Center, NIH/National Center for Research Resources Grant M01 RR00052. This research was also funded in part by Solvay Pharmaceuticals, Inc.
Portions of this manuscript were presented at the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000; the 81st Annual Meeting of The Endocrine Society, San Diego, California, 1999; and the 10th Annual Meeting of the North American Menopause Society, New York, New York, 1999.
Abbreviations: BISF-W, Brief Index of Sexual Functioning for Women; BMI, body mass index; CVD, cardiovascular disease; DEXA, dual energy x-ray bone densitometry; E/A, estrogen-androgen; HDL, high-density lipoprotein; HRT, hormone replacement therapy; LDL, low-density lipoprotein; QUALMS, Quality of Life at Menopause Scale; SIQ, Sexual Interest Questionnaire; SRS, Sabbatsberg Revised Sexual Self-Rating Scale.
Received October 3, 2000.
Accepted December 15, 2001.
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S. E. Chiuve, L. A. Martin, H. Campos, and F. M. Sacks Effect of the Combination of Methyltestosterone and Esterified Estrogens Compared with Esterified Estrogens Alone on Apolipoprotein CIII and Other Apolipoproteins in Very Low Density, Low Density, and High Density Lipoproteins in Surgically Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2207 - 2213. [Abstract] [Full Text] [PDF]
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C. E. Wood, J. M. Cline, M. S. Anthony, T. C. Register, and J. R. Kaplan Adrenocortical Effects of Oral Estrogens and Soy Isoflavones in Female Monkeys J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2319 - 2325. [Abstract] [Full Text] [PDF]
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J. E. Morley and H. M. Perry III Androgens and Women at the Menopause and Beyond J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M409 - 416. [Full Text] [PDF]
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A. M. Kenny, L. Dawson, A. Kleppinger, M. Iannuzzi-Sucich, and J. O. Judge Prevalence of Sarcopenia and Predictors of Skeletal Muscle Mass in Nonobese Women Who Are Long-Term Users of Estrogen-Replacement Therapy J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M436 - 440. [Abstract] [Full Text] [PDF]
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B. Z. Leder, K. M. LeBlanc, C. Longcope, H. Lee, D. H. Catlin, and J. S. Finkelstein Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5449 - 5454. [Abstract] [Full Text] [PDF]
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M. Iannuzzi-Sucich, K. M. Prestwood, and A. M. Kenny Prevalence of Sarcopenia and Predictors of Skeletal Muscle Mass in Healthy, Older Men and Women J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2002; 57(12): M772 - 777. [Abstract] [Full Text] [PDF]
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M. R. Blackman, J. D. Sorkin, T. Munzer, M. F. Bellantoni, J. Busby-Whitehead, T. E. Stevens, J. Jayme, K. G. O'Connor, C. Christmas, J. D. Tobin, et al. Growth Hormone and Sex Steroid Administration in Healthy Aged Women and Men: A Randomized Controlled Trial JAMA, November 13, 2002; 288(18): 2282 - 2292. [Abstract] [Full Text] [PDF]
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