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Anabolic Therapies for HIV poz men
Aug 11, 2003

I have been doing some research into Anabolic steriod therapy for HIV poz guys. What is your oppion of this type of therapy.

Response from Dr. Moyle

I am generally unenthusiastic about anabolic agents although I am happy to supplement testosterone in individuals who are consistently hypogonadal. Testosterone and its derivative drugs predominantly increase lean body muscle mass and are thus well-suited for managing wasting where no cause for weight loss is found. Controlled trials in both eugonadal and hypogonadal men with HIV infection have shown benefit [1,2] although an intensive exercise program may be equally effective as testosterone for weight gain [3]. Exogenous anabolic steroids interfere with natural anabolic production hence patients may feel diminished energy, a modest loss of appetite, diminished sexual desire or function and may lose some lean body and total weight after withdrawal. These symptoms (and measurement of a low testosterone) may prompt re-institution of therapy; reinforcing a physical and psychological dependency [4]. Eventually, as the disruption of the hypothalamic-pituitary axis resolves, natural anabolic production resumes these symptoms may resolve. The time taken for return to normal values varies but 6 weeks or more may be necessary. Some physicians use b-HCG to stimulate natural anabolic production at the end of a course of anabolics although this approach has not been systematically evaluated [5] and addresses the problem at the level of the pituitary but not the hypothalamus. No data on using gradual de-escalation of doses have been reported but it is unlikely to help reinitiate normal testosterone production. Additionally, as CYP3A4 is responsible for metabolism of a number of endogenous substances including testosterone, cortisol, progesterone, androstanediol, dehydroepiandosterone-3-sulphate (DHEAs) and estradiol, interactions with inhibitors (e.g. PIs especially RTV) or inducers (e.g. EFV and NVP) of this enzyme by influence exposure of these agents. [6]. Switching from a PI based to a NNRTI based regimen may be beneficial of recovery of levels of testosterone although this has not been formally tested. In men with low testosterone levels or hypogonadism, replacement of testosterone to physiologic levels is appropriate and may be accompanied by clinical benefits. Proven benefits include a shift into positive nitrogen balance, increases in lean body mass, and improved exercise performance. [2] Additionally, supplementation may be accompanied by improvements in energy, libido, sexual function and appetite (possible secondary to suppression of leptin) [7].

Chronic anabolic steroids (mis)use may be associated with a range of adverse effects. Gain in muscle mass is often in part at the expense of subcutaneous fat potentially worsening lipoatrophy in the periphery. Clinical lipodystrophy with facial fat pad wasting has been reported in a person self-administering nandrolone deconate and other anabolic agents for body-building [8]. Risk of gynaecomastia may also increase due to conversion of anabolics into oestrogen related substances in the periphery. Besides the well-known increased risk of hepatic [9, 10] and possibly germ line tumors [11] these agents are commonly associated with elevations in liver function. This may add confusion to the early diagnosis of lactic acidosis and complicate the management of hepatitis B or C co-infection. Specifically for this Hepatitis B co-infected individual, use of anabolic steroids represent an additional risk factor for hepatocellular carcinoma. Specifically, raised testosterone levels have been noted as an additional risk factor for HCC in persons with chronic viral hepatitis [12]. The impact of anabolics on progression of hepatitis B has not been reported but both represent risks for hepatic fibrosis. Liver function test disturbances are said to be less common with synthetic steroids than administered testosterone. Metabolic disturbances associated with androgens include falls in HDL cholesterol.[13] As HDL may already be low due to HIV infection and LDL may be elevated due to protease inhibitor use, anabolic agents may further contribute to a increased risk of future ischemic heart disease. Long-term use of anabolic steroids may lead to personality changes [4] and shortly after administration individuals may experience a transient immunosuppression [14], potentially increasing the risk of immune dysfunction related infections. The potential for misuse is well-recognised to such a degree that it is listed as the drug abuse by the American psychiatric association.

In summary, it would be prudent wherever possible to avoid exogenous anabolic steroid administration.

References

Strawford A, Barberi T, Van Loan M, et al. Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss. JAMA 1999;281;1282-1290. Strawford A, Van Loan M, King J, Hellerstein M. Effects of nandrolone deconate on nitrogen balance, lean body mass, metabolic abnormalities and performance in borderline hypogonadal men with HIV-associated weight loss. J Acquir Immune Defic Syndr Hum Retrovirol 1998;20:137-147. Grinspoon S, Corcoran C, Parlman K, et al. Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Ann Intern Med. 2000 Sep 5;133(5):348-55 Kashkin KB; Kleber HD. Hooked on hormones? An anabolic steroid addiction hypothesis JAMA 1989 Dec 8;262(22):3166-70 Gill GV Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin. Postgrad Med J 1998;74:45-6 De Wildt SN, Kearns GL, Leeder JS, van der Anker JN. Cytochrome P450 3A. Ontogeny and drug disposition. Clin Pharmacokinet 1999;37:485-505 Hislop MS; Ratanjee BD; Soule SG; Marais AD Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men. Eur J Endocrinol 1999 Jul;141(1):40-6 O'Mahony C, Price LM, Nelson M. Lipodystrophy despite anabolic steroids. Int J STD AIDS 1998;9(10):619. Henderson JT; Richmond J; Sumerling MD Androgenic-anabolic steroid therapy and hepatocellular carcinoma. Lancet 1973 Apr 28;1(7809):934 Trichopoulos D. Etiology of primary liver cancer and the role of steroidal hormones. Cancer Causes Control 1992;3(1):3-5. Vogelzang NJ, Arnold JJ, Chodak GJ, Schoenberg H. Androgen and germ cell testicular cancers. JAMA 1986;255(7):906. Chen CJ; Yu MW; Liaw YF Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol 1997 Oct;12(9-10):S294-308 Masarei JR, Lynch WJ. Lowering HDL cholesterol by androgens. Lancet 1977;2:827-828. Mendenhall CL, Grossman CJ, Roselle GA, et al. Anabolic steroid effects on immune function: differences between analogues. J Steroid Biochem Mol Biol 1990;37:71-6



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