(40) Life after Breast Cancer

What is Apomorphine?

Apomorphine has been used sublingually for the treatment of male sexual health concerns. It is sometimes considered an alternative to the phosphodiesterase inhibitors. In a Journal of Sexual Medicine article, Bechara and associates published an excellent, although small, study titled “A Double Blind Randomized Placebo Control Study Comparing the Objective and Subjective Changes in Female Sexual Response Using Sublingual Apomorphine.”

This attempted to show the effect of 3 mg of apomorphine in the female response cycle in those women who were diagnosed with orgasmic problems. This study demonstrates that clitoral blood flow changes in peak velocity were significantly higher in the subjects who took the medication, which theoretically translates into better pelvic blood flow. This phenomenon, when considered in a broader light, would mean changes in arousal and lubrication. These areas were also significantly improved in the Apomorphine group.

The researchers concluded that this medication was beneficial for women with orgasmic problems or complaints. They also propose an anatomic mechanistic model of the function and result of the drug. The side effects and adverse events were low in incidence and were mostly mild and transient. Although this study involved very small numbers, many sexual healthcare professionals are optimistic because the medication is provocative and warrants further rigorous study for the treatment of female sexual complaints. It is not presently available for prescription to female sexual health patients, but studies are ongoing.

How can the antidepressant bupropion (Wellbutrin) be helpful to my sexual health?

Bupropion, or Wellbutrin (GlaxoSmithKline), is a nonserotonin reuptake inhibitor antidepressant (medication that has recently been touted as having the least sexual side effects). This medication is a weak blocker of the uptake of the brain chemicals serotonin and norepinephrine and is commonly used in smoking cessation programs. Some patients on this medication report an increase in sexual desire. A typical trial of this medication includes a starting dose of 75 mg that can be increased gradually. Precautions and possible side effects include insomnia, nervousness, and mild to moderate increases in blood pressure, as well as a risk of lowering seizure threshold.

Drs. Seagraves and Clayton published a study titled “Bupropion Sustained Release for the Treatment of Hypoactive Sexual Desire in Premenopausal Women” in the Journal of Clinical Psychopharmacology. This landmark study examined women with hypoactive sexual desire disorder in a randomized placebo-controlled trial with increasing doses of bupropion. All measures indicated increased sexual responsiveness and increased sexual arousal, orgasmic completion, and overall sexual satisfaction. The researchers propose a mechanism by which the medication operates and causes positive sexual effects by acting on the dopamine and norepinephrine pathways.

There are minimal side effects, and most women can tolerate this medication. It has been used extensively by sexual medicine healthcare provider’s off-label for complaints of low desire and lowered libido.

What is Flibanserin?

Flibanserin is a 5-HT1A agonist/5-HT2 antagonist. It is manufactured by a private German company called Boehringer Ingelheim and was initially produced as an antidepressant medication. In the late 1990s, the company developed a molecule called Flibanserin that seemed to relieve stress in rats. Unfortunately, this medication did not do well as an antidepressant. Its half-life is approximately 7 hours and appears to be safe with minimal interactions with other medications. Flibanserin shows excellent promise for treatment of hypoactive sexual desire disorder in women. Recently in Europe, data showed the results from the premenopausal trials that reiterated excellent tolerance, a low side effect profile, and increased satisfying sexual events for those women who took the medication. Few withdrew from the study, and many were very satisfied with the results. Ongoing trials are underway for the postmenopausal group. The dose was 100 mg taken at nighttime and showed to decrease distress associated with lowered sexual desire. Side effects were transient and mild. Because this medication is not a hormone, it can hopefully be used for women who have breast cancer. The medication has now completed stage 3 clinical trials, and many sexual healthcare providers assume effectiveness with minimal side effects. This medication acts centrally, and some of the mild side effects include somnolence fatigue, and sleeplessness. Unfortunately, although the mechanism of how Flibanserin has yet to be clarified, it may modulate several circuits in the brain that may be linked to feelings of enjoyment and pleasure. It may act as a serotonin modulator that restores the balance of this compound. It may restore hormonal balance. According to the company’s spokesperson, one of those brain circuits apparently helps control sexual desire and arousal. The effects of the drugs are not immediate and may take some time to occur. Recently, data from the Rose study, an open label randomized withdrawal study, were presented in Europe and demonstrated increased desire days and increased satisfying sexual events for women on this medication. Boehringer Ingelheim has placed a large investment in this medication. The company launched four major clinical trials, involving 5,000 women in 220 worldwide locations, with the goal of applying approval shortly. Sexual healthcare providers are eagerly awaiting the news of a potential treatment for female hypoactive sexual desire disorder. Flibanserin was featured in an issue of Business Week and gained notoriety as the most plausible treatment for hypoactive sexual desire disorder-a first for women’s sexual complaints! There is also a company-sponsored disease registry that will follow many women with Hypoactive Sexual Desire Disorder (HSDD) or troublesome lowered sexual libido over the course of several years. The Southern California Center for Sexual Health and Survivorship Medicine in Newport Beach and the Institute for Pelvic Pain in Philadelphia were chosen as premier vanguard sites. Eligible participants may enroll after the informed consent procedure and are entitled to remuneration.

What is Tibolone?

Tibolone (Livial) is a synthetic hormone-type drug. Livial has been found to increase the risk of recurrence in a randomized trial for patients with breast cancer (particularly if estrogen receptor positive). It is used mainly for hormone therapy in postmenopausal women. Tibolone can help relieve symptoms of the menopause transition, including hot flashes, night sweats, mood changes, vaginal dryness, and vaginal irritation. It can also help to prevent bone health issues such as osteoporosis. Many studies over the last 5 years show that Tibolone, a new female hormone, shares many effects with male hormones and may prevent bone problems and lack of sexual desire. Tibolone’s cardiovascular effects are much less clear. On the positive side, the drug reduces total cholesterol and harmful triglycerides and slightly lowers low-density lipoproteins (bad cholesterol), but it also lowers high-density lipoproteins (good cholesterol).

Many experts are concerned about this mixed picture toward cardiovascular health. Tibolone (Livial) is available in much of continental Europe and the United Kingdom, but it is not yet available in the United States. The drug may improve desire, but researchers are uncertain of its effect on other parameters of female sexual function. This medication may not be a viable option for women who have breast cancer.

What is Bremelanotide?

PT-141 (Bremelanotide) is a melanocortin receptor agonist that was under study and development for the treatment of both male and female sexual complaints. Originally, this medication was developed and tested as a sunless tanning agent but was not effective; however, some subjects reported increased sexual arousal and spontaneous erections. Some serious concerns regarding the benefit and risk ratio of Bremelanotide caused delay in the stage 3 clinical trial regarding some severe changes in blood pressure. The melanocortins are thought to play an important role in female sexual health and functioning. The medication, which was under study and in advanced clinical trials, is a centrally acting drug that can affect the brain. It is a colorless, odorless chemical that is placed within a nasal inhaler and has been used by many women with sexual complaints. Some women who have taken this medication have reported increased warmth or throbbing in the genitals as well as an increased desire to engage in intercourse. A phase 2A pilot clinical study looked at this medication in premenopausal women diagnosed with female sexual dysfunction, and it has not shown encouraging results.

On May 13, 2008, Palatin Technologies, the maker of Bremelanotide, announced that it had discontinued further development of Bremelanotide for the treatment of both male and female sexual dysfunction; however, the company is researching a new compound, PL-6983, that causes significantly lower increases in blood pressure than those seen with Bremelanotide in animal models. There is hope in the future; we should await further studies and publications. In preliminary studies it has shown to increase sexual activity.

Terms:

Dopamine – A catecholamine that serves as a neurotransmitter and also as a hormone inhibiting the release of prolactin from the anterior portion of the pituitary gland. It is involved in the neurochemistry of sexual function for both men and women.

Norepinephrine – A catecholamine with dual roles as a hormone and a neurotransmitter.

Hormone therapy – The use of medications to modify or replace those whose production is decreased or absent in the menopause period.