ERECTILE DYSFUNCTION Harvard-MIT Division of Health Sciences and TechnologyHST.071: Human Reproductive BiologyERECTILE DYSFUNCTION Puncturing one's penis with a needle is not for the squeamish. Piercing the penis with a needle and then injecting a chemical to enhance one's sexual potency sounds more like a bizarre, sadomasochistic nightmare from the annals of Krafft-Ebing's Psychopathia Sexualis than a doctor-recommended treatment of impotence. Nevertheless, many men, with guidance from their physicians, practice self-injection of the penis to achieve an erection. Three types of medications – phentolamine (an alpha-blocker), papaverine (a smooth muscle blocker)- and prostaglandin E1-are used. These medications are effective in stimulating erections because they overcome neurologic signals that normally keep the penis in a limp or flaccid state. Neurological control of erections is vested in the sympathetic nervous system. To understand how the sympathetic nervous system works, it is useful to create a simple scary example. Imagine, that you are alone at night walking down a dark street. There is no sound. Then, as you are absorbed with your thoughts, someone sneaks up behind you and says, "Boo!" Your sympathetic nervous system immediately swings into action to cause, among other reactions, an increase in pulse rate and blood pressure. The change in pulse and blood pres- sure is caused by internally produced adrenaline like compounds with unique properties designated alpha or beta. Beta forces cause an increase in pulse rate, while alpha influences are responsible for the increase in blood pressure. What does this have to do with erections? The penis is richly endowed with extensions of the sympathetic nervous system, specifically nerves of the alpha type. Alpha influences play a vital role as facilitators or inhibitors of normal erections. When the alpha forces dominate, the penis remains at rest. A penile injection of a medication that blocks the alpha nerves overrides these influences and makes it possible for a full and unrestrained flow of blood to be directed into the erectile bodies of the penis. Medications like phentolamine, an alpha blocker, and prostaglandin E, a muscle relaxant with probable alpha-blocking activity, cause erections by interfering with the prevailing nerve signals that would maintain the penis in a limp state. It is somewhat more difficult to understand exactly how papaverine works. There are no papaverine receptors in the penis. Papaverine, unlike alpha-adrenergic compounds or prostaglandins, is not made by the body. However, papaverine has one characteristic that is useful in inducing an erection: It is a smooth-muscle relaxant. The body has two types of muscles, striated and smooth. Striated muscles are literally striped in appearance and are, for the most part, under voluntary control. The muscles of the arms, legs, and face are striated muscles. Smooth muscle~ are not under volitional control. For example, the muscles in the intestines are smooth muscles. The muscles lining the penile blood vessels that must dilate for an erection to occur are also smooth muscles. It is presumed that papaverine induces an erection by causing these intrapenile smooth muscles to relax, thereby allowing or encouraging increased blood flow into the penis. Penile InjectionTo be fully effective, the medications must be injected directly into one of the penile erectile bodies, the corpora cavernosum. The medication will diffuse over to the other side of the penis so that symmetrical erection is acquired.) Method of intrapenile injection. A cross section of the penis illustrates the corpora cavernosa surrounded by the thick outer fibrous sheath (tunica. albuginea) .The needle is inserted at a ninety-degree angle to the penile shaft and must penetrate the tunica albuginea to make contact with the corpus cavernosum. Patients are taught to advance the needle into the penis and wait for a slight "give" in the resistance. When they sense this change in tension, they know that they have punctured the tunica albuginea. The medicine is then injected. An erection occurs within ten to thirty minutes. Most urologists recommend that injection be performed no more than twice a week. Papaverine, phentolamine, and prostaglandin E, (marketed as alprostadil [Prostin VR Pediatric]) are available in most phar- macies, as are insulin syringes with very small needles. Candidates for Intrapenile Injections Sixty-five to 75 percent of impotent men can have an erection induced by the intrapenile injection of combined papaverine and phentolamine. Preliminary reports from Japan suggest that 86 percent acquire erections with prostaglandin E, alone. The men most likely to respond to injections are those with neurogenic impotence. Injection can induce erections in men with vasculogenic impotence, but only if the dose of medication is significantly greater than that needed for other men. Intrapenile injections are not an effective long-term treatment for men with vasculogenic impotence because the injections will eventually fail to stimulate erections even if a large amount of drug is used. In addition, for reasons that remain unclear, about one-third of men with psychogenic impotence do not respond adequately to intrapenile injections.Yohimbine Man has always been intrigued and tantalized by the fantasy of discovering an aphrodisiac, a substance that would stimulate his sexual appetite and power. Some foods and drugs are thought to be imbued with aphrodisiac properties, and those who were privy to the secret ingredients of the sexually stimulating substances were highly valued. The physician to Louis XIV slipped the monarch a special potion each night before the king received a new lady in his bedchambers. The royal physician's potions were not always effective, causing the king to become displeased, truculent, and vengeful. At one time it was believed that the drug yohimbine had aphrodisiac properties. Certainly yohimbine had the appropriately exotic lineage to satisfy preconceptions of what an aphrodisiac should be. Yohimbine was derived from the bark of a tree that grows only in Africa. It was believed that natives boiled the tree bark in a caldron and then harvested the residue. The yohimbine extract was then administered to men and women who were said to experience a sudden and striking increase in sexual desire.