Hormones, Anabolic Steroids, ARV's and HIV

Posted by Pozziepinoy on 6:07 PM


What are hormones?

A hormone is a chemical messenger released by a cell, a gland, or an organ in one part of the body that affects cells in other parts of the organism.  It is most often used to denote chemicals produced by the endocrine glands.  Hormones play a key role in maintaining homeostasis (a steady state of equilibrium) and regulating many bodily processes -- everything from growth and metabolism to sexual function and reproduction. Over- or underproduction of endocrine hormones can contribute to a wide variety of medical conditions.  Because hormones are involved in so many different bodily processes, diseases such as HIV that affect the whole body can interfere with proper endocrine function, and hormones, in turn, can affect HIV disease progression.  Testosterone and estrogen are the 2 groups of sex hormones that respectively promote the development and maintenance of male, female characteristics of the human body.



What is Testosterone?

Testosterone is a sex hormone, also known as androgen, found in both men and women.  In females it is typically produced at very low levels by the ovaries and adrenal glands and helps regulate muscle and bone development.  In men, it is produced by the testes and adrenal glands at much higher levels and helps maintain sex drive, the production of sperm cells, male hair patterns, and muscle and bone mass.

Testosterone Replacement Therapy (TRT) in people with HIV

In the years before the introduction of combination ARV treatment, AIDS-wasting syndrome was quite common. Scientists eventually learned that more than half of all men with the syndrome also had low levels of testosterone (hypogonadism), and they began experimenting with synthetic testosterone and the chemically related anabolic steroids, as a way to counteract wasting. Early studies showed significant success with TRT in helping people regain muscle mass, and the use of this therapy became highly prevalent.  Thus testosterone supplements are used to treat low testosterone levels which can develop in people with HIV due to HIV infection, some other infections, ARVs and other medications.  It is estimated that as many as 40% of HIV-positive men who are ill because of HIV have low hypogonadism.  Low testosterone can result in decreased appetite, depression, poor metabolism of food, and sexual problems, including the inability to obtain and maintain an erection.

A blood test can show if you have low levels of testosterone and your doctor may prescribe either a short course of oral TRT, testosterone patches, or testosterone gel.
Although testosterone is usually considered to be the male sexual hormone, it also occurs naturally in women. Testosterone patches have been examined as a treatment for wasting caused by HIV in women.  It was found that weight and quality of life improved for some women, and the development of male characteristics was not reported.
TRT Benefits and Risks

Judith Rabkin, PhD, MPH, a professor of clinical psychology at Columbia University’s College of Physicians and Surgeons, has spearheaded several studies of TRT in hypogonadal HIV-positive men.  Her research has focused on fighting the more common symptoms of hypogonadism seen since the advent or ARVs, including depression, fatigue, decreased libido and erectile dysfunction.

In one study, which compared injections of 400 milligrams of testosterone cypionate every other week with a placebo, Rabkin found that men who received testosterone were more than twice as likely as placebo recipients to report improvements in physical energy, mood and sexual function.

In 2006, the Endocrine Society, the leading group representing hormone-specializing endocrinologists in the United States, issued guidelines on testosterone replacement in hypogonadal men. Because of the potential for side effects with TRT, and the fact that plenty of men do not display symptoms of hypogonadism despite low testosterone levels, the group recommended against routine screening of the general male population. They did, however, acknowledge that HIV-positive men are at increased risk for hypogonadism and recommend short-term TRT for those found to be testosterone-deficient, just to bring testosterone levels back within the normal range. Rabkin agrees with these recommendations, saying, “When [testosterone levels] are below the reference range, there’s no question that, medically, [TRT is] indicated.”

Some studies have revealed that non-injectable TRT may offer safer results without the pain of a needle stick. Scott’s research focused on testosterone gel, which is rubbed into the skin daily and can do a better job of keeping testosterone levels steady, as opposed to the “peaks and valleys” frequently seen with injections. “When we give somebody injectable testosterone they get really high levels…and then they crash lower than they should be, and they feel bad. The gel levels that out,” says Scott.

But long-term research on the safety, tolerability and efficacy of TRT in older HIV-positive men is lacking. Indeed, Rabkin acknowledges that most of the research on testosterone in HIV-positive men has involved men in their thirties.

Additionally, as most men pass the age of 50, their risk for developing problems with their prostate gland, including prostate cancer, increases—and TRT can increase this risk and exacerbate prostate problems. According to Rabkin, “Testosterone becomes a little risky for older men, and the age of our patients has increased over time.” The Endocrine Society guidelines recommend that men be carefully screened and monitored for prostate problems before and after being given testosterone therapy.

Prostate troubles aren’t the only concern with testosterone. Other side effects can include worsening of a sleep disorder called sleep apnea, growth of breast tissue, acne, mood volatility, testicular atrophy, reduced sperm count and male-pattern baldness.
Though the guidelines recommend at least short-term use of testosterone in HIV-positive men to augment ARV treatment in reducing muscle wasting, Rabkin found that men’s testosterone levels plummeted within days after stopping treatment to the same levels they were before treatment started. She asserts that most men with hypogonadism cannot sustain normal hormone ranges after initial TRT and will probably require life-long testosterone augmentation.

People with HIV should consult with their physician and weigh all the potential risks and benefits of TRT. If they’re found to have testosterone levels lower than the normal reference range on at least two tests and are experiencing symptoms, therapy may be warranted. For people without symptoms, the data are less clear, and safety concerns may weigh more heavily.

Side-effects from testosterone replacement therapy are rare, but can include the shutting down of natural testosterone production, shrinking of the testicles, hair loss, increased sexual desire, and aggression.  In women, male characteristics, such as the deepening of the voice and facial hair may develop but do so with less frequency than with steroid use/abuse.

 What is HRT? 

Therapy consisting of estrogen or a combination of estrogen and progestin designed to replace the loss of these hormones in menopause. Hormone therapy is used to combat the effects of hormone deficiencies including bone loss, vaginal atrophy, hot flashes, and other menopausal conditions.  Estrogen/testosterone combinations may also be used.
What is Estrogen?

Estrogen is a sex hormone that is also found in both men and women.  In men it is typically produced at very low levels in the testicles to prevent premature programmed cell death (apoptosis), of male sperm cells helps regulate muscle and bone development.  It helps regulates the cardiovascular system in both man and women.  In women it is produced chiefly by the ovaries and responsible for promoting estrus and the development and maintenance of female secondary sex characteristics.

Hormone Replacement Therapy (HRT), in people with HIV.

As HIV-positive women live longer, they are subject to the same age-related hormonal changes as their HIV-negative counterparts. The use of hormone replacement therapy (HRT) in women with or without HIV is currently controversial. Once routinely recommended both for ameliorating acute menopausal symptoms and for preventing problems such as osteoporosis, heart disease, and cognitive decline, long-term HRT has fallen out of favor in the wake of studies showing that estrogen, with or without progesterone, appears to confer more risks than benefits.

Menopause typically ensues between the late thirties and late fifties. During menopause and the preceding period known as peri-menopause, declining estrogen levels can cause symptoms such as hot flashes, night sweats, insomnia, fatigue, depression, irritability, forgetfulness, and vaginal thinning and dryness. The more intense symptoms typically improve over two to three years as hormone fluctuations even out.  A careful differential diagnosis is necessary to avoid confusing symptoms of menopause with those related to HIV itself, Opportunistic Infections (OIs), or ARVs.

For young women who experience premature amenorrhea before the normal age of menopause, oral contraceptives may be used to restore levels of estrogen and progesterone and re-establish normal menstrual cycles.  For older women undergoing menopause, physicians have, in the past, traditionally offered HRT using oral estrogen (e.g., Premarin) or estrogen plus progesterone (e.g., Prempro).

However, in July 2002 the estrogen/progesterone arm of the Women's Health Initiative (WHI) HRT study, which included more than 160,000 post-menopausal women, was discontinued after data showed that combination HRT increased the risk of breast cancer, heart attacks, and strokes (although the absolute risk was small). HRT did lower the risk of hip fractures and colon cancer, but the researchers concluded that the overall risks outweighed the benefits. In March 2004, the estrogen-only arm of the study was also halted after seven-year data revealed that estrogen not only failed to provide the hoped-for cardiovascular benefits, but also appeared to slightly raise the risk of strokes. (Because estrogen without progesterone increases the risk for uterine cancer, this arm included nearly 11,000 women who had undergone hysterectomies.)

As it stands, the risks and benefits of HRT in women with HIV remain unknown. HIV-positive women could conceivably benefit from the bone-preserving effects of estrogen, especially since some studies suggest that HAART or HIV itself are associated with a higher risk of osteoporosis. At the same time, women on HAART may be at higher risk for HRT-related heart attacks or strokes due to dyslipidemia and other side effects associated with antiretroviral therapy, and may be at greater risk for cancer due to immune suppression.  Despite this uncertainty, many physicians believe that HRT remains a viable short-term strategy for relieving disabling menopausal symptoms. "I give the same recommendations to women with HIV as I do to HIV-negative women," says Lori Kamemoto, M.D., of the University of Hawaii in Honolulu. "If you have severe, intractable post-menopausal symptoms, and you've tried waiting it out, perhaps you're one of those who need HRT."   However, most experts now agree that routine, long-term use of HRT solely to prevent heart disease or osteoporosis is inappropriate. Medications such as Alendronate (Fosamax) and Risendronate (Actonel) may help prevent bone loss without the risks of HRT.  For women with low levels of estrogen and/or progesterone, there are other options beside oral hormone supplements. Estrogen and progesterone are also available in creams, patches, and vaginal rings that deliver lower doses and thus may not carry the same risks.  Please note that HRT may interact with the ARVs you are currently on.  Thus women on ARVs who are also considering HRT should inform both Doctors of their respective conditions or, ideally, have the same Medical Doctor treat them for both so that any potential interactions can be avoided or ameliorated.

The US Department of Health and Human Services recommends in its guideline titled Medical care for menopausal and older women with HIV infection that “Clinicians should refer HIV-infected women experiencing severe symptoms of menopause to a clinician experienced in the most current management of menopausal symptoms.  An individualized risk/benefit analysis of the use of HRT should be performed regardless of whether or not the woman is receiving HAART.  Clinicians should discuss with HIV-infected women the benefits of exercise, weight control, improved nutrition, including calcium supplementation, and smoking cessation for the prevention of osteoporosis and coronary heart disease.”

Hormones and Transgender Individuals with HIV

HIV-positive transgender individuals who are using hormone therapy for gender transition face some special concerns. Individuals transitioning from male to female usually take oral estrogen (with or without androgen-blocking drugs), while individuals transitioning from female to male typically use injected testosterone and sometimes aromatase inhibitors to block the conversion of testosterone to estrogen.

Hormone doses used for sex reassignment are higher than those used for contraception or hormone replacement therapy. The risk of adverse short-term side effects and long-term consequences (such as liver problems, cancer, and heart disease) is therefore greater. The effects of large hormone doses on HIV-positive transgender individuals have not been well studied, nor has the interaction between hormones and antiretroviral medications or the impact of hormones on CD4 counts for transgender persons.

Concurrent use of hormone therapy, especially oral estrogens, and certain NNRTIs and PIs may lead to either increased or decreased hormone levels. This has been seen with the ethinyl estradiol and norethindrone in oral contraceptives.  If drug interactions lead to lower blood estrogen levels, this may cause the return of male features such as facial and body hair growth for transgender women.  Levels of anti-HIV medications could potentially also be affected, leading to either subtherapeutic antiretroviral drug levels or intensified side effects. Transgender men usually take large testosterone doses by injection, thus bypassing the drug-metabolizing cytochrome P450 enzyme system in the liver.  Interactions have not been documented between antiretroviral drugs and testosterone, although the possibility cannot be excluded.

Transgender individuals with HIV who are taking hormones should receive care from a physician or medical team that has experience with both HIV treatment and hormone therapy for sex reassignment. While taking hormones, it is important to have levels checked regularly, along with monitoring tests for side effects such as liver toxicity and abnormal blood fat levels.

JoAnne Keatley, MSW, Director of the Center of Excellence for Transgender HIV Prevention, UCSF says “We don't fully understand the impact of hormones by themselves on the transgender body, and we know even less about how hormones interact with HIV meds."

Having said all of this, cross-gender hormone therapy is not contraindicated in HIV-positive people on antiretroviral therapy (ART) at any stage of HIV-disease progression.  Health care providers may still be wary, as there is so little medical literature on interactions between hormone therapy and antiretroviral drugs or the impact of hormones on CD4 counts for transgender persons.  There is some evidence that certain HIV medications do impact hormone levels; for example, TWHC advises extreme care with the protease inhibitor Indinavir (Crixivan) and the non-nucleoside reverse transcriptase inhibitor Efavirenz (Sustiva), as they may increase levels of ethinyl estradiol, a form of the hormone estrogen. TWHC also advises transgender patients on hormone therapy to avoid the protease inhibitors Fosamprenavir (Lexiva) because hormone therapy may decrease blood levels of these drugs by 20%, putting the patient at risk for drug-resistant HIV.   Thus, every HIV+ transgender person using hormones and ARVs must have their health status monitored assiduously, and on an individual basis by a HIV Medical Specialist.

HIV Medications That Increase Estradiol and Ethinyl Estradiol Levels

Protease Inhibitors:  Atazanavir (Reyataz), Fosamprenavir (Lexiva), Indinavir (Crixivan)

Non Nucleoside Reverse Transcriptase Inhibitors:  Efavirenz (Sustiva), Delavirdine (Rescriptor), Etravirine (Intelence), Saquinavir (Invirase)

HIV Medications That Decrease Estradiol and Ethinyl Estradiol Levels
Protease Inhibitors:  Lopinavir/Ritonavir (Kaletra/Aluvia), Darunavir (Prezista), Nelfinavir (Viracept), Ritonavir (Norvir), Tipranivir (Aptivus)

Non Nucleoside Reverse Transcriptase Inhibitors:  Nevirapine (Viramune)

 Other Drugs Commonly Used by HIV Positive Persons That Increase Estradiol and Ethinyl Estradiol Levels
cimetidine (Tagamet), clarithromycin (Biaxin), diltiazem (Cardiazem), erythromycin (E-mycin, Ery-Tab, Eryc), fluconazole (Diflucan), fluoxetine (Prozac, Sarafem), isoniazid (Lanizid, Nydrazid), itraconazole (Sprononox), ketoconazole (Nizoral), paroexetine (Paxil), sertraline (Zoloft), verapamil (Calan, Covera, Isoptin, Veralan)

Other Drugs Commonly Used by HIV Positive Persons That Decrease Estradiol and Ethinyl Estradiol Levels
dexamethasone (Decadron),phenobarbital (Luminal), phenylbutazone (Azolid, Butazolidin),phenytoin (Dilantin), progesterone (Crinone, Prochieve, Prometrium, Provera), rifampin (Rifadin, Rimactane)

It is important to note that the quantities of hormones required for feminization and masculinization have not been thoroughly tested for interactions with other drugs. Drug interactions involving ethinyl estradiol -- a form of estrogen used in birth control pills -- offer some hints, but much higher doses of ethinyl estradiol are prescribed for hormone therapy for transgender persons compared with those taken for birth control. Decreased or increased levels of ethinyl estradiol in the body may lead to unwanted side effects, ranging from inadequate feminization of physical features to nausea and vomiting, headache, and drowsiness.


What are anabolic steroids?

Anabolic steroids are an artificial (synthetic) steroid hormone that resembles the male hormone testosterone in promoting the growth of muscle.  They also enhance masculine characteristics.   Such hormones are used medicinally to treat some forms of weight loss, delayed puberty, certain types of anemia, and other medical problems that cause the body to make very low amounts of testosteroneThey are also used illegally by some athletes, body builders and others to enhance physical performance. 

Because they can help the body to form lean muscle, they are sometimes used to treat wasting and weight loss caused by HIV.  Doctors sometimes prescribe them for people experiencing fat loss from the limbs because of lipodystrophy and lipoatrophy sometimes observed during antiretroviral therapy.  The characteristic morphological changes observed are highly stigmatizing to individuals and may lead to consideration of delaying commencement of therapy, modification of established therapy to alternative regimens or decisions to stop therapy to prevent or attempt to manage the problems.   

Anabolic steroid treatment in people with HIV

Human immunodeficiency virus type 1 (HIV-1) is frequently associated with weakness and muscle wasting, referred to as HIV-1 wasting myopathy (AIDS wasting).  AIDS wasting can lead to organ failure and shortened lifespan.  Doctors sometimes prescribe them for people experiencing wasting syndrome (wasting caused by HIV) as well as fat loss from the limbs because of lipodystrophy and lipoatrophy sometimes observed during antiretroviral therapy.  Anabolic steroids have been studied as a treatment for wasting caused by HIV, and have been shown to be safe and effective, helping the formation of lean muscle mass.  In the United States, nandrolone decanoate and oxandrolone have been used to help increase weight and muscle mass in small studies of people with wasting.  To be most effective, anabolic steroid treatment should be combined with an exercise program of resistance (weight) training both of which need to be done Under Medical Supervision by a HIV Medical Specialist.  Wayne Dodge, M.D., the HIV/AIDS program director at the Group Health Cooperative in Seattle, suggests that clinicians should obtain blood testosterone levels, “if an HIV-infected individual has had significant weight loss, significant fatigue or muscle wasting, and particularly if associated with a significant decrease in libido and erections. If [testosterone] is in the low or low-normal range then a trial of [steroids] could be tried. The individual and the clinician should decide what result would constitute a successful trial: weight gain of 15 pounds, a 30 percent improvement in sense of well-being [or] a successful erection once a week.”  Under Medical Supervision by a HIV Medical Specialist, they can be a safe and effective in treating HIV wasting syndrome and adding lean muscle mass.  An HIV Medical Specialist will need to monitor any HIV+ persons liver function and integrate this knowledge when deciding at which point the PRESCRIBED steroid use should cease.  Note that studies have mostly been restricted to men because of concerns about the side-effects of steroid treatment for women.

What problems can abusing anabolic steroids cause?
Many ARVs, such as Zidovudine, Stavudine, Didanosine (ddI) and other nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitor such as Kaletra (Aluvia), non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as Efavirenz and Nevirapine are processed by the liver.   Anabolic steroids are also processed by the liver and thus have the potential to interact with the metabolism or ARVs.  For HIV+ people Protease inhibitor such as Kaletra (Aluvia), as well as can also raise the level of bad cholesterol (LDL) and lower levels of good cholesterol (HDL).  Anabolic steroids can also do this and thus, the effect can be increased when steroids are abused.  Long-term use which is NOT MEDICALLY SUPERVISED can cause serious side effects for everybody. Some of these effects can be permanent.

In men, anabolic steroids can cause:  The shutting down of natural testosterone production, reduced sperm count, testicular shrinkage, breast enlargement and infertility.
In women, anabolic steroids can cause:  The development of male characteristics such as increase body hair, rougher skin, decreased breast size, an enlarged clitoris, and deepening of the voice.

In both men and women, anabolic steroids can cause: Bone growth to stop before it is complete in a teen and the teen may not reach his or her full adult height, demineralization of the bones in adults, a heart attack or stroke, even in a very young person, high blood pressure, higher levels of bad cholesterol (LDL) and lower levels of good cholesterol (HDL), severe liver problems including liver fibrosis, cirrhosis and cancer.  These can also be the unwanted side effects of taking some ARVs.  Thus, their severity may be increase when steroids use is not medically supervised.  Note, the chance of these problems is higher when steroids are taken as a pill but can also occur when injected.  When injected they more frequently cause, oily skin and acne, male-pattern hair loss, skin infections that can be very severe if the steroids aren’t sterile, irritability, rage (“roid rage”), uncontrolled high energy (mania), or false beliefs (delusions).  People who abuse anabolic steroids can have withdrawal symptoms when they stop taking them.  Symptoms include having extreme mood swings, being extremely tired, having no desire to eat, and craving steroids.

Any drug that is obtained illegally is almost certain to contain adulterants of some sort or, in the case of steroids, a lack of the steroid itself. Counterfeit steroids are common and may contain impurities that cause skin infections or abscesses that can become severe if the drug was tainted with bacteria.  The dose of illegal anabolic steroids may 10 to 100 times higher than the dose a doctor prescribes for medical problems.  People often use more than one of these illegal drugs at the same time.  This is called stacking.  Or they may take the drugs in a cycle from no drug to a high dose over a period of weeks to months. This is called pyramiding.  Consequently the unwanted side effects may increase proportionally.

I hope readers have found this post useful.

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Get tested, stay healthy and, if you’re HIV+, compliant with your ARV regimen,

Malcolm Brown.
International Contributor









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