Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology). These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.
In males, the majority of testosterone is secreted from the testes, hence the term “testosterone”. The hormone is also produced in small amounts by the adrenal gland. The production of this hormone is controlled by the hypothalamus and pituitary gland in the brain. The pituitary gland receives instructions from the hypothalamus on how much testosterone needs producing and passes this information onto the testicles via chemicals and hormones circulating in the bloodstream.
In order to discuss the biochemical diagnosis of hypogonadism it is necessary to outline the usual carriage of testosterone in the blood. Total serum testosterone consists of free testosterone (2%–3%), testosterone bound to sex hormone binding globulin (SHBG) (45%) and testosterone bound to other proteins (mainly albumin −50%) (Dunn et al 1981). Testosterone binds only loosely to albumin and so this testosterone as well as free testosterone is available to tissues and is termed bioavailable testosterone. Testosterone bound to SHBG is tightly bound and is biologically inactive. Bioavailable and free testosterone are known to correlate better than total testosterone with clinical sequelae of androgenization such as bone mineral density and muscle strength (Khosla et al 1998; Roy et al 2002). There is diurnal variation in serum testosterone levels with peak levels seen in the morning following sleep, which can be maintained into the seventh decade (Diver et al 2003). Samples should always be taken in the morning before 11 am to allow for standardization.
Modern drug therapy for ED made a significant advance in 1983, when British physiologist Giles Brindley dropped his trousers and demonstrated to a shocked Urodynamics Society audience his papaverine-induced erection.[35] The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, and orally effective drug therapies.[36][better source needed][37][better source needed]
The second theory is similar and is known as "evolutionary neuroandrogenic (ENA) theory of male aggression".[78][79] Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible.[78] The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low digit ratio as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game.[80] Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.[81][82][83][84][85]

Hacking your testosterone influences everything from body composition to energy levels to mood. It’s easy to eat more butter; it’s hard to visit a doctor and get tested, but that’s what I recommend: know your levels. If you’re 25, you’ll know what your target is when you’re 35. By the time you’ve noticed symptoms of low testosterone, it’s too late to get your “normal” measurements!


Epidemiological data has associated low testosterone levels with atherogenic lipid parameters, including lower HDL cholesterol (Lichtenstein et al 1987; Haffner et al 1993; Van Pottelbergh et al 2003) and higher total cholesterol (Haffner et al 1993; Van Pottelbergh et al 2003), LDL cholesterol (Haffner et al 1993) and triglyceride levels (Lichtenstein et al 1987; Haffner et al 1993). Furthermore, these relationships are independent of other factors such as age, obesity and glucose levels (Haffner et al 1993; Van Pottelbergh et al 2003). Interventional trails of testosterone replacement have shown that treatment causes a decrease in total cholesterol. A recent meta-analysis of 17 randomized controlled trials confirmed this and found that the magnitude of changes was larger in trials of patients with lower baseline testosterone levels (Isidori et al 2005). The same meta-analysis found no significant overall change in LDL or HDL cholesterol levels but in trials with baseline testosterone levels greater than 10 nmol/l, there was a small reduction in HDL cholesterol with testosterone treatment.
Men with medical conditions that may cause a sustained erection, such as sickle cell anemia, leukemia, or multiple myeloma, or a man who has an abnormally-shaped penis, may not benefit from these medications. Also, men with liver diseases or a disease of the retina, such as macular degeneration or retinitis pigmentosa, may not be able to take these medications, or may need to take the lowest dosage.
The aim of treatment for hypogonadism is to normalize serum testosterone levels and abolish symptoms or pathological states that are due to low testosterone levels. The exact target testosterone level is a matter of debate, but current recommendations advocate levels in the mid-lower normal adult range (Nieschlag et al 2005). Truly physiological testosterone replacement would require replication of the diurnal rhythm of serum testosterone levels, but there is no current evidence that this is beneficial (Nieschlag et al 2005).
The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group[183] was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",[184] and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and well-being.[185]
Before assessing the evidence of testosterone’s action in the aging male it is important to note certain methodological considerations which are common to the interpretation of any clinical trial of testosterone replacement. Many interventional trials of the effects of testosterone on human health and disease have been conducted. There is considerable heterogenicity in terms of study design and these differences have a potential to significantly affect the results seen in various studies. Gonadal status at baseline and the testosterone level produced by testosterone treatment in the study are of particular importance because the effects of altering testosterone from subphysiological to physiological levels may be different from those of altering physiological levels to supraphysiological. Another important factor is the length of treatment. Randomised controlled trials of testosterone have ranged from one to thirty-six months in duration (Isidori et al 2005) although some uncontrolled studies have lasted up to 42 months. Many effects of testosterone are thought to fully develop in the first few months of treatment but effects on bone, for example, have been shown to continue over two years or more (Snyder et al 2000; Wang, Cunningham et al 2004).
In males, testosterone is required for the development of male sex organs such as increased penis and testes size. The hormone also promotes the development of sexual male characteristics during puberty such as voice deepening and the growth of armpit, chest and pubic hair. Testosterone plays an important role in maintaining sex drive, sperm production, muscle strength and bone mass. A healthy level of testosterone is also protective against bone disorders such as osteoporosis.
These "disease-awareness" campaigns—ostensibly a public service intended to educate those potentially at risk about a condition they may not even have heard of but "could" have—are subtle, even insidious. They may not mention a specific product, but a bit of sleuthing reveals that their sponsors are usually pharmaceutical companies that "just happen" to manufacture products used to treat the real (or at least alleged) condition.
Erections occur in response to tactile, olfactory, and visual stimuli. The ability to achieve and maintain a full erection depends not only on the penile portion of the process but also on the status of the peripheral nerves, the integrity of the vascular supply, and biochemical events within the corpora. The autonomic nervous system is involved in erection, orgasm, and tumescence. The parasympathetic nervous system is primarily involved in sustaining and maintaining an erection, which is derived from S2-S4 nerve roots.
Low-intensity extracorporeal shock wave therapy has been proposed as a new non-invasive treatment for erectile dysfunction caused by problems with blood vessels. Shock wave therapy machines are now available in some medical practices in Australia. Although there is some evidence that it may help a proportion of men with erectile dysfunction, more research is needed before clear recommendations on its use can be made.
The sexual hormone can encourage fair behavior. For the study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. The rules allowed both fair and unfair offers. The negotiating partner could subsequently accept or decline the offer. The fairer the offer, the less probable a refusal by the negotiating partner. If no agreement was reached, neither party earned anything. Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. Two later studies have empirically confirmed these results.[71][72][73] However men with high testosterone were significantly 27% less generous in an ultimatum game.[74] The Annual NY Academy of Sciences has also found anabolic steroid use which increase testosterone to be higher in teenagers, and this was associated with increased violence.[75] Studies have also found administered testosterone to increase verbal aggression and anger in some participants.[76]
"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)
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.
A number of epidemiological studies have found that bone mineral density in the aging male population is positively associated with endogenous androgen levels (Murphy et al 1993; Ongphiphadhanakul et al 1995; Rucker et al 2004). Testosterone levels in young men have been shown to correlate with bone size, indicating a role in determination of peak bone mass and protection from future osteoporosis (Lorentzon et al 2005). Male hypogonadism has been shown to be a risk factor for hip fracture (Jackson et al 1992) and a recent study showed a high prevalence of hypogonadism in a group of male patients with average age 75 years presenting with minimal trauma fractures compared to stroke victims who acted as controls (Leifke et al 2005). Estrogen is a well known determinant of bone density in women and some investigators have found serum estrogen to be a strong determinant of male bone density (Khosla et al 1998; Khosla et al 2001). Serum estrogen was also found to correlate better than testosterone with peak bone mass (Khosla et al 2001) but this is in contradiction of a more recent study showing a negative correlation of estrogen with peak bone size (Lorentzon et al 2005). Men with aromatase deficiency (Carani et al 1997) or defunctioning estrogen receptor mutations (Smith et al 1994) have been found to have abnormally low bone density despite normal or high testosterone levels which further emphasizes the important influence of estrogen on male bone density.
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.
Cardiovascular disease, and its underlying pathological process atherosclerosis, is an important cause of morbidity and mortality in the developed and developing world. Coronary heart disease in particular is the commonest cause of death worldwide (AHA 2002; MacKay and Mensah 2004). As well as increasing with age, this disease is more common in the male versus female population internationally, which has led to interest in the potential role of sex hormones in modulating risk of development of atherosclerosis. Concerns about the potential adverse effects of testosterone treatment on cardiovascular disease have previously contributed to caution in prescribing testosterone to those who have, or who are at risk of, cardiovascular disease. Contrary to fears of the potential adverse effects of testosterone on cardiovascular disease, there are over forty epidemiological studies which have examined the relationship of testosterone levels to the presence or development of coronary heart disease, and none have shown a positive correlation. Many of these studies have found the presence of coronary heart disease to be associated with low testosterone levels (Reviews: Jones, Jones et al 2003; Jones et al 2005).
TT may help you but it may have adverse (harmful) results. (See discussion of these side effects below.) The Federal Drug Administration (FDA) has said that testosterone drug labels should state that there is a risk for heart disease and stroke for some men using testosterone products. All men should be checked for heart disease and stroke before, and periodically while on, TT. The AUA however, on careful review of evidence-based peer review literature, has stated that there is no strong evidence that TT either increases or decreases the risk of cardiovascular events.
Of the drugs used for depression, tricyclic antidepressants may be associated with erectile problems and other drugs may be substituted to prevent this complication. Currently available substitutes include bupropion, nefazodone, and trazodone. The selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline, paroxetine, citalopram) can also cause difficulties with ED, but they might also have other significant sexual side effects, including decreased libido and anorgasmia.

When a man becomes sexually excited, muscles in their penis relax. This relaxation allows for increased blood flow through the penile arteries. This blood fills two chambers inside the penis called the corpora cavernosa. As the chambers fill with blood, the penis grows rigid. Erection ends when the muscles contract and the accumulated blood can flow out through the penile veins.
In one study, 9.6% reported ‘occasional’ erectile dysfunction, 8.9% reported erectile dysfunction occurring ‘often’, and 18.6% reported erectile dysfunction occurring ‘all the time’. Of these, only 11.6% had received treatment.In another study, only 14.1% of men reported that they had received treatment, despite experiencing erectile dysfunction for longer than 12 months.
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.
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.
The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.
At the present time, it is suggested that androgen replacement should take the form of natural testosterone. Some of the effects of testosterone are mediated after conversion to estrogen or dihydrotestosterone by the enzymes aromatase and 5a-reductase enzymes respectively. Other effects occur independently of the traditional action of testosterone via the classical androgen receptor- for example, its action as a vasodilator via a cell membrane action as described previously. It is therefore important that the androgen used to treat hypogonadism is amenable to the action of these metabolizing enzymes and can also mediate the non-androgen receptor actions of testosterone. Use of natural testosterone ensures this and reduces the chance of non-testosterone mediated adverse effects. There are now a number of testosterone preparations which can meet these recommendations and the main factor in deciding between them is patient choice.
Cosgrove et al reported a higher rate of sexual dysfunction in veterans with posttraumatic stress disorder (PTSD) than in veterans who did not develop this problem. [42] The domains on the International Index of Erectile Function (IIEF) questionnaire that demonstrated the most change included overall sexual satisfaction and erectile function. [43, 44] Men with PTSD should be evaluated and treated if they have sexual dysfunction.

If testosterone deficiency occurs during fetal development, then male characteristics may not completely develop. If testosterone deficiency occurs during puberty, a boy’s growth may slow and no growth spurt will be seen. The child may have reduced development of pubic hair, growth of the penis and testes, and deepening of the voice. Around the time of puberty, boys with too little testosterone may also have less than normal strength and endurance, and their arms and legs may continue to grow out of proportion with the rest of their body.

Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
What you need to know about delayed ejaculation Delayed ejaculation is a sexual disorder that can be distressing for a man and his partner and may disrupt a relationship. There are many reasons why delayed ejaculation occurs, including tissue damage, age, drugs, and the side effects of medication. They may be physiological or psychological. Find out how to get help. Read now
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.
Attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer's type,[100][101][102][103] a key argument in life extension medicine for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone,[104] where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition. 

When females have a higher baseline level of testosterone, they have higher increases in sexual arousal levels but smaller increases in testosterone, indicating a ceiling effect on testosterone levels in females. Sexual thoughts also change the level of testosterone but not level of cortisol in the female body, and hormonal contraceptives may affect the variation in testosterone response to sexual thoughts.[51]

Unlike women, who experience a rapid drop in hormone levels at menopause, men experience a more gradual decrease of testosterone levels over time. The older the man, the more likely he is to experience below-normal testosterone levels. Men with testosterone levels below 300 ng/dL may experience some degree of low T symptoms. Your doctor can conduct a blood test and recommend treatment if needed. They can discuss the potential benefits and risks of testosterone medication, as well.
Effective treatment for erectile dysfunction is available, and for most men will allow the return to a fulfilling sex life. The side effects of the treatment for erectile dysfunction vary depending on the treatment that is used. Some may interrupt the spontaneity of sexual activity. For example, PDE-5 inhibitors typically need to be taken one hour before sex. Side effects may include headaches, indigestion, vasodilation, diarrhoea and blue tinge to vision. Other treatments such as penile injections may cause pain at the injection site, or an erection that will not go down. Treatment options need to be carefully discussed with your doctor to determine which one is best suited to you.
The effects of testosterone in humans and other vertebrates occur by way of multiple mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors.[105][106] Androgens such as testosterone have also been found to bind to and activate membrane androgen receptors.[107][108][109]
Epidemiological data has associated low testosterone levels with atherogenic lipid parameters, including lower HDL cholesterol (Lichtenstein et al 1987; Haffner et al 1993; Van Pottelbergh et al 2003) and higher total cholesterol (Haffner et al 1993; Van Pottelbergh et al 2003), LDL cholesterol (Haffner et al 1993) and triglyceride levels (Lichtenstein et al 1987; Haffner et al 1993). Furthermore, these relationships are independent of other factors such as age, obesity and glucose levels (Haffner et al 1993; Van Pottelbergh et al 2003). Interventional trails of testosterone replacement have shown that treatment causes a decrease in total cholesterol. A recent meta-analysis of 17 randomized controlled trials confirmed this and found that the magnitude of changes was larger in trials of patients with lower baseline testosterone levels (Isidori et al 2005). The same meta-analysis found no significant overall change in LDL or HDL cholesterol levels but in trials with baseline testosterone levels greater than 10 nmol/l, there was a small reduction in HDL cholesterol with testosterone treatment.
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.
Some self-administered measures may be useful in the primary care setting to screen for and evaluate the degree of ED.12 The most commonly used instrument is the International Index of Erectile Function, a 15-item questionnaire that has been validated in many populations and is considered the gold standard to evaluate patients for ED.13 The Sexual Health Inventory for Men is a short-form, 5-item questionnaire developed to monitor treatment progress.12 It is important to recognize that short-form questionnaire does not evaluate specific areas of the sexual cycle, such as sexual desire, ejaculation, and orgasm; however, it may be useful in discussing ED with patients and evaluating treatment results over time.
The reliable measurement of serum free testosterone requires equilibrium dialysis. This is not appropriate for clinical use as it is very time consuming and therefore expensive. The amount of bioavailable testosterone can be measured as a percentage of the total testosterone after precipitation of the SHBG bound fraction using ammonium sulphate. The bioavailable testosterone is then calculated from the total testosterone level. This method has an excellent correlation with free testosterone (Tremblay and Dube 1974) but is not widely available for clinical use. In most clinical situations the available tests are total testosterone and SHBG which are both easily and reliably measured. Total testosterone is appropriate for the diagnosis of overt male hypogonadism where testosterone levels are very low and also in excluding hypogonadism in patients with normal/high-normal testosterone levels. With increasing age, a greater number of men have total testosterone levels just below the normal range or in the low-normal range. In these patients total testosterone can be an unreliable indicator of hypogonadal status. There are a number of formulae that calculate an estimated bioavailable or free testosterone level using the SHBG and total testosterone levels. Some of these have been shown to correlate well with laboratory measures and there is evidence that they more reliably indicate hypogonadism than total testosterone in cases of borderline biochemical hypogonadism (Vermeulen et al 1971; Morris et al 2004). It is important that such tests are validated for use in patient populations relevant to the patient under consideration.
There are many effective treatments for impotence. The most popular is a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. These include sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis) and avanafil (STENDRA). These drugs are taken in pill form. They work in most men. But they are less effective in men with neurological causes of impotence.
A vacuum erection device is a plastic tube that slips over the penis, making a seal with the skin of the body. A pump at the other end of the tube makes a low-pressure vacuum around the erectile tissue, which results in an erection. An elastic ring is then slipped onto the base of the penis. This holds the blood in the penis (and keeps it hard) for up to 30 minutes. With proper training, 75 out of 100 men can get a working erection using a vacuum erection device.
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