Secondary Logo

Journal Logo

CLINICAL SCIENCE

Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial

Dolan Looby, Sara Ea; Collins, Merreditha; Lee, Hangb,c; Grinspoon, Stevena,c

Author Information
doi: 10.1097/QAD.0b013e3283299145
  • Free

Abstract

Introduction

Prior studies have demonstrated that androgen deficiency is prevalent among women with HIV [1–4] and associated with reduced lean body mass, functional status, and bone mineral density (BMD) in this population [1,3,5]. The effects of short-term testosterone have been reported in a limited number of studies of HIV-infected women [1,3,6]. However, little is known regarding the long-term effects of testosterone administration in this population.

An initial 12-week, dose-ranging, pilot study investigated the safety and efficacy of testosterone replacement and concluded that testosterone was well tolerated and associated with a trend toward improvement in weight and quality of life [3]. In a 6-month randomized, placebo-controlled study of 150 μg of testosterone twice weekly, a trend toward improvement in lean muscle mass was demonstrated [1]. A 24-week randomize, placebo-controlled study determined that a higher testosterone dose of 300 μg twice weekly was well tolerated but did not significantly affect body composition [6].

The purpose of the current study was to determine the effects of long-term testosterone administration, 300 μg twice weekly vs. placebo, over 18 months. Primary study endpoints included lean body mass and BMD. Quality of life parameters of depression, sexual function, and safety were investigated.

Methods

Recruitment and enrollment

Women were recruited from 2004 to 2006 via community and newspaper advertisements and provider referral. Eligibility was established based on age 18–55 years, BMI of 26 kg/m2 or less, HIV infection, relative reduction in androgen levels (free testosterone level <3.0 pg/ml, median of the normal range for women by equilibrium dialysis), creatinine less than 1.5 mg/dl, normal serum calcium, and follicle-stimulating hormone (FSH) less than 25 if oligomenorrheic. The specific age range was chosen to exclude women younger than 18 years in whom effects on growth might be seen and in women more than 55 years of age who were more likely to be postmenopusal. Women were excluded for any change in antiretroviral regimen or use of an anabolic agent, including testosterone, growth hormone, or other preparations within 3 months of study participation. Women were also excluded for current use of estrogen or any preparation known to affect BMD or bone turnover, including oral contraceptives, transdermal contraceptive patches, depo provera, and combined progesterone–estrogen injections or history of congestive heart failure, unstable angina, deep vein thrombosis, breast cancer, or sleep apnea. Pregnancy testing was performed at baseline and at each subsequent visit and women were excluded for a positive pregnancy test. Women were required to demonstrate understanding of appropriate barrier contraceptive methods, have a history of a tubal ligation, or hysterectomy prior to study entry, or all. Stable use of lipid-lowering and antidiabetic medications were permitted.

Protocol and randomization

This study was approved by the institutional review board at Massachusetts General Hospital (MGH) and Massachusetts Institute of Technology (MIT). All patients gave written and informed consent. Free testosterone, calcium, 25-hydroxyvitamin D level, urine pregnancy testing, medical history, including menstrual history, weight and BMD by dual-energy X-ray absorptiometry (DEXA), were obtained at the screen visit.

The primary care physician for each eligible patient was contacted prior to the baseline visit to confirm safety of study enrollment and provide details on the study procedures. Patients more than 40 years of age were required to have a mammogram performed within 1 year of study enrollment and provide a copy of these results prior to the baseline visit.

Eligible patients attended a baseline study visit in the morning following a 12-h fast. Fasting blood was drawn for testosterone, free testosterone, sex hormone-binding globulin (SHBG), estradiol, luteinizing hormone (LH), FSH, lipids, liver function tests, glucose, insulin, CD4 cell count, and viral load. Patients also underwent a standard oral glucose tolerance test. Patients provided a 4-day food record to determine caloric intake and a menstrual history. A history and physical examination were performed, and acne and degree of hirsutism were assessed. Patients underwent DEXA scanning for assessment of BMD and body composition and completed surveys evaluating mood and sexual function. All study patients were seen 1 month after the baseline visit for a safety visit, every 6 weeks for a urine pregnancy test, and every 3 months for blood work, urine pregnancy testing, history, and physical examination. Visits identical to the baseline visit occurred at 9 and 18 months. Compliance was assessed at each visit by count of returned patches. A supply of study medication and a menstrual diary were distributed to patients at each visit after confirmation of a negative pregnancy test and safety and compliance assessment. After the 18-month visit, all patients were offered open-label testosterone for an additional 12 months as a further incentive to enter the study and collect long-term safety data. Patients remain enrolled in this second open-label phase of the study, the results of which will be reported at a later date after all patients complete the study.

Patients were randomly assigned to receive either active testosterone transdermal delivery system (estimated delivery dose 300 μg/day, changed twice weekly; 8.4 mg patch; Procter and Gamble Pharmaceuticals, Mason, Ohio, USA), or an identical placebo patch. The dose was chosen on the basis of dose-ranging pilot studies suggesting that the 300 μg dose was well tolerated [3] and would be more effective than a 150 μg dose [1] in HIV-infected women. Study investigators and patients were blinded to drug assignment, and randomization was performed by the Research Pharmacy at the MGH. Randomization was stratified by BMD (lumbar T score < or ≥ −1.0 SD by DEXA at screen visit) using a permuted block algorithm with randomly generated numbers. Patients were instructed on proper patch application technique and were told to return all used and unused patches to the investigator at subsequent study visits for assessment of compliance. Patients applied their first patch upon completion of the baseline visit.

Laboratory assessment

Testosterone and immunologic assays

Free testosterone was measured by equilibrium dialysis (Esoterix, Calabasas Hills, California, USA, coefficient of variation 6.6–9.4%) with a normal range of 1.1–6.3 pg/ml for women. HIV RNA was quantified from 400 to 750 000 copies/ml (Roche Diagnostics, Indianapolis, Indiana, USA, processed by the Emory Center for AIDS Research, Atlanta, USA).

Nutritional assessment and body composition

Height, fasting weight, and BMI were determined [7]. Food records were analyzed using Nutrition Data System, version 2006. Total body lean mass and fat, in addition to BMD at the lumbar spine, total hip, and greater trochanter were measured using DEXA (Hologic Inc. 4500, Bedford, Massachusetts, USA). Precision for total body lean and fat mass is 3% and 1.5% for bone [1,5].

Mood state and sexual function

Mood and sexual function were evaluated by questionnaires completed by study patients. Depression was evaluated with the Beck's Depression Inventory (BDI) [8], and sexual function was assessed with the brief index of sexual function for women (BISF-W) [9]. Patients were instructed to answer all questions. The BISF-W consists of 22 items with seven domains, including thoughts and desires, arousal, frequency of sexual activity, receptivity/initiation, pleasure, relationship satisfaction, and problems affecting sexual function. Data from one patient who did not complete the BDI were excluded.

Safety

Patients were counseled on appropriate barrier contraception methods at each visit, and a urine pregnancy test was performed on all patients every 6 weeks. Patients who experienced increased hair growth (e.g. facial hair) could remain in the study on a lower dose of testosterone (one patch per week), but dose reductions were not necessary, and full dosing was continued throughout the study for all patients. Changes in menstrual status, missed periods, irregular bleeding or all were noted and reported back to the primary care physician if significant (see safety assessment). One woman in the placebo group discontinued because of irregular menstrual bleeding. A data and safety monitoring board met every 3 months to monitor the adverse events in the study.

Statistical analysis

Baseline comparisons between the two groups were analyzed using the Student's t test for continuous variables and chi-squared analyses for categorical variables. Summary statistics are presented as mean ± SEM for continuous outcomes and frequency (%) for categorical outcomes. A longitudinal linear mixed effects model was applied to evaluate the effect of 300 μg twice-weekly transdermal testosterone patch over 18 months in which the intercept and effect of time were random. Exploratory data analysis revealed that the response after 18 months was not different from the response at 9 months. Responses at 9 and 18 months were pooled as the posttreatment repeated measures. All data were included in the analysis, including 9-month data from the four patients who discontinued after the 9-month visit. For immune parameters, CD4 cell count and viral load, nonparametric comparisons were made by the Wilcoxon test between treatment groups at baseline, 9, and 18 months during the study. The study was powered at 80% to detect a significant treatment difference of 2.7 kg in lean body mass between randomization groups, with 25 randomized patients and a 15% assumed dropout rate, using a two-sided 5.0% significance level. Power calculations were based on the short-term study by Choi et al.[6], demonstrating a 2.3 kg SD for the change in lean body mass over 24 weeks in response to a similar dose of testosterone in HIV-infected women. Data were analyzed using JMP statistical software and SAS, version 9 (SAS Institute, Cary, North Carolina, USA).

Results

Recruitment and enrollment

Thirty-four women were screened for the study, and 25 were randomized (Fig. 1). Twenty-five women were randomized to receive testosterone (n = 13) or placebo (n = 12) and received study drug. Four women discontinued study participation after the 9-month visit (three in the placebo arm and one in the testosterone arm). Three of these women discontinued for nonmedical issues unrelated to the study, and one discontinued after experiencing dysfunctional menstrual bleeding for which she requested the blind be broken. She was receiving placebo and did not wish to continue in the study. The overall dropout rate was 16% and was not different between the treatment groups (P = 0.24).

Fig. 1
Fig. 1:
Schematic overview of study enrollment.

Baseline demographics and clinical characteristics

No significant differences were seen between the two groups for any of the baseline variables (Tables 1 and 2). One patient in the testosterone treatment group had a bilateral oophorectomy. Patients were low weight (BMI = 22.4 ± 1.0 vs. 23.2 ± 0.7 kg/m2, P = 0.53, testosterone vs. placebo) and had low androgen levels (1.2 ± 0.1 vs. 1.4 ± 0.2 pg/ml, P = 0.45; testosterone vs. placebo; normal range for women 1.1–6.3 pg/ml; Table 2). Patients also demonstrated low BMD at baseline with reduced T scores at the hip, trochanter, and lumbar spine (Table 1). 25-Hydroxy-vitamin D (28 ± 2 vs. 28 ± 3 ng/ml, P = 0.91) and calcium levels (9.3 ± 0.1 vs. 9.2 ± 0.1 mg/ml, P = 0.38) were not different between the groups at baseline.

Table 1
Table 1:
Baseline demographic characteristics and immune function.
Table 2
Table 2:
Baseline clinical characteristics and treatment effects.

Ninety-two percent of the women were receiving antiretroviral therapy, and no significant difference was seen in baseline immune function or treatment status between the two groups (Table 1). Seventy-five percent or more of the women in each group had undetectable viral load based on the assay used, P = 0.91 (Table 1). The number of women receiving lipid-lowering medications was 17 vs. 15% (P = 0.93). One patient in the placebo group was receiving a stable metformin regimen upon study entry. No other patients were receiving antidiabetic medications.

Treatment effects from baseline to 18 months

Hormone levels

Testosterone treatment resulted in a significant increase in both free and total testosterone levels (change in free testosterone at 18 months, 7.9 ± 1.8 vs. 0.3 ± 0.4 pg/ml, P = 0.002; change in total testosterone at 18 months, 104 ± 24 vs. 2 ± 4 ng/dl, P = 0.001, testosterone vs. placebo; Table 2). Free testosterone levels achieved at 18 months were 6.8 (5.2–15.5) pg/ml [median, interquartile range (IQR); normal range 1.1–6.3 pg/ml]. Estradiol, LH, FSH, and SHBG did not change significantly between the treatment groups over 18 months (Table 2).

Weight and body composition

Lean body mass increased significantly among those in the testosterone treatment group compared with placebo (1.8 ± 0.5 vs. 0.8 ± 0.9 kg, P = 0.04; Table 2, Fig. 2), whereas no significant change was observed between the two groups for total body fat. Weight and BMI increased significantly in the testosterone treatment group compared with placebo (Table 2, Fig. 2).

Fig. 2
Fig. 2:
Individual responses for variables from baseline to 9 months and baseline to 18 months. Individual responses for key variables represent change after 9 months (a) and after 18 months (b). Treatment responses above the 0 line indicate positive responders. BMD, bone mineral density. The overall P values by longitudinal linear effects modeling include total hip bone mineral density (P = 0.02), BMI (P = 0.03), lean mass (P = 0.04), and fat mass (P = 0.16).

Bone mineral density

BMD increased among the testosterone treatment group at the total hip (0.01 ± 0.01 vs. −0.01 ± 0.01 g/cm2, P = 0.02, testosterone vs. placebo) and trochanter (0.01 ± 0.01 vs. −0.02 ± 0.01 g/cm2, P = 0.01, testosterone vs. placebo, Fig. 2). A significant change in BMD was not observed at the lumbar spine (Table 2).

Immune function

Neither HIV log10 viral load nor CD4 cell count differed between the treatment groups at 9 months [median (IQR), 2.6 (2.6–3.1) vs. 2.6 (2.6–2.8) copies, P = 0.61; 384 (262–640) vs. 478 (352–724) cells/μl, P = 0.28, testosterone vs. placebo] or 18 months [median (IQR), 2.6 (2.6–2.6) vs. 2.6 (2.6–2.6) copies, P = 0.41; 511 (248–608) vs. 532 (416–792) cells/μl, P = 0.26, testosterone vs. placebo]. The percentages with suppressed viral load at 9 months (64 vs. 73%, P = 0.65) and 18 months (75 vs. 89%, P = 0.42), testosterone vs. placebo, were not different between treatment groups.

Quality of life

Testosterone treatment significantly improved depression indices, (−6.8 ± 2.2 vs. −1.9 ± 3.1, P = 0.02, testosterone vs. placebo) and problems affecting sexual function compared with the placebo group, although changes were not observed for the other domains of the BISF-W (Table 2).

Compliance

All used and unused patches were collected every 6 weeks to measure study medication compliance. Compliance did not differ between the treatment groups (98 vs. 97%, P = 0.40, testosterone vs. placebo).

Safety

Statistically significant differences in liver function and lipid levels were not observed between the treatment groups, and fasting glucose decreased in the testosterone compared with placebo patients (Table 2). Hirsutism scores did not differ significantly between the two groups at 18 months (0.1 ± 0.1 vs. 0.0 ± 0.4, P = 0.81; testosterone vs. placebo).

No serious study-related adverse events occurred during the randomized portion of the study. The frequency of important adverse events potentially related to testosterone administration is shown in Table 3, and the frequencies of these events did not differ between treatment groups. Acne was reported in four patients receiving testosterone and three patients receiving placebo (P = 0.75). None of the patients required a dose reduction.

Table 3
Table 3:
Adverse events potentially related to testosterone administration.

Discussion

This study is the first to investigate the effects of testosterone use over 18 months among HIV-infected women. Similar to other short-term studies [1,6,10,11], we now show that testosterone is well tolerated over a long treatment period. In addition, we demonstrate that testosterone use among HIV-infected women with relatively low androgen levels, weight, and BMD resulted in a significant increase in lean mass, weight, BMD at the hip and trochanter, and improvement in quality of life indices. Prior data demonstrate that low androgen levels are common among HIV-infected women [1–4], suggesting a sizable population that might benefit from testosterone administration. Low androgen levels are seen among HIV-infected women even in the current era of HAART, as 31 out of 35 women met the criterion for relative androgen deficiency in this study and at least 50% met a definition of relative androgen deficiency in a prior study [6].

Patients randomized to testosterone experienced a significant increase in both free and total testosterone levels without simultaneous effects on estradiol. This suggests that minimal testosterone was aromatized to estrogen, consistent with prior investigations of transdermal testosterone use at this dose [11,12]. Contrary to the findings of a prior study with the same testosterone dose [6], transdermal testosterone use in our study had no significant effect on lipid levels, including high-density lipoprotein, and the number of women receiving lipid-lowering medications did not differ between treatment groups.

Study-related adverse events were similar between groups, without significant differences in hirsutism score, hair pattern, acne or skin irritation, or changes in menstrual pattern. The frequency of adverse events was consistent with that seen in other studies utilizing transdermal testosterone at similar or lower doses in HIV-infected women [1,11], and none of the patients withdrew related to such events, except for one women receiving placebo who withdrew for a change in menstrual pattern. Immune function remained stable.

Testosterone use resulted in a significant increase in lean mass in this long-term study. Prior testosterone treatment studies of a lower dose or shorter duration or both did not show an effect on lean mass among HIV-infected women [1,3,6]. A significant effect of testosterone given at the same dose as used in this study was shown in a long-term study of HIV-negative women over a 12-month period [11]. We selected patients who were at normal to low weight and therefore, more likely to have lost lean body mass at baseline. Moreover, we chose patients on the basis of low androgen levels. Indeed, 91% of HIV-infected women screened demonstrated a testosterone level below the cut-off chosen, with mean baseline levels very close to the lower end of the normal range. Women chosen for this study, with relatively low testosterone, may have been more likely to benefit than HIV-infected women with higher androgen levels.

Weight also increased in the testosterone group over 18 months. The women were of stable, relatively low weight at baseline, and the increase in BMI may be related to the increase in lean mass. In addition, this increase in BMI did not adversely affect insulin levels, potentially because patients were at relatively low weight at the beginning of the study. Indeed, those randomized to testosterone actually demonstrated a significant reduction in fasting glucose compared with placebo over 18 months, suggesting an improvement in overall glucose homeostasis. This improvement may be related to increased muscle mass for glucose disposal, but further studies are needed to verify this effect and determine its mechanism. Caloric intake did not change significantly between the groups over the course of the study.

Our study demonstrates beneficial effects of testosterone on BMD among HIV-infected women. Prior investigations have reported reduced BMD among women with HIV and androgen deficiency [13,14], although no study to date has been long enough to examine the effects of testosterone treatment on BMD in this population. BMD was reduced at all sites among the women in this study at baseline, consistent with prior data demonstrating that HIV-infected women with low androgen levels are at a higher risk for bone loss. We demonstrate that testosterone use increased BMD at the hip and tronchanter, although no effect was seen for the lumbar spine. Similar results were seen among non-HIV-infected women with hypopituitarism treated with the same testosterone dose for 12 months [11]. These data suggest that cortical, rather than trabecular bone, may be more responsive to testosterone administration. Estradiol levels did not increase in response to testosterone, arguing against increased estradiol levels as a mechanism for increased BMD. The effects on BMD may be directly related to the anabolic effects of testosterone on bone [15,16] or via indirect effects related to increased lean body mass and weight seen in response to testosterone [13,14,17].

A significant effect on mood and problems affecting sexual function was seen among those in the testosterone treatment group. At baseline, mean scores on the BDI were consistent with ‘mild-to-moderate’ depression. A significant improvement was seen in response to testosterone, with mean scores suggesting ‘no or minimal’ depression in the testosterone group after 18 months, although individual responses varied. A beneficial effect of testosterone on depression and mood scores was not seen in prior studies of testosterone administration among women with HIV [1], although a lower dose of testosterone was used for only 6 months. In contrast, a beneficial effect of testosterone administration on mood was reported among androgen-deficient women with hypopituitarism over 12 months [11]. In our study, testosterone use resulted in a significant decrease in the number of problems affecting sexual function, although it did not have an effect on other domains present in the questionnaire. Testosterone use in postmenopausal women has also been associated with improvement in some aspects of sexual function, although studies are limited [18]. Other studies of testosterone use (300 μg) have showed improvement in libido and sexual function among women with bilateral oophorectomy [12] and also among women with hypopituitarism [11].

This study has a number of limitations. Although testosterone was well tolerated over 18 months, without signs of virilization, and patients with low levels were specifically chosen, testosterone levels did rise above the normal range in a number of patients. The levels achieved were similar to those reported in the investigator brochure and in the recent study by Davis et al.[19] among non-HIV-infected women. Transdermal testosterone administration is not approved for use in the United States. A transdermal testosterone product identical to the one used in this study is approved for the treatment of sexual dysfunction in oophorectomized women in Europe, although it is not approved for other indications or for use in HIV-infected women. Although these data from a relatively small but long-term pilot study are very encouraging, the long-term safety of such a strategy needs to be investigated and confirmed in larger studies before it can be recommended clinically. Future studies will need to assess effects of long-term testosterone on risk for breast cancer, endometrial cancer, hirsutism, and menstrual pattern. We assessed pregnancy tests frequently in the current study, as testosterone use is potentially harmful to pregnant women.

Women with HIV are known to have reduced BMD, lean body mass, and reduced quality of life. Low androgen levels are common in this population and may contribute to such changes; yet, no treatment strategies exist for women, and research investigating sex-specific treatment strategies in HIV-infected women has been very limited. In contrast, among HIV-infected men, treatment of hypogonadism is routine and improves body composition, BMD, and depression [20,21]. Data from this study suggest that testosterone (300 μg twice weekly) is well tolerated over 18 months and results in significant effects on body composition, BMD, and quality of life indices. Further studies of long-term testosterone are necessary in women with HIV, as this treatment strategy may ultimately prove useful for the large number of such women with low androgen levels, bone loss, and reduced quality of life.

Acknowledgements

We would like to thank the patients who participated in the study, the bionutrition, nursing, and support staff at the MGH GCRC, and the bionutrition staff at the MIT GCRC for their dedicated patient care. Viral load testing was performed by the Emory Center for AIDS Research, Emory University, Atlanta, Georgia, USA.

This study was funded by NIH DK-R01 054167 (S.G.), M01-RR-01066, 1 UL1 RR025758-01, and the Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. Procter and Gamble provided transdermal testosterone and blinded placebo patches but did not participate in study design, analysis, or manuscript preparation.

S.E.D.L. contributed to the study recruitment, research subject management, data analysis and interpretation, and manuscript preparation. M.C. contributed to data management, the coordination of study appointments/patients, and manuscript preparation. H.L. contributed to data analysis and interpretation and manuscript preparation. S.G. contributed to the study conception, design, data analysis and interpretation, and manuscript preparation.

Clinical trials identifier, NCT00095212.

References

1. Dolan S, Wilkie S, Aliabadi N, Sullivan MP, Basgoz N, Davis B, Grinspoon S. Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized, placebo-controlled study. Arch Intern Med 2004; 164:897–904.
2. Grinspoon S, Corcoran C, Stanley T, Rabe J, Wilkie S. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome. J Clin Endocrinol Metab 2001; 86:4120–4126.
3. Miller K, Corcoran C, Armstrong C, Caramelli K, Anderson E, Cotton D, et al. Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab 1998; 83:2717–2725.
4. Grinspoon S, Corcoran C, Miller K, Biller BM, Askari H, Wang E, et al. Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting [erratum appears in J Clin Endocrinol Metab 1997; 82:3360]. J Clin Endocrinol Metab 1997; 82:1332–1337.
5. Dolan SE, Carpenter S, Grinspoon S. Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women. J Acquir Immune Defic Syndr 2007; 45:161–167.
6. Choi HH, Gray PB, Storer TW, Calof OM, Woodhouse L, Singh AB, et al. Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab 2005; 90:1531–1541.
7. Roche AF, Sievogel RM, Chumlea WC, Webb P. Grading body fatness from limited anthropometric data. Am J Clin Nutr 1981; 34:2831–2838.
8. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4:561–571.
9. Mazer NA, Leiblum SR, Rosen RC. The brief index of sexual functioning for women (BISF-W): a new scoring algorithm and comparison of normative and surgically menopausal populations. Menopause 2000; 7:350–363.
10. Miller KK, Biller BM, Schaub A, Pulaski-Liebert K, Bradwin G, Rifai N, Klibanski A. Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism. J Clin Endocrinol Metab 2007; 92:2474–2479.
11. Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2006; 91:1683–1690.
12. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000; 343:682–688.
13. Huang JS, Wilkie SJ, Sullivan MP, Grinspoon S. Reduced bone density in androgen-deficient women with acquired immune deficiency syndrome wasting. J Clin Endocrinol Metab 2001; 86:3533–3539.
14. Dolan S, Carpenter C, Grinspoon S. Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women. J Acquir Immune Defic Syndr 2007; 45:161–167.
15. Labrie F, Diamond P, Cusan L, Gomez JL, Belanger A, Candas B. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997; 82:3498–3505.
16. Raisz LG, Wiita B, Artis A, Bowen A, Schwartz S, Trahiotis M, et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab 1996; 81:37–43.
17. Miller KK, Biller BM, Hier J, Arena E, Klibanski A. Androgens and bone density in women with hypopituitarism. J Clin Endocrinol Metab 2002; 87:2770–2776.
18. Bhasin S, Enzlin P, Coviello A, Basson R. Sexual dysfunction in men and women with endocrine disorders. Lancet 2007; 369:597–611.
19. Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008; 359:2005–2017.
20. Grinspoon S, Corcoran C, Askari H, Schoenfeld D, Wolf L, Burrows B, et al. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998; 129:18–26.
21. Grinspoon S, Corcoran C, Stanley T, Katznelson L, Klibanski A. Effects of androgen administration on the growth hormone-insulin-like growth factor I axis in men with acquired immunodeficiency syndrome wasting. J Clin Endocrinol Metab 1998; 83:4251–4256.
Keywords:

AIDS; HIV; testosterone; women

© 2009 Lippincott Williams & Wilkins, Inc.