AUA Summit - Sexual Dysfunction

Sexual Dysfunction

Out of the Darkness: Sexual Dysfunction Disorders Enter Public Spotlight

Urologists are leading the march as sexual medicine moves into the next century. After all, few physicians are as adept at carrying the flag for our most intimate issues as those already treating our most private conditions.

But, despite the vast inroads made in the field of sexual dysfunction in recent years, it took the better part of a century before doctors of any stripe stepped up to deal with the condition—in either gender. Today, urologists are behind a scientific explosion in the field as it relates to both male and female sexual dysfunction.

Long left to believe sexual problems were psychological, women have seen a rapid turn of events in recent years as doctors investigate the issue: There's now proof that the arousal-to-orgasm miscues some women experience can originate in their bodies, not just in their heads. Not since William Masters and Virginia Johnson described vaginal changes during sexual arousal in 1966 has so much attention been paid to female physiology as it relates to sexual function, or the lack thereof.

In 1997, more than 30 years after Masters and Johnson published their groundbreaking book, Human Sexual Response, Boston University's Kwangsung Park suggested that diminished blood flow reduced arousal in the clitoris and vagina, just as it did in the penis. With animal models, he was the first to show that a woman's problems could be physiological.

The lack of consensus on definitions of what female sexual dysfunction was clinically and the fact that psychologists and physicians had been working independently up to that point laid the ground for a 1998 international meeting that delivered a roadmap for female sexual dysfunction. For the first time, a multi-disciplinary panel sponsored by the American Foundation for Urologic Disease standardized existing disorders of sexual arousal, desire, orgasm and pain for women, confirming that they could be triggered by physiological and psychological causes—the need for additional research in the area.

Yet, despite the accelerated pace in recent years, research on female sexual dysfunction still lags behind that of men, who, for centuries have taken desperate measures to recapture their sexual vigor. While "lost manhood" charlatans of the early 1900s hawked bogus testicular rejuvenation extracts, physicians attempted to "renew" patients by grafting human cadaver testicles into them.

Though these treatments failed, they did succeed in energizing Texas surgeon J.S. Wooten (1902) and Illinois professor G.F. Lydston (1908) who conducted the first penile surgeries by tying off blood vessels to cause engorgement. Later, N.A. Bogoras (1936) and R.T. Bergman (1948) inserted rib cartilege for rigidity.

The heroes behind the modern penile prosthesis were urologists who fashioned the first successful inflatable penile prosthesis. By 1973, F. Bradley Scott and his Houston colleagues had succeeded in implanting a device into the penis that could be pumped with saline to achieve erection. Shortly thereafter, urologists Michael Small and Hernan Carrion introduced an implantable, "malleable" rigid rod as a prosthesis. While others added silver wire and hinges, these models were the prototypes of today's prostheses.

But the introduction of the penile prosthesis paled in comparison to British physiologist Giles Brindley's dramatic demonstration at the 1983 Annual Meeting of the AUA. Brindley closed his lecture by dropping his pants to reveal a perfectly-erect phenoxybenzamine-induced erection. Following Brindley's lecture demonstration, Adrian Zorgniotti began teaching patients self-injections with injectable phentolamine and papaverine, a drug touted in 1982 by French vascular surgeon Ronald Virag. In the meantime, two functional tests for penile circulation were developed: one was a duplex ultrasound test by Tom F. Lue at the University of California, San Francisco and the other was dynamic cavernosometry and cavernosography by Irwin Goldstein at Boston University.

By the mid- to late 1980s, patients would have their first self-injectable impotence drug, with FDA-approved alprostadil (prostaglandin-E1). Thereafter, physicians often prescribed a "triple-mix" of vasoactive drugs—papaverine, prostaglandin, and phentolamine. By 1997, an innovative applicator—MUSE (Medicated Urethral System for Erection)—to facilitate prostaglandin absorption by the urethral mucosa was approved by the FDA.

But, while these prostheses and pharmaceutical aids were helpful for men suffering from erectile dysfunction, they did not compare to the ease of orally administered sildenafil citrate, a cardiovascular dilating agent used for patients with angina. British scientists noted its penis-enhancing capabilities when study participants reported erections. Sildenafil citrate, with the proprietary name of Viagra, caught on like wildfire in the late 1990s, even before Sen. Bob Dole became a spokesperson for the drug. But Viagra's benefits may not be limited solely to males: evidence has suggested that it could also increase genital blood flow in females. Since the advent of sildenafil citrate, other drugs—vardenafil, tadalafil, and avanafil—have also entered the erectile dysfunction arena.

And research continues as physicians work to unravel the secrets to sexuality. Lue, along with Goldstein, already have confirmed the role of arterial flow and relaxed penile smooth muscle in achieving erections. Moreover, at the University of California, Los Angeles, Jacob Rajfer and Louis Ignarro (a Nobel laureate) identified nitric oxide as the principal neurotransmitter for penile erection.

With these advancements, science is turning away towards mitigating ED, and working towards therapies that can restore and regenerate erectile tissues. These include the use of low-intensity shock wave therapy (LiSWT), intracavernous stem cell therapy (SCT), intracavernous platelet rich plasma (PRP) therapy (and other agents such as amniotic fluid) platelet rich plasma (PRP) injections.

Yoram Vardi reported the first study evaluating Li-SWT for erectile dysfunction (2010) and showed clinically meaningful improvements in IIEF scores. Since then there have been over 16 clinical trials, of which 7 were randomized controlled trials all assessing the efficacy of Li-SWT for ED. In systematic reviews, positive results suggest that LiSWT may play a role in the future treatment of ED and be a paradigm changer in how erectile function is treated. Unfortunately for PRP, the results are few and lacking, and there exists no human data evaluating PRP as regenerative therapy for ED.

Due to the popularity of these therapies and the paucity of robust data surrounding their efficacy and safety, the Sexual Medicine Society of North America (SMSNA) issued a statement that the use of shock waves, stem cells or PRP is experimental and should be conducted under research protocols in compliance with Institutional Review Board approval. Finally, the SMSNA advocated that patients involved in these clinical trials should not incur more than basic research costs for their participation. As science continues to define new treatments for preserving and regenerating erectile tissue, the future awaits, eagerly.

Back on the female side, UCLA urologist Jennifer Berman, along with her sister, sex therapist Laura Berman, started a trend with female sexual medicine investigating the hormones that promote female sexual function and response—and the medical conditions that prevent it. In 2000, the FDA approved the first female clitoral therapy device, the EROS. When the handheld clitoral therapy device was turned on, a small cup placed on the clitoris created a gentle vacuum, increasing blood flow and thus engorgement to the clitoris to help promote an enhanced ability to achieve orgasm.

Until August 2015, there were no other widely available treatment options for female sexual dysfunction until the FDA approved the first ever "female viagra" otherwise known as Addyi (flibanserin) which was the first prescription treatment available for premenopausal women with low libido or reduced sex-drive. Originally used as an antidepressant, the new brand name drug, produced by Sprout pharmaceuticals, garnered attention everywhere for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD). Women all over sang praises.

Vyleesi (bremelanotide), hit the market next as the second FDA approved medication for premenopausal women with hypoactive sexual desire disorder (HSDD) in June 2019. A melanocortin receptor agonist, it is self-administered into a woman's abdomen or thigh via a prefilled autoinjector pen 45 minutes before anticipated sexual activity. It could be administered at any time of day and unlike Addyi did not come with an alcohol ban.

While neither medication is the silver bullet for female sexual dysfunction, they are driving a newly ignited focus and attention to a previously understudied and unmet need.

These developments are just an inkling of things to come as urology's most prolific thinkers carry sexual medicine's flag into the next century.

Rainer Engel, MD
Helen Levey Bernie, MD