A Single Centre Study to Describe the Changes in Serum Testosterone Concentration Following Application of Testosterone Gel in Post-Menopausal Women With Hypoactive Sexual Desire Disorder (HSSD) Already Receiving This as Part of Usual Care in Conjunction With Oestrogen-Containing Hormone Replacement Treatment (HRT)

Abstract

Introduction

Hypoactive Sexual Desire Disorder (HSDD) is characterized by a long-term decrease in sexual desire (low-libido) causing personal distress. HSDD predominantly affects post-menopausal women or following oophorectomy. Despite the clear indication that testosterone action could overcome the symptoms of HSDD by elevating testosterone levels, there is little research concerning this. For decades many post-menopausal women have been prescribed off-label testosterone, an approved therapy for men, at a modified dose. The purpose of this study was to conduct an exploratory pharmacokinetic analysis in post-menopausal women with low sexual desire consistent with HSDD already established on treatment with Testosterone gel (Testogel 16.2 mg/g Gel in Pump, Besins Healthcare (UK) Ltd.).

Methods

Twenty-four women applying Testogel 16.2 mg/g via pump once every 3 or 4 days and had been prescribed Testogel 16.2 mg/g for at least 6 months were included. All were additionally taking oestrogen-based hormone replacement therapy (HRT). They attended for a testosterone day curve with Testogel 16.2 mg/g at the dose of 20.25 mg applied after an initial blood test. Samples were taken 2-hourly for 10 h and at 24 h post-Testogel 16.2 mg/g application. Testosterone was measured by mass spectrometry. The Female Sexual Functioning Index (FSFI) was completed by the women. Pharmacokinetic parameters of maximum concentration (Cmax), average concentration (Cavg), time to Cmax (Tmax), Area under curve (AUC) and half-life (t_1/2) were determined with and without adjustment for baseline testosterone.

Results

Mean age of the women was 53.7 ± 6.8 years, and the mean BMI was 27.4 ± 4.3 kg/m². Mean blood pressure was 126/75 mmHg. The unadjusted median Cmax testosterone concentration was 6.25 nmol/L (range 1.3−26.1), and Cavg was 4.51 nmol/L (range 0.93−20.21). AUC testosterone varied substantially from 35.9 to 458 nmol.h/L (median 121.8). The baseline-adjusted median Cmax was 3.55 nmol/L and the Cavg was 1.64 nmol/L. There was considerable variability between individuals in both measured Cmax in testosterone through the day (1.3−26.1 nmol/L) The AUC testosterone ranged from 39.45 to 181.8 nmol.h/L. FSFI median score was 26.5/36 (25%−75% interquartile range 18−30) with the highest domain scores for sexual satisfaction and arousal (4.2/6) and slightly lower scores for orgasm and desire (4.0/6), and no reported issues regarding pain on intercourse. All women subjectively reported an improvement in sexual function with Testogel 16.2 mg/g. No symptoms of hyperandrogenism were reported.

Conclusion

We found considerable variation in all parameters relating to testosterone pharmacokinetics in women applying 20.25 mg testosterone gel in a 3 or 4-day regime. All women described clinical benefit prior to the study, with no reports of androgen-related side-effects. Progression to a daily licensed topical formulation of testosterone, where this is not available, would be a positive step for women's health.