Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.

Erectile dysfunction (previously called impotence) is the inability to get or maintain an erection that is sufficient to ensure satisfactory sex for both partners. This problem can cause significant distress for couples. Fortunately more and more men of all ages are seeking help, and treatment for ED has advanced rapidly. The enormous demand for “anti-impotence” drugs suggests that erection problems may be more common than was previously thought. Find out more about the causes and treatment of erectile dysfunction here.
^ Jump up to: a b Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A (2011). "Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis". PLoS Biol. 9 (4): e1001051. doi:10.1371/journal.pbio.1001051. PMC 3082517. PMID 21541365.
Impotence is a common problem among men and is characterized by the consistent inability to sustain an erection sufficient for sexual intercourse or the inability to achieve ejaculation, or both. Erectile dysfunction can vary. It can involve a total inability to achieve an erection or ejaculation, an inconsistent ability to do so, or a tendency to sustain only very brief erections.

However, a review of a United Kingdom medical record database found no evidence that the use of 5-alpha reductase inhibitors independently increase the risk for ED. In 71,849 men with benign prostatic hyperplasia (BPH), the risk of ED was not increased with the use of finasteride or dutasteride only (odds ratio [OR] 0.94), or a 5-alpha reductase inhibitor plus an alpha blocker (OR 0.92) compared with an alpha blocker only. In addition, the risk of ED was not increase in 12 346 men prescribed finasteride 1 mg for alopecia, compared with unexposed men with alopecia (OR 0.95). The risk of ED did increase with longer duration of BPH, regardless of drug exposure. [48]


The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
The FDA recommends that men follow general precautions before taking a medication for ED. Men who are taking medications that contain nitrates, such as nitroglycerin, should NOT use these medications. Taking nitrates with one of these medications can lower blood pressure too much. In addition, men who take tadalafil or vardenfil should use alpha blockers with care and only as instructed by their physician, as they could result in hypotension (abnormally low blood pressure). Experts recommend that men have a complete medical history and physical examination to determine the cause of ED. Men should tell their doctor about all the medications they are taking, including over-the-counter medications.
Dr. Wassersug, whose background is in evolutionary biology, also noted that lower testosterone in older men may be adaptive, a positive benefit, as our bodies age and become increasingly frail. "The argument can be made," he said, "that it's not beneficial to have the mindset of a 19-year-old when you are 49-years-old, because if you are aggressive enough to get into a conflict with an actual 19-year-old, you are going to get killed."
In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6.[151] 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.[151] The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism.[151] In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites.[151][152] Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.[151]
The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. [10]

Chronic stress dumps adrenaline in your system multiple times a day. And that can lead to high blood pressure, heart disease, obesity, and diabetes. Chronic stress is like red-lining your car all day long. When you drive 100 mph all the time, something is going to break down. A high-stress environment can actually change the way your brain sends messages to your body. Dumping too much adrenaline into your bloodstream can affect blood flow and severely limit your ability to achieve and maintain an erection.

"The hard part," said Dr. Anawalt, "is the man who is 50 pounds overweight and sedentary, who sees a TV ad and goes to see his doctor. Let's say he has a thoughtful doctor who does the right test, at the right time of day (morning), and the test comes back low. Many of these guys will have low or slightly low testosterone. We have no evidence for whether or not it's a benefit to give these guys testosterone." He added that concern about their testosterone level could be a good thing if it spurs men to lose weight and exercise. "A low testosterone level can be a marker of poor health," he said.

A physical cause can be identified in about 80% of cases.[1] These include cardiovascular disease, diabetes mellitus, neurological problems such as following prostatectomy, hypogonadism, and drug side effects. Psychological impotence is where erection or penetration fails due to thoughts or feelings; this is somewhat less frequent, in the order of about 10% of cases.[1] In psychological impotence, there is a strong response to placebo treatment.
Once a complete sexual and medical history has been completed, appropriate laboratory studies should be conducted. In the initial evaluation of ED, sophisticated laboratory testing is rarely necessary. For example, serum testosterone (and sometimes prolactin) is typically only useful when the patient demonstrates hypogonadal features or testicular atrophy, or when clinical history is suggestive. Additional hormonal evaluation may include thyroid stimulating hormone in those with a clinical suspicion of hypothyroidism or appropriate diabetes screening in those presenting with a concern for impaired glucose metabolism. If the patient has not been evaluated with a lipid panel and hyperlipidemia is suspected, measurement and appropriate referral to internal medicine or cardiology is recommended. In most cases, a tentative diagnosis can be established with a complete sexual and medical history, physical examination, and limited or no laboratory testing.
Like other steroid hormones, testosterone is derived from cholesterol (see figure).[120] The first step in the biosynthesis involves the oxidative cleavage of the side-chain of cholesterol by cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), a mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A1 (17α-hydroxylase/17,20-lyase) enzyme in the endoplasmic reticulum to yield a variety of C19 steroids.[121] In addition, the 3β-hydroxyl group is oxidized by 3β-hydroxysteroid dehydrogenase to produce androstenedione. In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield testosterone.

An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defining the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specific nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefit. The traditional benefits of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible beneficial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations.

Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.


Think of erectile dysfunction as your body’s “check engine light.” The blood vessels in the penis are smaller than other parts of the body, so underlying conditions like blocked arteries, heart disease, or high blood pressure usually show up as ED before something more serious like a heart attack or stroke. ED is your body’s way of saying, “Something is wrong.” And the list of things that cause erectile dysfunction can include:
Diabetes is an example of an endocrine disease that can cause a person to experience impotence. Diabetes affects the body’s ability to utilize the hormone insulin. One of the side effects associated with chronic diabetes is nerve damage. This affects penis sensations. Other complications associated with diabetes are impaired blood flow and hormone levels. Both of these factors can contribute to impotence.
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