MALE SEXUAL DYSFUNCTION INCIDENCE Somewhere around 1/3rd of US males Incidence increases rapidly with age over 40 With 25% of the 40-49 yr group perceiving a problem RISK FACTORS Psychosomatic factors - worry, anxiety about performance the largest single factor Accounts for between a third and one-half of all disorders Easily diagnosed: nocturnal erections are normal Circulatory problems - major cause of true physiological erectile dysfunction Obesity - not a direct cause, but contributes via effects on the cardiovascular system Diabetes Depression - linked to lowered libido Endocrine disorders: Abnormally low T Hyperprolactinemia FEMALE SEXUAL DYSFUNCTION WE HAVE BARELY BEGUN TO STUDY THIS TOPIC Used to be called frigidity Was, still is often the practice to discourage female sexuality "Nice girls don't" "Close your eyes and think of England" Societal panic about "children" and "pornography" somehow always seems to selectively involve girls + Full male nudity still much rarer than female nudity in film, art Female virginity - until quite recently, brides blushed because they were expected to be sexually naive And there was wide-spread attention paid to hymens, "maidenheads", "deflowering" Sometimes accompanied by public display of blood on the bedding after the "wedding night" Not surprisingly, until about 2 days ago, little research into female sexual problems Compounded by the fact that the female sexual response is psychologically more complex than male arousal INCIDENCE Uncertain but high, certainly higher than male problems Maybe over 40% (???) Includes mechanical problems such as dryness, vaginal pain More often problems with libido, failure to achieve orgasm Traditionally attributed to problems in context and relationships, but who knows?? RISK FACTORS Very much like male risk factors, including: Age Depression PHARMACOLOGICAL TREATMENT OF MALE SEXUAL DYSFUNCTION PLACEBO EFFECTS Since such problems are often psychogenic, there are BIIG placebo effects VIAGRA Mechanism: Inhibits the enzyme (phosphodiesterase type 5) which metabolizes the cGMP released in penile smooth muscle by NO Generic name Sildenafil citrate Investigated by Pfizer as a blood pressure control medication, found to improve erectile function Efficacy: Substantial; at 100 mg over 80% of males with problems report success, vs 25% in the placebo group NOTE - Viagra is NOT an aphrodisiac, does not directly enhance NO release or libido + Psychologically, of course, this is a very different matter! Pharmacokinetics: Half-life around 4 hrs, cMax around 1 hr + Hence substantial delay between oral administration and efficacy Metabolized by hepatic P450s Side effects: Headaches, slight lowering of blood pressure, mild stomach upset and visual effects Potentially lethal if taken with NO releasers Numerous post-marketing reports of cardiac death + But is it the sexual activity or the drug which kills? PROSTAGLANDINS Play a secondary role in relaxing penile smooth musculature PGE1 is the active form Administered either as an intraurethral suppository OR directly injected into the corpora cavernosa bilaterally Popularity low post-viagra ADRENERGICS Alpha 1 and 2 blockers also prevent loss of erection Often administered by penile injection Again, not terribly popular after Viagra UPRIMA Claimed to work directly on mesolimbic DA system input to the MPOA Not yet on market, but much media attention Dissolved under tongue, studies found effective in 47% of patients, vs "only" 33% on placebo Side effects - decreased blood pressure, sometimes fainting sometimes while driving! FDA panelist says it WILL kill people, but hey, we gotta have it! TESTOSTERONE - replacement therapy poorly studied, and none too promising THE INVISIBLE OTHER HALF OF THE EQUATION For every guy taking such medications, there is presumably a female partner involved Drug literature paints these women as deeply, profoundly gratified at the "restoration" of function Of course no one has bothered to ask women about their attitudes to pharmacological enhancement of the male sexual response! PHARMACOLOGICAL TREATMENT OF FEMALE SEXUAL DYSFUNCTION VIAGRA Pfizer is about to market a viagra cream, to be applied to the clitoris Is failure of clitoral erection a major female sexual problem? Who knows? Will the cream sell well? You betcha! TESTOSTERONE Strong indications that post-menopausal women benefit from androgen replacement therapy SUPPOSEDLY at levels below that required to grow moustaches! But topic still very poorly researched - of course NOT because of lack of proprietary patents! APHRODISIACS: DRUGS WHICH ENHANCE SEXUAL AROUSAL YOHIMBINE Found in some plants, including the bark of a West African tree Sold without prescription as Yohimbe Also available by prescription An alpha-2 blocker And hence indirectly a norepi releaser Can be expected to reduce the duration of the male refractory period So could be a type of aphrodisiac Effects on male rats - does just that, restores "sexually exhausted" males to action Human use: A lot of "street buzz" about the aphrodisiac properties of this compound A testimonial from the internet: "Furthermore, the real promise of yohimbe actually is not its value as medication of erectile dysfunction in men who indeed suffer from the condition but its power to enhance sexuality in healthy subjects. Yohimbe is probably the most underrated recreational drugs around. It's not just a sex enhancer; it's a philosophical life enhancer. It has the clear potential to give new meaning to the lives of men at mid-life and beyond. Yohimbe restores pride and enjoyment. For performance and sheer manhood, men at 50 who have ingested yohimbe can compete with any young gigolo. Forget such esoteric nonsense as tantra yoga and the tao of love. All you need is yohimbe. " (and just maybe a partner???) Side-effects: Alpha-2 blockade lowers blood pressure, causes orthostatic hypotension + So could interact badly with either Uprima or Viagra High doses are hallucinogenic and can trigger severe anxiety Yohimbine does not appear to do anything for women (???) DOPAMINE AGONISTS Include amphetamines, cocaine, receptor agonists such as apomorphine Clearly such compounds enhance libido In both sexes AND in lab animals Note that Parkinson's accompanied by lowered libido, while L-Dopa can cause hypersexuality Side effects: Obvious stuff such as addiction, STDs, paranoia, getting busted Less obviously, heavy long-term cocaine use causes male impotence + possible norepi mechanism "POPPERS" - AMYL NITRATE AND RELATED DRUGS Inhalants, used to block angina by releasing NO Also used by homosexuals to enhance orgasm Doubtlessly a VERY bad idea if taken with Viagra! GABA AGONISTS All are anxiolytics, which may cause a lowering of inhibitions Not to mention anesthesia, which certainly lowers resistance! Alcohol "Candy's dandy, but liquor's quicker" Despite anxiolytic properties, all such compounds actually REDUCE libido DRUGS WHICH IMPAIR SEXUAL AROUSAL A NUMBER OF NEUROTRANSMITTER SYSTEMS SUPPRESS SEX Opiates Serotonin GABA AS DO A VARIETY OF PSYCHOACTIVE COMPOUNDS Such effects largely ignored Many of the disease states repress libido SSRIs, other antidepressants A definite result of serotonin release Neuroleptics; through several mechanisms Dopamine antagonists Prolactin releasers