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Background The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown.
Methods We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 µg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes.
Results At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 µg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 µg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 µg per day, P<0.001; 150 µg per day, P=0.04) and decreases in distress (300 µg per day, P<0.001; 150 µg per day, P=0.04). The rate of androgenic adverse events — primarily unwanted hair growth — was higher in the group receiving 300 µg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization.
Conclusions In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 µg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495
[ClinicalTrials.gov]
.)
Methods
Study Population
Women from 65 centers in the United States, Canada, Australia, the United Kingdom, and Sweden participated in the study between July 2004 and February 2006. To participate, women with surgically induced menopause had to be 20 to 70 years of age and postmenopausal for at least 12 months; women who had undergone natural menopause had to be 40 to 70 years of age and postmenopausal for at least 2 years. Participants who were 40 years of age or older had to have had a normal screening mammogram for both breasts within the previous 12 months. All participants had to have had a normal Papanicolaou (Pap) smear within the previous 2 months, no evidence of endometrial cancer or hyperplasia, and a level of sex hormone–binding globulin above 12 nmol per liter (the lower limit of the normal range for the central laboratory). Women had to be in a stable, monogamous relationship with a sexually functional partner for at least 1 year before study entry, and partners were expected to be physically present for at least 50% of each month during the study. Women were considered to have hypoactive sexual desire disorder if they answered yes to five questions about changes in their sex life after menopause, including decreases in the levels of desire and sexual activity that concerned them; these criteria were consistent with the definition of the disorder in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).14,21 Exclusion criteria were the use of systemic estrogen or estrogen plus progestin during the previous 3 months; any androgen therapy during the previous 3 months (7 months for implantable testosterone); any serious medical condition, a psychiatric disorder, dyspareunia, a history of breast or gynecologic cancer, or physical limitations; and the use of nutritional supplements or medications, such as antidepressants, that were likely to affect sexual function.
Concomitant medications with the potential to affect the study medication's safety profile or interpretation of the results were not permitted during the study. Participants were restricted from starting vaginal estrogen or phytoestrogens and were encouraged to maintain their current dose and regimen of vaginal estrogen or phytoestrogens, if applicable.
All women gave written informed consent to participate, and the appropriate ethics committees approved the protocol and informed consent form. The study's sponsor, Procter & Gamble Pharmaceuticals, was involved in the design of the trial and collection of data and conducted the data analysis according to the predefined statistical analysis plan. The academic authors wrote the manuscript, had unrestricted access to the study data, and vouch for the accuracy and completeness of the reported analyses.
Study Design
Eligibility and screening procedures, including breast and pelvic examinations, Pap smears, and collection of blood samples, were performed at the pretreatment visit (4 weeks before study entry). Women were stratified according to whether they had undergone natural or surgically induced menopause and were then randomly assigned by the method of random permuted blocks to receive placebo, 150 µg of testosterone per day, or 300 µg of testosterone per day for 52 weeks. Participants were seen at the study centers at baseline and at weeks 6, 12, 24, 36, and 52. Efficacy was measured through week 24; safety was assessed through week 52.
During the first year, women were given the option of continuing their randomized treatment for an additional year so that further safety data could be collected; the extension continued through January 2007. Women were excluded from the study extension if they had a clinically significant abnormal physical finding at the week-52 visit or if any adverse event had occurred that made continuation unsafe (as determined by the investigator or the medical monitor). Women who had commenced any other systemic hormonal therapy were also excluded from the extension. All other participants who completed the first year were invited to continue receiving their randomly assigned treatment (participants, investigators, study-center personnel, and study monitors remained unaware of the treatment assignments throughout this period). Findings from the extension phase are reported separately and in brief, since the data were from a selected subpopulation, with only 38.6% of the patients who completed week 52 participating.
Treatment
Each participant applied two patches — one measuring 28 cm2 and the other 14 cm2 — twice weekly to the abdomen. In the placebo group, both were placebo patches. In the group receiving 150 µg of testosterone per day, the smaller patch (14 cm2) delivered approximately 150 µg of testosterone per day, and the larger one (28 cm2) was a placebo patch. In the group receiving 300 µg of testosterone per day, the larger patch delivered approximately 300 µg of testosterone per day, and the smaller one was a placebo patch. The patches were identical in appearance for each size. All participants, investigators, and study personnel were unaware of the treatment assignments.
Clinical Measurements
Efficacy Measurements
Efficacy measurements for quantifying treatment effects, previously developed among populations of menopausal women with hypoactive sexual desire disorder, included the weekly Sexual Activity Log,22 the Profile of Female Sexual Function (with scores ranging from 0 to 100 for each domain and a score of less than 40 in the sexual-desire domain indicating low sexual desire),23,24 and the Personal Distress Scale, which measures distress associated with low desire (with scores ranging form 0 to 100 and a score of more than 40 indicating distress).25,26 Each of these instruments was developed by Procter & Gamble. The use of these instruments has been described elsewhere.11,12,14,15,16 The Sexual Activity Log was completed weekly throughout screening and the 24-week study period. The Profile of Female Sexual Function and the distress scale were completed at baseline and at weeks 12 and 24.
Safety Assessments
Adverse events and their severity were assessed at each visit. Facial hair was assessed with the use of the Lorenzo Pictorial Rating Scale (which ranges from 0 to 4, with a higher score indicating more hair growth).27 Adverse events included facial hair growth, assessed on the basis of the depilatory history and the investigators' observations; facial acne, scored with the use of the Palatsi scale (range, 0 to 3, with an increase in the score of 1 or more considered an adverse event)28; changes in voice and the amount and pattern of scalp hair, as reported on questioning of participants; and patch-site symptoms. Physical examinations, including breast and pelvic examination, were periodically performed. Pap testing, bilateral mammography for women 40 years of age or older, and transvaginal ultrasonography for women with a uterus were performed at baseline and at week 52. Women who had not undergone a hysterectomy and who gave consent for endometrial biopsy underwent this procedure at baseline and at week 52. Vital signs, weight, and any vaginal bleeding were recorded at each visit. Blood samples were collected at weeks 24 and 52 for laboratory measurements.
Hormone Measurements
Serum levels of free and total testosterone and sex hormone–binding globulin (assessed at baseline and weeks 12, 24, and 52), bioavailable testosterone (assessed at baseline and week 24), and total dihydrotestosterone, free and total estradiol, and estrone (all assessed at baseline and weeks 24 and 52) were measured by validated methods (Quest Diagnostics), as described elsewhere.11,12,14,15,16
Study Extension
For women who participated in the safety assessments extended through a second year, the assessments were made at weeks 78 and 104, and hormone levels were measured at week 104. These assessments were performed as described above.
Statistical Analysis
An intention-to-treat approach was used, with all women undergoing randomization who received at least one application of study medication included in the analyses. The primary efficacy end point was the change from baseline in the 4-week frequency of satisfying sexual events during weeks 21 through 24. A last-observation-carried-forward approach was used to account for women who discontinued the study; for these women, data from the final 4 consecutive weeks of the Sexual Activity Log were included in the analysis. All tests were two-sided (alpha level, 0.05).
Groups were compared with the use of a nonparametric analysis of covariance (ANCOVA) model adjusted for menopausal type (natural or surgically induced).29 A closed test procedure was adopted, with the treatment effect of 300 µg of testosterone per day, then that of 150 µg of testosterone per day, compared with placebo to control for a type I error (alpha level, 0.05). We used 1% Winsorized means to estimate the mean treatment effect by group. An analysis of variance (ANOVA) model with factors for menopausal type and treatment group was used to analyze changes in secondary efficacy end points. Treatment effect was also assessed according to menopausal type. Post hoc ANOVA analyses were conducted to assess the interaction between the effect of treatment and baseline free testosterone levels (categorized in thirds) and menopausal type. In patients treated with testosterone, the relationship among the free testosterone level, efficacy outcomes, and incidence of androgenic adverse events during the 52-week, double-blind period was assessed with the use of Spearman's rank correlation coefficients and logistic-regression analyses. Continual accumulation of testosterone after baseline and changes from baseline in other hormonal measures were assessed by means of repeated-measures ANOVA in which the effect of linear time trend on log-transformed hormone concentrations was assessed.
Results
Of 1359 women screened, 814 were randomly assigned to a study group (Figure 1), of whom approximately 71% completed 24 weeks and 57% completed 52 weeks (151 in the placebo group, 147 in the group receiving 150 µg of testosterone per day, and 166 in the group receiving 300 µg of testosterone per day). A total of 589 participants (72%) either completed 52 weeks or had a follow-up visit at week 52 after earlier withdrawal.
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At baseline, approximately 50% of all sexual episodes were satisfying. The increase in the 4-week frequency of satisfying sexual episodes from baseline to week 24 was significantly greater in the group receiving 300 µg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but was not significantly greater in the group receiving 150 µg of testosterone per day than in the placebo group (an increase of 1.2 episodes vs. 0.7, P=0.11) (Figure 2). By week 24, 78% of sexual episodes were satisfying in the group receiving 300 µg of testosterone per day as compared with 65% in the placebo group. A significant increase in the frequency of satisfying sexual episodes in the group receiving the higher testosterone dose as compared with the placebo group was evident as early as the second month of treatment and continued throughout the 24-week evaluation period.
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Safety and Adverse Events
The overall incidence of adverse events over a period of 52 weeks was similar among the study groups, and most events were mild and reported by the site investigators as not clearly related to treatment. Few serious adverse events were reported, and rates of these events were similar among the groups (Table 2).
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Clitoral enlargement developed in one woman in the group receiving 150 µg of testosterone per day and in three women in the group receiving 300 µg per day; in all four women, clitoral enlargement was classified as mild by the site investigators. None of these women withdrew from the study, and subsequent examination revealed resolution of clitoral enlargement in the woman receiving the lower dose of testosterone and no further changes in the women receiving the higher dose.
Breast cancer was diagnosed in three women in the testosterone groups between 4 and 12 months after treatment initiation (Table 2), one of whom reported in retrospect a bloody nipple discharge before randomization.
In the group receiving 300 µg of testosterone per day, more women who had not undergone hysterectomy (10.6%) reported vaginal bleeding as compared with the other groups (placebo, 2.6%; 150 µg of testosterone per day, 2.7%). Most cases were reported as mild. The median duration of vaginal bleeding was similar among the groups (placebo group and group receiving 150 µg of testosterone per day, 2.0 days; group receiving 300 µg of testosterone per day, 1.5 days). The frequency of bleeding was not significantly higher with an increased duration of therapy. All women with vaginal bleeding underwent biopsy (13 women), transvaginal ultrasonography (10 women), or both. Two of the women receiving 300 µg of testosterone per day who underwent biopsies had proliferative endometrium. No cases of endometrial hyperplasia or carcinoma were diagnosed.
The groups did not differ significantly with respect to serum lipid or lipoprotein profiles, measures of carbohydrate metabolism, liver function, or other laboratory tests, and within each group, there were no clinically relevant changes from baseline in any of these variables (see Table 1 in the Supplementary Appendix, available with the full text of this article at www.nejm.org) or in vital signs or weight (data not shown). Levels of free, bioavailable, and total testosterone and total dihydrotestosterone showed dose-related increases with testosterone treatment (see Table 3 in the Supplementary Appendix). Changes in the frequency of satisfying sexual episodes were significantly correlated with changes in levels of serum free testosterone at week 24 (Spearman's rank correlation coefficient, 0.26; P<0.001). Median concentrations of free and bioavailable testosterone, as well as concentrations ranging from the 10th to the 90th percentile, remained within the reference ranges for premenopausal women30 during the evaluation periods (see Table 3 in the Supplementary Appendix).
Study Extension
Of the 464 women who completed 52 weeks of treatment, 179 agreed to continue receiving their randomly assigned treatment for an additional year; 132 completed 104 weeks of assigned therapy. The women who participated in the extension phase of the study had demographic and baseline characteristics that were similar to those of the initial study population. No clinically relevant changes were noted for vital signs, weight, or biochemical or hematologic variables through week 104. Serum androgen levels during the extension period did not vary materially from those in year 1. In one woman treated with 300 µg of testosterone per day for 104 weeks, an infiltrating ductal breast cancer was detected by mammography 3 months after study cessation; her mammogram at week 52 was reported to be normal. She had been an estrogen user for 27 years before the study began and reported having a sister who had breast cancer.
Discussion
This study shows that testosterone therapy provides some benefit in the treatment of hypoactive sexual desire disorder in postmenopausal women who are not concurrent users of estrogen or estrogen plus progestin. We found significant improvements in the mean frequency of satisfying sexual episodes, which although numerically modest (an increase of 2.1 episodes per month in the group receiving 300 µg of testosterone per day as compared with 0.7 in the placebo group at 24 weeks, or a difference of 1.4 episodes) were similar to those previously shown by others to be clinically meaningful31 and were associated with increases in sexual desire, arousal, orgasm, and pleasure and a reduction in personal distress. Efficacy was measured only for 24 weeks, since efficacy has previously been reported to reach a plateau at 24 weeks.32
Community-based studies indicate that many postmenopausal women continue to be sexually active despite a high level of sexual dissatisfaction,1 engaging in sexual activity to please their partner and maintain domestic harmony.33 Women were recruited to this study if they reported significant loss of sexual desire that was causing personal distress. A cut-off level of serum testosterone was not an inclusion criterion, since a single measurement of the serum testosterone level in women presenting with low sexual desire is not useful for diagnosing "androgen insufficiency" in women.34
Previous blinded studies have shown that women treated with a patch delivering 300 µg of testosterone per day were more likely to report a meaningful benefit than women receiving placebo, with more than 85% of those reporting a benefit wishing to continue treatment.35 However, prior studies of testosterone therapy in postmenopausal women have been limited to those taking estrogen, primarily because of concern that without concurrent estrogen therapy, exogenous testosterone might be ineffective36 or have adverse effects on lipid levels, glucose metabolism, or the breast.37,38 Our findings are consistent with previous studies that have shown the side-effect profile of the testosterone patch to be acceptable to women with hypoactive sexual desire disorder who had undergone surgically induced menopause and were taking estrogen (1172 women)11,12,13,14,15 or who had undergone natural menopause and were taking estrogen with a progestin (549).16 Our findings are also consistent with a recent study of transdermal testosterone in premenopausal women with low libido that showed an increase in satisfying sexual episodes with the administration of testosterone therapy as compared with placebo.39
Except for a higher incidence of hair growth reported by women assigned to testosterone in the present study, the incidence of androgenic adverse events was similar to that observed in prior studies of similar duration.11,12,13,14,15,16 The increased hair growth observed during the study was not significantly related to higher serum testosterone levels. This observation may reflect heterogeneous receptor sensitivity to testosterone action in the study population. Despite the increased incidence of hair growth, women receiving 300 µg of testosterone per day were not more likely to discontinue therapy than the women in the other groups. There was no evidence of continued accumulation of free or total testosterone concentrations over the 52-week study period or during the study extension. Concentrations of sex hormone–binding globulin, free and total estradiol, and estrone showed no clear patterns of change over time. Concentrations of free testosterone at 52 weeks in the group receiving 300 µg of testosterone per day appeared to be high relative to the reference range for premenopausal women up to 49 years of age and approximated the mean level for women 18 to 24 years of age (6.80 pg per milliliter [23.53 pmol per liter]; 10th to 90th percentile, 3.72 to 11.13 [12.87 to 38.51]).34
Breast cancers were detected during the primary study in three women assigned to the testosterone groups (one of whom later reported having had symptoms before randomization; cancer was diagnosed in one of the other two women after only 4 months of therapy). An additional case of breast cancer was reported in one of the testosterone groups at the completion of the study extension. The excess of cases of breast cancer in women treated with testosterone may be due to chance. However, the possibility of a causal relationship must be considered. Some epidemiologic studies have shown that endogenous and exogenous testosterone is associated with the risk of breast cancer,38,40 but others have not. Some data suggest that the inclusion of testosterone in regimens of estrogen plus progestin may ameliorate the stimulating effects of hormones on the breast.41,42 Long-term data from large clinical trials of testosterone use are lacking.36,43
The fact that vaginal bleeding was reported more frequently in the group receiving 300 µg of testosterone per day probably reflects the atrophic effect of testosterone on the endometrium,44 and investigation did not reveal serious endometrial disease. The study extension did not reveal additional safety concerns, but these data should be interpreted with caution, since they involve a selected subgroup of the study population and follow-up was not continued beyond the second year. The study was not sufficiently large or long to assess the safety of long-term testosterone use.
In conclusion, use of the patch delivering 300 µg of testosterone per day significantly improved sexual function and decreased distress in postmenopausal women who were not receiving estrogen therapy; the increase in the frequency of satisfying sexual episodes was modest but appeared to be clinically meaningful. These findings indicate that exogenous estrogen or combined estrogen and progestin are not required for testosterone to be effective in the treatment of hypoactive sexual desire disorder. Additional data are needed to assess the long-term safety of testosterone use in women with estrogen depletion.
Supported by research grants from Procter & Gamble Pharmaceuticals.
Dr. Davis reports receiving consulting fees from Acrux, AstraZeneca Oncology Australia, Organon, and Procter & Gamble Pharmaceuticals, lecture fees from AstraZeneca Oncology Australia and Organon, and grant support from AstraZeneca Pharmaceuticals, Novartis Oncology Australia, and Procter & Gamble Pharmaceuticals; Dr. Kroll, grant support from BioSante and Procter & Gamble Pharmaceuticals; Dr. Bouchard, consulting fees for the Canadian Advisory Board of Procter & Gamble Pharmaceuticals and sponsorship from Procter & Gamble Pharmaceuticals to attend one European Society for Sexual Medicine Annual Meeting and one International Society for the Study of Women's Sexual Health Meeting; Dr. Panay, consulting and lecture fees from Procter & Gamble Pharmaceuticals; Dr. Gass, consulting fees from Palatin Technologies, Procter & Gamble Pharmaceuticals, Upsher–Smith Laboratories, and Wyeth Pharmaceuticals and grant support from Boehringer Ingelheim, Procter & Gamble Pharmaceuticals, and Wyeth Pharmaceuticals; and Dr. Braunstein, consulting fees from Novartis, Mattern Pharmaceuticals, Esoterix, and Abbott Diagnostics and grant support from Procter & Gamble Pharmaceuticals and BioSante Pharmaceuticals. Drs. Rodenberg, Pack, and Koch report being employed by Procter & Gamble Pharmaceuticals. Dr. Moufarege reports being a former employee of Procter & Gamble Pharmaceuticals and owning stock options in the company. No other potential conflict of interest relevant to this article was reported.
We thank Akshay Buch, Ph.D., for help with the study design and data review, Chad Melson for his contribution to the data analysis, and Richard Helmchen for assistance in the preparation of the manuscript.
Source Information
From the Women's Health Program, Monash University, Alfred Hospital, Prahran, Australia (S.R.D.); Centre d'Étude Clinique, Montreal (M.M.); Women's Clinical Research Center and the Menopause Center of Seattle, Seattle (R.K.); Université Laval, Quebec, QC, Canada (C.B.); Queen Charlotte's and Chelsea Hospital, London (N.P.); University of Cincinnati College of Medicine, Cincinnati (M.G.); Cedars–Sinai Medical Center, Los Angeles (G.D.B.); Karolinska University Hospital, Stockholm (A.L.H.); Procter & Gamble Pharmaceuticals, Mason, OH (C.R., S.P., H.K.); Debiopharm Group, Charenton-le-Pont, France (A.M.); and Chelsea and Westminster Hospital, London (J.S.).
Address reprint requests to Dr. Davis at the Women's Health Program, Department of Medicine, Monash University, Alfred Hospital, Commercial Rd., Prahran VIC 3181, Australia, or at susan.davis{at}med.monash.edu.au.
References
The following investigators participated in the APHRODITE trial: Monash Medical School, Alfred Hospital, Prahran, Australia — S. Davis; Sydney Menopause Centre, Royal Hospital for Women, Randwick, Australia — J. Eden; ReproMED Building, Dulwich, Australia — R. Norman; Betty Byrne Henderson Women's Health Research Centre, Royal Brisbane and Women's Hospital, Herston, Australia — S. O'Neill; Keogh Institute for Medical Research, Sir Charles Gairdner Hospital, Nedlands, Australia — B. Stuckey; Sydney Centre for Reproductive Health Research, Ashfield, Australia — E. Weisberg; Karolinska University Hospital, Stockholm — A. Lindén Hirschberg; Kvinnoläkarna AB, Västerås, Sweden — M. Linde; Kvinnokliniken, Danderyd, Sweden — A. Rådestad; Urogynecology Associates of Colorado, Denver — O. Aguirre; LifeSpan Research, Palo Alto, CA — D. Baldwin; Phase II Center for Women's Health, Salt Lake City — P. Bearnson; Cedars–Sinai Medical Center, Los Angeles — G. Braunstein; Tennessee Women's Care, Nashville — P. Bressman; UT Medical Group, Germantown, TN — C. Brown; Baylor College of Medicine, Houston — J. Buster; Radiant Research–Birmingham, Birmingham, AL — G. Conner; Johns Hopkins Center for Sexual Health and Medicine, Lutherville, MD — L. Derogatis; Women's Health Care at Frost Street, San Diego, CA — P. Dietze, Jr.; Center for Pharmaceutical Research, Kansas City, MO — J. Ervin; Reproductive Medicine Research, Holmes Hospital, Cincinnati — M. Gass; Clinical Research Institute of South Florida, Aventura — C. Goldsmith; Sexual Wellness Center, Annapolis, MD — A.T. Goldstein; Comprehensive NeuroScience, Atlanta — S. Gordon; Medical Group of Northern Nevada, Reno — L. Ho; Radiant Research–San Antonio, San Antonio, TX — W. Jennings; Foundation for Osteoporosis Research and Education, Oakland, CA — R. Kagan; QUEST Research Institute, Southfield, MI — N. Kakos; Cincinnati — M. Katz; MacDonald Physicians, Mayfield Heights, OH — S. Kingsberg; Women's Clinical Research Center, Seattle — R. Kroll; North Country Internal Medicine, Vista, CA — J. LaFata; Hillcrest Medical Group, Tulsa, OK — S. Landgarten; Center for Marital and Sexual Health, Beachwood, OH — S. Levine; Radiant Research–Chicago, Chicago — P. Marx; National Clinical Research, Richmond, VA — J. McKenney; Radiant Research–Scottsdale, Scottsdale, AZ — B. Miller; Tidewater Physicians for Women, Norfolk, VA — F. Morgan, Jr.; New York University School of Medicine, New York — L. Nachtigall; Radiant Research–Cincinnati, Cincinnati — M. Noss; Comprehensive NeuroScience, St. Petersburg, FL — M. Nunez; Heartland Research Associates, Wichita, KS — T. Poling; Westlake Medical Research, Westlake Village, CA — E. Portnoy; Atlanta North Gynecology, Roswell, GA — H. Reisman; Radiant Research–Dallas North, Dallas — M. Reynolds; Radiant Research–Irvine, Irvine, CA — E. Lee; Tampa Bay Medical Research, Clearwater, FL — J. Rothman; Coastal Clinical Research, Mobile, AL — R. Shields; Massachusetts General Hospital, Boston — J. Shifren; Women's Health Research Center, Laurel, MD — J. Simon; Northeast Indiana Research, Fort Wayne — G. Singh; Baylor Medical Center at Irving, Irving, TX — W.T. Dickey; Rapid Medical Research, Cleveland — W. Utian; Downtown Women's Health Care, Denver — A. Waldbaum; Diablo Clinical Research, Walnut Creek, CA — R. Weinstein; nTouch Research, Oklahoma City, OK — N. Williams; Clinique RSF–Québec, Quebec, QC, Canada — C. Bouchard; Centre d'Étude Clinique, Montreal — M. Moreau; Salisbury Clinic, Plymouth, United Kingdom — J. Dean; Synexus Clinical Research Centre, Wigan, United Kingdom — J. Fraser; Queen Charlotte's and Chelsea Hospital, London — N. Panay; Women's Centre, Oxford, United Kingdom — M. Rees; Lister Hospital, London — J. Studd; Synexus Clinical Research Centre, Chorley, United Kingdom — S. Taylor; Synexus Clinical Research Centre, Llanishen, United Kingdom — H. Thomas.
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Related Letters:
Testosterone for Low Libido
Basson R., Davis S. R., Rodenberg C.
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N Engl J Med 2009;
360:728-729, Feb 12, 2009.
Correspondence
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