Safety and Efficacy of a Testosterone Metered-Dose Transdermal Spray for Treating Decreased Sexual Satisfaction in Premenopausal Women

A Randomized Trial

15 April 2008 | Volume 148 Issue 8 | Pages 569-577

Background: It is not known whether premenopausal women who report low sexual satisfaction and have low circulating testosterone levels will benefit from testosterone therapy.

Objective: To evaluate the effects of exogenous testosterone in premenopausal women reporting diminished sexual function.

Design: Randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: 6 Australian medical centers.

Patients: 261 women age 35 to 46 years who reported a decrease in satisfying sexual activity relative to their younger years and had a morning serum free testosterone level less than 3.8 pmol/L (<1.1 pg/mL).

Intervention: 3 different doses of testosterone administered by a metered-dose transdermal spray for 16 weeks or placebo.

Measurements: The primary outcome was the mean number of self-reported satisfactory sexual events (SSEs) over 28 days at week 16. The frequency of SSEs, total number of sexual events (every 4 weeks), scores from the modified Sabbatsberg Sexual Self-Rating Scale and the Psychological General Well-Being Index, and safety variables were also measured.

Results: The number of SSEs increased during the treatment period in the active treatment groups and the placebo group. The mean number of SSEs over 28 days at week 16 was statistically significantly greater for women treated with the intermediate dose of testosterone therapy (one 90-µL spray) than for women treated with placebo. The least-squares mean was 2.48 versus 1.70 SSEs, respectively (event rate ratio, 1.49 [95% CI, 1.01 to 2.18]; P = 0.04). The frequency of SSEs in women treated with low and high doses of testosterone did not differ from that in women who took placebo. The rate ratios based on the least-squares mean rates of SSEs during weeks 4 to 16 for each treatment group showed statistically significant or borderline significant increases in all testosterone groups compared with the placebo group. The rate ratios for the one 56-µL spray, one 90-µL spray, and two 90-µL sprays treatment groups were 1.34 (CI, 0.97 to 1.85; P = 0.081), 1.48 (CI, 1.07 to 2.06; P = 0.018), and 1.38 (CI, 1.00 to 1.92; P = 0.052), respectively. At week 16, 95% of women treated with the one 90-µL dose had a free testosterone level less than the upper limit of the reference range for women. The most frequently reported adverse event was hypertrichosis, which was dose-related and mostly confined to the application site. No clinically relevant changes in blood test values, serum biochemical variables, or vital signs occurred.

Limitation: The study duration was short, and the placebo effect was strong.

Conclusion: A daily 90-µL dose of transdermal testosterone improves self-reported sexual satisfaction for premenopausal women with reduced libido and low serum-free testosterone levels by a mean of 0.8 SSE per month. The rate of SSEs with higher and lower testosterone doses did not differ from that with placebo.

Editors' Notes Context Testosterone levels in women gradually decline with age, and supplemental testosterone may improve sexual satisfaction in postmenopausal women. Contribution Sexually active women age 35 to 45 years with low serum free testosterone levels and low sexuality scores were randomly assigned to placebo or 3 doses of transdermal testosterone for 16 weeks. Sexually satisfying encounters increased in all 4 groups. Compared with placebo, the number increased by 0.8 per month with the intermediate dose (P = 0.04) but not with the other doses. Caution The study was too brief to measure adverse events reliably. Implication We need more evidence before prescribing testosterone supplementation to premenopausal women in clinical practice. —The Editors

 

Author and Article Information

From Monash University, Alfred Hospital, Prahran, Victoria, Australia; Research Centre for Reproductive Health, University of Adelaide, School of Paediatrics and Reproductive Health, Adelaide, South Australia, Australia; Royal Hospital for Women, Randwick, New South Wales, Australia; Sydney Centre for Sexual and Relationship Therapy and John Wlodarczyk Consultancy Services, Sydney, New South Wales, Australia; Princess Alexandra Hospital, Brisbane, Queensland, Australia; Sir Charles Gairdner Hospital, University of Western Australia, Perth, Western Australia, Australia; and Acrux Limited, Melbourne, Victoria, Australia.

Australian Clinical Trials Registry number: ACTRN012605000481673.

Reproducible Research Statement: Study protocol, statistical code, and data set: Available to approved individuals through written agreements with research sponsor (Acrux Limited).

Potential Financial Conflicts of Interest: Employment: K. Gard'ner (Acrux Limited), A. Humberstone (Acrux Limited). Consultancies: S. Davis (Acrux Limited), J. Wlodarczyk (John Wlodarczyk Consultancy Services). Stock ownership or options (other than mutual funds): K. Gard'ner (Acrux Limited), A. Humberstone (Acrux Limited). Receipt of payment for manuscript preparation: J. Wlodarczyk (Acrux Limited).

Requests for Single Reprints: Susan Davis, MD, PhD, Women's Health Program, Department of Medicine, Monash University, Alfred Hospital, Commercial Road, Prahran, Victoria 3181, Australia; e-mail, susan.davis{at}med.monash.edu.au.

Current Author Addresses: Drs. Davis and Papalia: Women's Health Program, Department of Medicine, Monash University, Alfred Hospital, Commercial Road, Prahran, Victoria 3181, Australia.

Dr. Norman: Research Centre for Reproductive Health, University of Adelaide, School of Paediatrics and Reproductive Health, Level 6, Medical School North, Frome Road, Adelaide, South Australia 5005, Australia.

Dr. O'Neill: Royal Hospital for Women, Locked Bag 2000, Randwick, New South Wales 2031, Australia.

Dr. Redelman: 35 Spring Street, Bondi Junction, New South Wales 2022, Australia.

Dr. Williamson: Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, 4102, Australia.

Dr. Stuckey: Department of Medicine, Sir Charles Gairdner Hospital, Hospital Avenue Nedlands, Perth, Western Australia 6009, Australia.

Dr. Wlodarczyk: John Wlodarczyk Consultancy Services, 12 Mirral Crescent, New Lambton Heights, New South Wales 2305, Australia.

Ms. Gard'ner and Dr. Humberstone: Nucleus Network, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria 3004, Australia.

Author Contributions: Conception and design: S. Davis, M.A. Papalia, J. Wlodarczyk, A. Humberstone.

Analysis and interpretation of the data: S. Davis, R.J. Norman, J. Wlodarczyk, A. Humberstone.

Drafting of the article: S. Davis, J. Wlodarczyk, A. Humberstone.

Critical revision of the article for important intellectual content: S. Davis, R.J. Norman, S. O'Neill, M. Redelman, B.G.A. Stuckey, J. Wlodarczyk, K. Gard'ner, A. Humberstone.

Final approval of the article: S. Davis, R.J. Norman, M. Williamson, J. Wlodarczyk, K. Gard'ner.

Provision of study materials or patients: S. Davis, M.A. Papalia, R.J. Norman, S. O'Neill, B.G.A. Stuckey, A. Humberstone.

Statistical expertise: S. Davis, J. Wlodarczyk.

Obtaining of funding: S. Davis, A. Humberstone.

Administrative, technical, or logistic support: S. Davis, M.A. Papalia, K. Gard'ner, A. Humberstone.

Collection and assembly of data: S. Davis, S. O'Neill, M. Redelman, B.G.A. Stuckey, K. Gard'ner, A. Humberstone.

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