Systemic Pharmacologic Interventions

Estrogen
In the United States,  the only medication approved by the Food and
Drug Administration for the treatment of sexual dysfunction in women is   estrogen (Basson,  2006).  Systemic estrogen can decrease vasomotor symptoms and insomnia as well as dyspareunia secondary to vaginal atrophy and thus may improve sexual motivation, although this premise has not been rigorously tested (Basson, 2006). However, the use of systemic estrogen in breast cancer survivors, particularly those who had hormone-sensitive tumors, is controversial.

In a small clinical trial conducted at M.  D. Anderson,  menopausal women with a history of stage I or II breast cancer with a disease-free interval of at least 2 years (for estrogen receptor-negative tumors) or at least 10 years (for tumors with unknown estrogen receptor status) were given estrogen replacement therapy (ERT) (Vassilopoulou-Sellin et al., 2002). Of the 56 breast cancer survivors who received ERT, 30 took ERT for more than 5 years, 20 took ERT for 2-5 years, and 6 took ERT for less than 2 years.

Although ERT did not appear to compromise disease-free survival in this highly selected patient population,  the authors concluded that larger randomized trials were needed to confirm the safety of ERT in breast cancer survivors. At M. D. Anderson, we do not routinely recommend hormone replacement therapy for our breast cancer survivors.

Given that desire and orgasm are mediated by testosterone, estrogen-deficient women can experience desire and can get pleasure from masturbating or being touched.

There was no difference in sexual satisfaction between the estrogen-plus-progestin and placebo groups of the Women’s Health Initiative trial, which examined exogenous hormone use in postmenopausal women (Hays et al., 2003). However, sexual dysfunction was not a primary end point of this trial, and there is concern that the assessment tool used was inadequate (Basson, 2006).

Testosterone
Basson has reviewed the recent randomized,  controlled clinical trials that investigated the impact of testosterone supplementation on a number of outcomes,  including sexual responsiveness,  level of desire, and the number of sexually satisfying events (Lobo et al., 2003; Braunstein et al.,  2005;  Buster et al.,  2005;  Simon et al.,  2005;  Basson,  2006; Davis et al., 2006). In the five trials discussed in Basson’s review, post-menopausal women were treated with systemic estrogen therapy combined with either methyltestosterone (Lobo et al., 2003) or testosterone (Braunstein et al., 2005; Buster et al., 2005; Simon et al., 2005; Davis et al., 2006). 

When the data from the four estrogen-combined-with-testosterone trials were combined,  women receiving estrogen and testosterone reported 1.9 more sexually satisfying events per month than they had at baseline, while women receiving placebo reported 0.9 more such events (Braunstein et al., 2005; Buster et al., 2005; Simon et al., 2005; Davis et al., 2006). These trials did not address the long-term implications of the use of this combination therapy.

No safety or efficacy data are available for testosterone supplementation for estrogen-deficient women (Basson,  2006).  Not surprisingly, the use of testosterone in breast cancer survivors is controversial. At M. D. Anderson, we do not routinely prescribe testosterone therapy for our breast cancer survivors with sexual dysfunction.

Phosphodiesterase Inhibitors
Sildenafil (Viagra)  is a selective inhibitor of phosphodiesterase type 5, an enzyme responsible for degrading cyclic guanosine monophosphate in the corpus cavernosum of the penis.  By diminishing the effect of phosphodiesterase type 5, sildenafil facilitates the effect of nitric oxide during sexual stimulation: cyclic guanosine monophosphate levels increase, smooth muscle relaxes,  and blood flows into the corpus cavernosum,  producing an erection in men (Sildenafil,  2007). 

However,  in two large randomized trials of women with arousal and desire disorders, sildenafil did not improve sexual desire,  sensation,  lubrication,  or satisfaction (Basson et al., 2002). In a small laboratory-based, randomized trial, some women with genital arousal disorder appeared to respond to a single dose of sildenafil (Basson and Brotto, 2003). Clearly, further studies are needed on the safety and efficacy of these drugs in women with sexual dysfunction, including breast cancer survivors.