The brain is also affected by this sexual differentiation;[13] the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with congenital diseases of androgen formation or androgen receptor function, to be associated with functional androgen receptors.[95]

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Although vardenafil does not seem to produce significant clinical QT prolongation, it has been suggested that it be avoided in patients who have congenital QT prolongation abnormalities and in patients using class I antiarrhythmic drugs, such as quinidine and procainamide. It is also best to avoid the use of vardenafil with class III antiarrhythmic drugs, such as amiodarone or sotalol.
Oral/buccal (by mouth). The buccal dose comes in a patch that you place above your incisor (canine or "eyetooth"). The medication looks like a tablet but you should not chew or swallow it. The drug is released over 12 hours. This method has fewer harmful side effects on the liver than if the drug is swallowed, but it may cause headaches or cause irritation where you place it.

It is essential to discuss erectile dysfunction with your doctor, so any serious underlying causes can be excluded and treatment options can be discussed. Many men are embarrassed discussing this issue with their doctor, or even their partner. Open communication with your doctor, and in your relationship, is important for effectively managing this common problem.

Cognitive abilities differ between males and females and these differences are present from childhood. In broad terms, girls have stronger verbal skills than boys who tend to have stronger skills related to spatial ability (Linn and Petersen 1985). It is thought that the actions of sex hormones have a role in these differences. Reviewing different cognitive strengths of male versus female humans is not within the scope of this article but the idea that cognition could be altered by testosterone deserves attention.
early 15c., "physical weakness," also "poverty," from Middle French impotence "weakness," from Latin impotentia "lack of control or power," from impotentem (nominative impotens); see impotent. In reference to a want of (male) sexual potency, from c.1500. The figurative senses of the word in Latin were "violence, fury, unbridled passion." Related: Impotency.
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Studies of the effects on cognition of testosterone treatment in non-cognitively impaired eugonadal and hypogonadal ageing males have shown varying results, with some showing beneficial effects on spatial cognition (Janowsky et al 1994; Cherrier et al 2001), verbal memory (Cherrier et al 2001) and working memory (Janowsky et al 2000), and others showing no effects (Sih et al 1997; Kenny et al 2002). Other trials have examined the effects of testosterone treatment in older men with Alzheimer’s disease or cognitive decline. Results have been promising, with two studies showing beneficial effects of testosterone treatment on spatial and verbal memory (Cherrier et al 2005b) and cognitive assessments including visual-spatial memory (Tan and Pu 2003), and a recent randomized controlled trial comparing placebo versus testosterone versus testosterone and an aromatase inhibitor suggesting that testosterone treatment improves spatial memory directly and verbal memory after conversion to estrogen (Cherrier et al 2005a). Not all studies have shown positive results (Kenny et al 2004; Lu et al 2005), and variations could be due to the different measures of cognitive abilities that were used and the cognitive state of men at baseline. The data from clinical trials offers evidence that testosterone may be beneficial for certain elements of cognitive function in the aging male with or without cognitive decline. Larger studies are needed to confirm and clarify these effects.
Erectile dysfunction may be an unpleasant condition that no one really wants to talk about, failing to acknowledge it won’t make the problem go away. Your best defense against health problems like this is to learn everything you can about it so you can tackle the problem at the root. If you’re ready to stop living in embarrassment about your sexual function, become an advocate for yourself and your own health and talk to your doctor.
“Although having sex at 70 is not the same as having sex at 20, erectile dysfunction is not a normal part of aging,” according to Michael Feloney, MD, urologic surgeon and expert on sexual dysfunction issues at the Nebraska Medical Center in Omaha. “You should still be able to have a satisfying sex life as you age." If you are experiencing erectile dysfunction, these 10 dos and don'ts may help.
Supplements are popular and often cheaper than prescription drugs for ED. However, supplements have not been tested to see how well they work or if they are a safe treatment for ED. Patients should know that many over-the-counter drugs have been found on drug testing to have ‘bootlegged' PDE 5 Inhibitors as their main ingredient. The amounts of Viagra, Cialis, Levitra or Stendra that may be in these supplements is not under quality control and may differ from pill to pill. The FDA has issued consumer warnings and alerts.
Clinical studies have suggested that these devices are effective and acceptable to a large number of patients with ED of varying causes, including psychogenic erectile failure. These devices are safe and can restore a man’s ability to achieve penetrative intercourse, with one study suggesting nearly 95% success with adequate instruction and support.30 However, satisfaction with this treatment modality typically wanes with time, as patients report dissatisfaction with how cumbersome or unnatural the devices are to use, hinging or buckling of the erection with thrusting, and dissatisfaction with the fact that the erection is ischemic and therefore cold, which can be off-putting to the partner.
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Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).
Falling in love decreases men's testosterone levels while increasing women's testosterone levels. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes.[53] However, it is suggested that after the "honeymoon phase" ends—about four years into a relationship—this change in testosterone levels is no longer apparent.[53] Men who produce less testosterone are more likely to be in a relationship[54] or married,[55] and men who produce more testosterone are more likely to divorce;[55] however, causality cannot be determined in this correlation. Marriage or commitment could cause a decrease in testosterone levels.[56] Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts.[57] Married men who engage in bond-maintenance activities such as spending the day with their spouse/and or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities are more relevant to changes in testosterone levels.[58] 

There is a dirty little secret about testosterone cream that almost no one knows, and I’m going to share it here. Please don’t abuse it. If you take a vanishingly small dose of testosterone cream and apply it to your labia and the vulva (or your partner’s), you will witness a form of vasodilation rarely seen no matter how good you are in bed. It has a profound local effect and will produce a night you won’t forget for years.


Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
Both ED and low testosterone (hypogonadism) increase with age. The incidence of the latter is 40% in men aged 45 years and older. [15] Testosterone is known to be important in mood, cognition, vitality, bone health, and muscle and fat composition. It also plays a key role in sexual dysfunction (eg, low libido, poor erection quality, ejaculatory or orgasmic dysfunction, reduced spontaneous erections, or reduced sexual activity). [16]
In many cases, diagnosing erectile dysfunction requires little more than a physical exam and a review of your symptoms. If your doctor suspects that an underlying health problem may be at play, however, he may request additional testing. Once you’ve determined the cause for your ED, you and your doctor can decide on a form of treatment – here are some of the options:
Sexual dysfunction is highly prevalent in men and women. In the MMAS, 52% of the respondents reported some degree of erectile difficulty. Complete ED, defined as (1) the total inability to obtain or maintain an erection during sexual stimulation and (2) the absence of nocturnal erections, occurred in 10% of the respondents. Mild and moderate ED occurred in 17% and 25% of responders, respectively. [15]

Longitudinal studies in male aging studies have shown that serum testosterone levels decline with age (Harman et al 2001; Feldman et al 2002). Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year. The reduction in free and bioavailable testosterone levels is larger because aging is also associated with increases in SHBG levels (Feldman et al 2002). Cross-sectional data supports these trends but has usually shown smaller reductions in testosterone levels with aging (Feldman et al 2002). This is likely to reflect strict entry criteria to cross-sectional studies so that young healthy men are compared to older healthy men. During the course of longitudinal studies some men may develop pathologies which accentuate decreases in testosterone levels.
Erectile dysfunction (ED) affects 50% of men older than 40 years, [4] exerting substantial effects on quality of life. [5] This common problem is complex and involves multiple pathways. Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems. Any abnormality in these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm.
It appears that testosterone has NOS-independent pathways as well. In one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme. [24] The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity.
In a randomized double-blind, parallel, placebo-controlled trial, sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with ED and low testosterone levels. [19] The objective of the study was to determine whether the addition of testosterone to sildenafil therapy improves erectile response in men with ED and low testosterone levels.

All studies demonstrate a strong association with age, even when data are adjusted for the confounding effects of other risk factors. The independent association with aging suggests that vascular changes in the arteries and sinusoids of the corpora cavernosa, similar to those found elsewhere in the body, are contributing factors. Other risk factors associated with aging include depression, sleep apnea, and low HDL levels.

Associated morbidity may include various other male sexual dysfunctions, such as premature (early) ejaculation and male hypoactive sexual desire disorder. The NHSLS found that 28.5% of men aged 18-59 years reported premature ejaculation, and 15.8% lacked sexual interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% had a lack of pleasure in sex. [51]
Some of the effects of testosterone treatment are well recognised and it seems clear that testosterone treatment for aging hypogonadal men can be expected to increase lean body mass, decrease visceral fat mass, increase bone mineral density and decrease total cholesterol. Beneficial effects have been seen in many trials on other parameters such as glycemic control in diabetes, erectile dysfunction, cardiovascular risk factors, angina, mood and cognition. These potentially important effects require confirmation in larger clinical trials. Indeed, it is apparent that longer duration randomized controlled trials of testosterone treatment in large numbers of men are needed to confirm the effects of testosterone on many aspects of aging male health including cardiovascular health, psychiatric health, prostate cancer and functional capacity. In the absence of such studies, it is necessary to balance risk and benefit on the best available data. At the present time the data supports the treatment of hypogonadal men with testosterone to normalize testosterone levels and improve symptoms. Most men with hypogonadism do not have a contraindication to treatment, but it is important to monitor for adverse consequences including prostate complications and polycythemia.

Erectile dysfunction (ED) is the inability to get an erection or to keep one that's firm enough or that lasts long enough for a man to have a satisfying sexual experience. Occasional bouts of ED aren't unusual. In fact, as many as one in five men deal with erectile dysfunction to some degree. Symptoms, of course, are rather obvious. And while age can be a risk factor, so can medication use, health conditions, lifestyle factors (like smoking), and other concerns. Treatment is available and may involve prescriptions, habit changes, or other options.
Patients receiving penile prostheses should be instructed in the operation of the prosthesis before surgery and again in the postoperative period. The prosthesis usually is not activated until approximately 6 weeks after surgery, so as to allow the edema and pain to subside. The prosthesis is checked in the office before the patient begins to use it.
He said it's also important to point out there may be different thresholds for different people. "One man might get low libido at 325 milligrams per deciliter, while another might not get low libido until 450," he said. As for doctors who say that every man of a certain age will benefit from TRT, Dr. Swerdloff said, "It should not be treatment based on age. It should be treatment based on the best available laboratory and clinical data. Those patients who don't meet the criteria for treatment should not be treated unless there is some logical reason why they are outliers from the usual type of pattern."
When you become aroused, your brain sends chemical messages to the blood vessels in the penis, causing them to dilate or open, allowing blood to flow into the penis. As the pressure builds, the blood becomes trapped in the corpora cavernosa, keeping the penis erect. If blood flow to the penis is insufficient or if it fails to stay inside the penis, it can lead to erectile dysfunction.
Both testosterone and 5α-DHT are metabolized mainly in the liver.[1][147] Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively.[1] An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order.[1][147][148] Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone.[1][147] The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile.[1][147][148] Only a small fraction (2%) of testosterone is excreted unchanged in the urine.[147]

A team led by Dr. Joel Finkelstein at Massachusetts General Hospital investigated testosterone and estradiol levels in 400 healthy men, 20 to 50 years of age. To control hormone levels, the researchers first gave the participants injections of a drug that suppressed their normal testosterone and estradiol production. The men were randomly assigned to 5 groups that received different amounts (from 0 to 10 grams) of a topical 1% testosterone gel daily for 16 weeks. Half of the participants were also given a drug to block testosterone from being converted to estradiol.
There are positive correlations between positive orgasm experience in women and testosterone levels where relaxation was a key perception of the experience. There is no correlation between testosterone and men's perceptions of their orgasm experience, and also no correlation between higher testosterone levels and greater sexual assertiveness in either sex.[34]
Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.
Remember that each person is unique, and each body responds differently to treatment. TT may help erectile function, low sex drive, bone marrow density, anemia, lean body mass, and/or symptoms of depression. However, there is no strong evidence that TT will help memory recall, measures of diabetes, energy, tiredness, lipid profiles, or quality of life.
Erectile dysfunction can be embarrassing and difficult to talk about for some men. Many men may feel like they need to hide their diagnosis from their partner. "Failure to communicate openly about erectile dysfunction can result in both partners drawing away from the relationship," warns Feloney. Remember that your partner is also affected by your problem; being open and honest is the best way to decrease fear and anxiety. Discuss options for achieving sexual satisfaction together, and be positive — most erectile dysfunction problems can be treated.
Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).

Testosterone is only one of many factors that influence aggression and the effects of previous experience and environmental stimuli have been found to correlate more strongly. A few studies indicate that the testosterone derivative estradiol (one form of estrogen) might play an important role in male aggression.[66][67][68][69] Studies have also found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus.[70]
However, testosterone is only one of many factors that aid in adequate erections. Research is inconclusive regarding the role of testosterone replacement in the treatment of erectile dysfunction. In a review of studies that looked at the benefit of testosterone in men with erection difficulties, nearly half showed no improvement with testosterone treatment. Many times, other health problems play a role in erectile difficulties. These can include:
Testosterone is a sex hormone that plays important roles in the body. In men, it’s thought to regulate sex drive (libido), bone mass, fat distribution, muscle mass and strength, and the production of red blood cells and sperm. A small amount of circulating testosterone is converted to estradiol, a form of estrogen. As men age, they often make less testosterone, and so they produce less estradiol as well. Thus, changes often attributed to testosterone deficiency might be partly or entirely due to the accompanying decline in estradiol.
When many people think of someone with a high level of testosterone, they may picture a man loaded with strength, sexual prowess, and machismo. But while high-T has been correlated with all those things, it’s also been correlated with aggression, sexual misconduct, and violence. One of testosterone’s most common uses—as a performance-enhancing steroid—illustrates both sides of the hormone. Injecting steroids can be a quick way for athletes to dramatically improve performance, but the side effects can also be extreme, and can include excessive body hair growth, sexual dysfunction, and the hard-to-corral anger known as “roid rage.”
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."
"One of the reasons erectile dysfunction increases with age is that the diseases that lead to it also increase with age," notes Dr. Feloney. Evaluating the causes of erectile dysfunction starts with your doctor taking a good health history and giving you a physical exam. Common medical issues that can lead to erectile dysfunction include diabetes, high blood pressure, hardening of the arteries, low testosterone, and neurological disease. Talk to your doctor about better managing these health conditions.
Testosterone replacement therapy is currently only FDA approved for men who have been diagnosed with hypogonadism, but it’s also prescribed off-label for older men who take it in hopes that it will improve their libido. The use of testosterone therapy is increasingly common in the United States, with more than 2 million men receiving the therapy. Not every man benefits from taking testosterone supplements. Testosterone is available in different forms, including topicals such as gels, creams, and patches; injections; and pellets that are surgically placed directly beneath the skin. (7)
Studies show that high cholesterol and obesity are linked to erectile dysfunction, and both can be improved through diet. "A heart-healthy diet that prevents cardiovascular disease and maintains a healthy weight is also good for erectile functioning," says Feloney. An ideal diet plan involves eating foods low in saturated fat and cholesterol and having frequent servings of fruits, vegetables, and plenty of whole grains.
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