Antidepressant-associated sexual dysfunction in women at midlife

Selective serotonin re-uptake inhibitors (SSRIs) and serotonin noradrenaline re-uptake inhibitors (SNRIs) are commonly prescribed antidepressants in women. These treatments are associated with a high rate of female sexual dysfunction (FSD). There is a concern that emergence of sexual dysfunction in women treated with SSRI/SNRIs contributes to treatment discontinuation and relapse of depression. Evidence-based data to guide the treatment for SSRI/SNRI-associated FSD is sparse, leaving clinicians uncertain as to how to manage this condition effectively and patients susceptible to unproven pharmacological approaches. The overall aim of this thesis was to investigate transdermal testosterone as a treatment option for antidepressant-emergent FSD. Accordingly, the background literature in this area was reviewed and then three original studies were conducted. I found that the current management strategies for SSRI/SNRI-associated FSD are limited, with a lack of evidence for the efficacy of transdermal testosterone in this clinical population. Therefore, I examined the efficacy of transdermal testosterone therapy for antidepressant-emergent loss of libido in women at midlife in a randomised, double-blind, placebo-controlled trial. 44 women, aged 35 to 55 years, with antidepressant-emergent loss of libido were randomly allocated to treatment with a testosterone patch delivering 300 mcg of testosterone/day or an identical placebo patch for 12 weeks. The primary outcome was the change in sexual function over 12 weeks assessed by the Sabbatsberg Sexual Self-rating Scale (SSS). The 4-week frequency of satisfactory sexual events (SSEs), sexual distress, general wellbeing, depression and mood states were also measured. Testosterone therapy resulted in a significant increase in the number of SSEs compared with placebo therapy. The effect of testosterone therapy on distress associated with low desire approached statistical significance. There was no treatment effect seen for general wellbeing, mood or depression. The lack of improvement in the SSS total score reflects lack of sensitivity of this instrument for the measurement of change in sexual function. This study provides the first evidence that testosterone therapy may be a treatment option for women with SSRI/SNRI-emergent loss of libido. As the testosterone patch used in the RCT is no longer commercially available, I investigated the pharmacokinetic profile of an available 1% transdermal testosterone cream (TTC). Healthy naturally postmenopausal women were randomly allocated to the order of treatment with 5 mg or 10 mg of the TTC to the upper arm for each of two study periods in a cross-over design. The pharmacokinetic analysis showed the 5-mg dose restores total testosterone levels to above, and free testosterone levels to within the normal range for premenopausal women. This formulation would appear a suitable option for the treatment of women when testosterone therapy is indicated. My third study was undertaken to elucidate women’s expectations of medical treatment for sexual dysfunction and their self-appraisal of treatment outcomes utilising a qualitative approach. Women referred to an endocrinologist for their sexual difficulties were interviewed before and after their medical consultation. The themes that emerged from this study were that women had 1) personal psychological distress associated with FSD, (2) concerned about the negative effect of sexual dysfunction on the relationship with their sexual partner, (3) a belief in a relationship between sexual dysfunction and “hormone deficiency”, and (4) an expectation of treatment, which included positive physical and sexual changes. Several conclusions can be drawn from this thesis. Women presenting for treatment of sexual dysfunction are distressed about their sexual problem, concerned about the negative impact of their sexual difficulties on their relationship and are hopeful that they will be offered a treatment for their problem which could bring about physical and sexual changes. Transdermal testosterone improves sexual function in women with SSRI/SNRI-emergent libido disorder and a 5mg dose of a 1% TTC provides a therapeutic option for women seeking treatment.