NO is produced by the enzyme NO synthase (NOS).  NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
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."
Erectile dysfunction - (ED) or impotence is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual activity. A penile erection is the hydraulic effect of blood entering and being retained in sponge-like bodies within the penis. The process is most often initiated as a result of sexual arousal, when signals are transmitted from the brain to nerves in the penis.
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, 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, where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.
The laboratory results should be discussed with the patient and, if possible, with his sexual partner. This educational process allows a review of the basic aspects of the anatomy and physiology of the sexual response and an explanation of the possible etiology and associated risk factors (eg, smoking and the use of various medications). Treatment options and their benefits and risks should be discussed. This type of dialogue allows the patient and physician to cooperate in developing an optimal management strategy.
There is a negative correlation of testosterone levels with plasminogen activator inhibitor-1 (PAI-1) (Glueck et al 1993; Phillips 1993), which is a major prothrombotic factor and known to be associated with progression of atherosclerosis, as well as other prothrombotic factors fibrinogen, α2-antiplasmin and factor VII (Bonithon-Kopp et al 1988; Glueck et al 1993; Phillips 1993; De Pergola et al 1997). There is a positive correlation with tissue plasminogen activator (tPA) which is one of the major fibrinolytic agents (Glueck et al 1993). Interventional trials have shown a neutral effect of physiological testosterone replacement on the major clotting factors (Smith et al 2005) but supraphysiological androgen administration can produce a temporary mild pro-coagulant effect (Anderson et al 1995).
Having learned a great deal more about erectile dysfunction including its risk factors and causes, you should be equipped to assess your own erectile function. If you have experienced erectile issues or you have some of the risk factors mentioned above, it may be worth making a trip to your doctor’s office. If you choose to seek help, give your doctor as much information as you can about your symptoms including their frequency and severity as well as the onset. With your doctor’s help, you can determine the best course of treatment to restore sexual function.
The other interesting thing about the study: men’s testosterone levels were lowest in March (at the end of winter) and highest in August (at the end of summer). Sunlight affects your vitamin D production, so you have seasonal dips and peaks. Get a blood test to check your levels, and if you’re low, take a high-quality vitamin D3 supplement. If you’re going to take D3, take vitamin K2 and vitamin A with it. The three work in sync, so you want them all to be balanced. Here are my dosage recommendations.
Impotence, also known as erectile dysfunction or ED, is a condition in which a man is unable to get or hold an erection long enough to have a satisfactory sex life. Impotence is a common problem, affecting up to half of Australian men between the ages of 40 and 70 years. The risk of developing erectile dysfunction increases as you get older.In the past, doctors considered impotence to be a mainly psychological problem, caused by performance anxiety or stress. Now, doctors know that many cases of impotence have a physical cause, which usually can be treated. Often, a combination of physical and psychological factors contributes to erectile dysfunction.Physical causes of impotencePhysical causes of impotence can include:problems with blood to flow into and out of the penis;damage to the nerves that send signals from the body’s central nervous system to the penis; and, more rarely,a deficiency in testosterone or other hormones.Some medicines can contribute to impotence, as can some types of surgery and radiotherapy treatments.Blocked blood vessels to the penisA very common cause of impotence is when blood flow into the penis is reduced. This can be due to atherosclerosis, also known as hardening of the arteries. In atherosclerosis, the arteries are clogged and narrowed, resulting in reduced blood flow.Risk factors for atherosclerosis include:high cholesterol;high blood pressure;obesity;sleep apnoea;diabetes; andsmoking.If your erection problems are caused by atherosclerosis, there is a chance that the arteries in other parts of your body (e.g. the coronary arteries that supply your heart) are also affected by atherosclerosis. In fact, erection problems may be the first sign that you are at risk of coronary heart disease.Because the arteries to the penis are narrower than those to the heart, you may develop symptoms of erectile dysfunction before you experience any symptoms of heart disease, such as angina. So seeing your doctor about erection problems may be important for your overall physical health.Impotence can also be caused by a blood clot that prevents enough blood from flowing into the penis to cause an erection.Venous leakageIn some men, blood can flow in to the penis easily, but the problem is that it leaks out again, so an erection cannot be sustained. This is called venous leakage. Doctors aren’t certain of the cause of venous leakage, but they can perform surgery to help repair it.Medicines that can cause impotenceMany medicines can cause erection problems as a side effect, including:diuretics (sometimes known as ‘water tablets’ - often used for high blood pressure);high blood pressure medications;cholesterol-lowering medicines (including statins);some types of antipsychotics;antidepressants;cancer treatments;some medicines used to treat heartburn and stomach ulcers;antihistamines;some pain medicines; andcertain epilepsy medications.If you experience impotence after starting a new medication, tell your doctor, who may be able to prescribe a different medicine for you. Don’t stop taking a medicine without first consulting your doctor. You should also tell your doctor about any over-the-counter medicines or complementary remedies you may be taking.The following table contains a list of specific medicines that may cause or contribute to erectile dysfunction. This list may not cover all types of medicines that can cause erectile dysfunction, so always ask your doctor if you are in doubt. Also, for some of these medicines ED is a very rare side effect. Most men taking these medicines do not experience erectile dysfunction.Medicines that may cause erectile dysfunctionType of medicineExamplesACE inhibitorscaptopril (Capoten), enalapril (Renitec), perindopril (Perindo), ramipril (Tritace), and othersAntidepressantsamitriptyline (Endep), clomipramine (Anafranil), desvenlafaxine (Pristiq), fluoxetine (Prozac), paroxetine (Aropax), sertraline (Zoloft), venlafaxine (Altven, Efexor), and othersAnti-epilepticsclonazepam (Rivotril), pregabalin (Lyrica)Antifungalsitraconazole (Sporanox)Anti-ulcer drugscimetidine (Magicul), nizatidine (Tazac), ranitidine (Zantac), and othersBeta-blockerspropranolol (Inderal), metoprolol (Betaloc, Lopresor), and othersOther blood pressure-lowering medicinesclonidine (Catapres), lercanidipine/enalapril (Zan-Extra), losartan (Cozaar), perindopril/amlodipine (Coveram), olmesartan/amlodipine (Sevikar), telmisartan/amlodipine (Twynsta), valsartan/hydrochlorothiazide (Co-Diovan)Calcium-channel blockersdiltiazem (Cardizem), felodipine (Plendil), nifedipine (Adalat)Cholesterol-lowering drugsatorvastatin (Lipitor), ezetimibe/simvastatin (Vytorin), fluvastatin (Lescol, Vastin), gemfibrozil (Ausgem), pravastatin (Pravachol), simvastatin (APO-simvastatin, Lipex, Zocor), and othersDiuretics ('water tablets')bumetanide (Burinex), chlorthalidone (Hygroton), spironolactone (Aldactone), and othersSchizophrenia drugsamisulpride (Solian, Sulprix), haloperidol (Haldol, Serenace), olanzapine (Lanzek, Ozin, Zypine, Zyprexa), paliperidone (Invega), risperidone (Rispa, Risperdal), ziprasidone (Zeldox)Combination cholesterol-lowering and anti-hypertensiveamlodipine/atorvastatin (Caduet, Cadatin)Pain medicinesfentanyl (Denpax, Durogesic), hydromorphone (Jurnista), morphine (Momex SR, MS Contin), oxycodone (OxyContin, OxyNorm, Targin), tramadolMiscellaneousoestrogens, antiandrogens, anticancer drugs and some chemotherapy treatments, baclofen (Clofen, Lioresal); cyproterone (Androcur, Cyprohexal, Cyprostat), degarelix (Firmagon), etoricoxib (Arcoxia), finasteride (Proscar and Propecia), flutamide (Flutamin), rotigotine (Neupro), triptorelin (Diphereline)*The names in brackets are just some examples of the trade names each specific medicine is marketed under in Australia. The medicine may also be known by other trade names.Diabetes and erectile dysfunctionMen who have diabetes have a higher risk of developing impotence than other men. Diabetes contributes to impotence because it can damage blood vessels and cause a type of nerve damage known as peripheral neuropathy.Hormones and impotenceLow levels of the male hormone, testosterone, are more commonly linked to a lowered sex drive, rather than impotence itself. Only a small percentage of cases of impotence are caused by hormone deficiency.Low testosterone levels may be the result of a condition called hypogonadism, in which the testicles don’t produce enough testosterone. More rarely, low testosterone can be caused by the pituitary (a small gland at the base of the brain) not secreting sufficient hormones to stimulate the testes to produce testosterone. The pituitary is also sometimes affected by small benign (non-cancerous) tumours that secrete prolactin, another hormone that can cause impotence.Mildly decreased levels of testosterone are often not due to specific testicular or pituitary problems, but rather stress or depression. In this situation, testosterone replacement is rarely of any benefit.Other hormone problems, including thyroid disease, can also cause impotence.Prostate cancer and erectile dysfunctionThe advanced stages of prostate cancer can affect the nerves and arteries that are vital for an erection.Radiation treatment for prostate cancer can harm the erectile tissues of the penis, and prostate cancer surgery can cause nerve or artery damage to the penis.Treatment for advanced prostate cancer often includes medicines that counteract testosterone, and commonly cause erectile dysfunction as well as loss of sexual interest.Peyronie’s diseasePeyronie’s disease is an uncommon condition that affects a man’s sex life because his penis curves abnormally and causes pain when he has an erection. He might also be unable to have a hard erection. The curvature of the penis is caused by a scar, called a plaque, that forms in the penis.Other physical causes of impotenceSeveral other factors and conditions can contribute to erectile dysfunction, including the following.Depression. Many men find that when they’re suffering from depression, they lose interest in sex and can’t get or keep an erection. Asking your doctor for treatments for depression may help alleviate your erection problems as well.Smoking contributes to vascular disease (disease of the blood vessels), so it can contribute to erectile dysfunction by affecting blood flow to the penis. Giving up smoking often has a beneficial effect on erectile function.Excessive alcohol use. Alcoholism can cause permanent nerve damage, resulting in impotence. This nerve damage is called peripheral neuropathy. Long-term alcohol use can impair the liver’s ability to function, resulting in a hormone imbalance in which a man has too much of the female sex hormone, oestrogen. On a day-to-day level, alcohol dulls the central nervous system, adversely affecting sexual response.Illicit drug use. Illicit drugs such as marijuana, cocaine, heroin, barbiturates, and amphetamines act on the central nervous system, impairing the body’s ability to respond sexually.Certain exercises. Nerve and artery damage can be caused by prolonged cycling, rodeo riding, or use of a rowing machine, resulting in the inability to get an erection. Often, minimising the use of hard bicycle seats and exercise machine seats, as well as correct positioning of the seat, will help restore sexual function.Surgery to organs near the nerve pathways of the penis, such as the bladder, rectum and prostate, can cause nerve or artery damage to the penis, resulting in the inability to have an erection.Injuries. Impotence can be caused by spinal cord injury; injury to your sex organs; or a pelvic fracture, which can cause damage to the nerves of the penis, or damage the blood vessels, resulting in reduced blood flow to the penis.Conditions affecting the nervous system. Multiple sclerosis (MS) and other degenerative diseases of the nervous system, such as Parkinson’s disease, can damage the nerves involved in erections.Psychological causes of impotenceMost cases of impotence have physical causes, but, in some men, psychological factors are the main contributors to impotence.Impotence that’s triggered by psychological factors is more common in men who are sexually inexperienced. Psychological erectile dysfunction may only occur when you’re with just one particular person. You’re also more likely to have morning erections, and be able to have an erection when you masturbate, than men whose impotence has a physical cause.Here are some psychological factors that can have an impact on your erections.Stress and anxietyWhen you’re stressed and focusing on other issues apart from sex, you might find that you don’t want to have sex as often and there might be a drop in your ability to perform when you do try. You might find that tackling the source of your stress can have benefits in the bedroom as well.Fear of failureAnxiety about your sexual prowess (commonly called performance anxiety) can, in itself, contribute to failure. By putting pressure on yourself, you become too anxious to get an adequate erection.Most men experience isolated episodes of erectile failure. Even when the transient physical cause has passed, anxiety that it may recur is sufficient to prevent erection. Anxiety, whether about something specifically sexual or part of a wider anxiety syndrome, is never helpful to good sexual function.Problems with your relationship and impotenceImpotence may be a manifestation of a poor relationship, or a problematic time in a relationship. Sexual boredom, tension or anger among partners, and lack of intimacy and communication are all possible triggers of erectile dysfunction. In these cases, seeing a counsellor may help.It’s worth remembering that impotence is a complex medical condition, which may have more than one cause. For example, if impotence is the result of a side effect of medicine or an underlying disease, the anxiety caused by lack of performance may perpetuate the erectile dysfunction even after the physical cause has been dealt with.Almost any chronic (ongoing) physical or mental health disorder, including those with no direct effect on penile nerves or blood supply, can have a powerful effect on sexuality, sexual self-image and erectile function.If you’re worried about your sexual response or the quality of your erections, don’t be afraid to talk to your doctor, who has access to treatments that can help. Last Reviewed: 16 December 2016
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.
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 nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. 
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 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", 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.
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. 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. 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. In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.
When I first started TRT, my physician prescribed a cream that you rub into your skin. The cream version of TRT is not too convenient, because if someone touches you while you have the cream on, the testosterone can rub off on him/her. This can be really bad around kids or pregnant women. If you’re sleeping next to someone, the cream can get on the sheets and transfer over that way, too. The cream can be annoying, but it works. There’s also a gel version called AndroGel; I skipped it because it doesn’t absorb as well as the cream does.