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Polycythemia, Anabolic Steroids and HIV Wasting

Posted Dec 18 2008 7:28pm
Some HIV positive people need to gain lean body mass and weight but develop polycythemia when using nandrolone or other anabolics, so their doctors refuse to prescribe these important medicines. Polycythemia is an increase in red blood cells and hematocrit that can cause increased blood viscosity, making it more difficult for the heart to pump blood. This can cause heart attackes or strokes, so it is important to know how to manage this problem. Lyckily, only a very small number of people using anabolics have this problem. We still do not know what makes one person more suceptible than other.

I had this problem for 5 months back when I was on Crixivan. For reasons that I do not understand yet, it went away once I stopped Crixivan. I also think using AZT may have a controlling effect on red blood cells.

This first article explains why anabolics increase red blood cells

Anabolic Steroids and Red Blood Cells http://www.mesomorphosis.com/articles/llewellyn/steroids-and-red-blood-cells.htm


Dr Scally has been able to write a very good article to teach doctors how to manage the problem

How to Manage Polycythemia Induced by Anabolic Steroids
By Michael C. Scally M.D.

For better formatting , see
http://health.groups.yahoo.com/group/PozHealth/message/16494

Dr. Michael C. Scally a Harvard and MIT trained physician and researcher in private practice in Houston who has written extensively on hormonal issues and HIV.

During the past few years, his focus have been on managing induced hypogonadism (low testosterone production by the body) after anabolic steroid therapy by restoring HPGA (Hypothalamic Pituitary Gonadal Axis) and managing polycythemia (increased red blood count that increases blood viscosity and cardiovascular disease risks.) This takes on particular importance as hormonal therapies become standard of care in HIV. His development of a new therapeutic approach is detailed in this report, and we are very excited to make it available to our readers.

Anabolic Steroid Use in HIV: Managing Androgen Induced Polycythemia and Hypogonadism

Wasting is one of the most common symptoms of human immunodeficiency virus (HIV). Wasting syndrome is widely considered the involuntary loss of 10% of initial body weight, many times in combination with diarrhea, weakness, and fever (Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR Morb. Mortal Wkly. Rep. 1987; 36 Supp.l 1). This condition may be attributed from malnutrition, diarrhea, altered metabolism, malabsorption, or hypogonadism associated with HIV infection. Since there is an increased mortality rate of HIV patients suffering with substantial body weight loss, aggressive therapies aimed at retaining lean body mass have been pursued.

One particular modality that has shown to be effective in preserving lean body weight is anabolic androgenic steroid (AAS) or androgen therapy. Multiple studies have evaluated the effects of androgens on combating wasting in HIV+ males. These reports have shown significant improvements in lean body mass up to 5.6 kg over short-term usage. While other HIV associated wasting and retroviral therapies may improve total body weight, androgen therapy has demonstrated an increase in fat free weight without a concurrent increase in fat mass. Unfortunately, therapies utilizing protease inhibitors or dietary counseling for wasting syndrome have found larger increases in fat tissue than improvements in muscle mass, thus granting minimal improvements in immune function and metabolism.

Along with the documentation and dissemination of the benefits of androgen therapy in treating wasting syndrome has come an associated acceptability within the medical community in prescribing these medicines. Research articles discussing the use of androgens in HIV+ patients are becoming more prevalent in the medical literature. A drawback of the increased utilization of androgens, however, are those scenarios where patients are administered these medicines for lengthy durations. Extended, uninterrupted use of androgens has been shown to induce polycythemia. Defined as a chronic myeloproliferative disorder characterized by an increase in hemoglobin concentration and red blood cell (RBC) mass (erythrocytosis), polycythemia increases the risk of thrombosis, post polycythemia myeloid metaplasia, and acute leukemia. Androgens, by increasing the endogenous production of erythropoietin, enhance the body’s rate of erythropoiesis and subsequently hemoglobin and RBC mass. With increased viscosity of the blood and platelets, an increased risk of blood clotting, heart attack, and stroke becomes a primary concern with patients afflicted with polycythemia. In terms of androgens, uninterrupted treatment may potentially do greater harm than good when faced with the possibility of problematic polycythemia secondary to androgen therapy.

The following is a report of problematic polycythemia as a result of long-term androgen therapy in an HIV+ male.

Case

A 46-year old HIV+ male presented with complaints of shortness-of breath, fatigue, excessive sweating and facial erythema. Medical history revealed a record of uninterrupted testosterone administration for the two years prior to presentation. The patient was administered testosterone cypionate, 200 mg IM per week, for two years to help sustain lean muscle mass in the prevention of HIV associated wasting syndrome. Laboratory studies revealed polycythemia but were otherwise unremarkable. An attempt at discontinuation of androgen therapy precipitated problematic hypogonadism exhibited by lethargy, diminished libido, decreased energy, sleep disturbance and depression. Testosterone treatment was restarted and the patient referred for consultation.

On presentation vital signs and weight, 75kg, were within normal limits. Original baseline laboratory studies prior to testosterone administration revealed normal CBC and hormone profile, Table 1.

Table 1.

Test
Hgb (gm/dL)
Hct (%)
RBC (M/uL)
LH(mIU/mL)
T (ng/dL)

Value
15.8
48.2
5.48
3.4
470

Reference

Range
13.2-17.1
38.5-50.0
4.2-5.8
1.5-9.3
241-827


Hgb “ Hemoglobin

Hct “ Hematocrit

LH “ Luteinizing Hormone

T- Total Testosterone

Laboratory values on the consultation presentation are shown in Table 2.

Table 2.

Test
Hgb (gm/dL)
Hct (%)
RBC (M/uL)
LH (mIU/mL)
T (ng/dL)

Value
18.0
60.0
6.09
<0.2
1200


Therapy was directed two-fold towards the androgen-induced polycythemia. First, the elevated Hemoglobin/Hematocrit was addressed by a therapeutic phlebotomy. Secondly, the increased rate of erythropoiesis was normalized by removing the androgen stimulus. In order to avoid the previous problematic hypogonadism upon androgen cessation a medical protocol for hypothalamic-pituitary-testicular axis (HPTA) normalization was administered.

Therapeutic phlebotomy was initiated to restore normal red blood cell indices. The approximate amount of blood volume that needed to be withdrawn to restore normal values can be calculated by the following formula. This use of the formula includes the assumption that whole blood is withdrawn. Also the duration of time over which the blood volume is withdrawn is affected by whether or not concurrent fluid replacement occurs.

CC of Blood Volume Drawn = Wt(kg) x ABV x [Hgbi - Hgbf] / [(Hgbi + Hgbf)/2]

ABV= Average Blood Volume (default = 70)

Hgbi (Hcti) = Hemoglobin initial

Hgbf (Hctf) = Hemoglobin final (desired); or

CC = 75 X 70 X [20-14]/[(20+14)/2] = 75 X 70 X (6/17) = ~1850;

@ 1Unit Whole Blood = ~350 - 450 CC; ~1850/(350 – 450) = ~4 Units

For a final hemoglobin of 14 a therapeutic phlebotomy of ~4 Units whole blood will be

required.

To return the rate of erythropoiesis to normal it is necessary to remove the androgen stimulus to erythropoietin production. In order to avoid the problematic hypogonadism mentioned previously after androgen cessation a medical protocol was administered for HPTA normalization. The protocol consisted of the medications human chorionic gonadotropin (hCG), Clomiphene citrate and Tamoxifen. Treatment takes place over two discrete intervals. The first treatment interval is to initiate the restoration of testicular function while the latter is for the coupling and restoration of the hypothalamus/pituitary and testicles.

The medications were initiated simultaneously at a time when it was expected that the body would be expected to begin endogenous testosterone production. Since the source of the exogenous androgen was depotestosterone (testosterone cypionate) with a known half-life the date to begin the medical protocol can be predicted with some accuracy. hCG 2500 U SC QOD (every other day); Clomiphene Citrate 50MG I PO BID (oral , twice a day); and Tamoxifen 20MG I PO QD (oral, once a day) were administered for 15 days. A satisfactory testosterone level on day 15, typically 350 or greater, is followed by the oral medications for an additional 15 days. This patient had a testosterone level of 423 after the initial treatment interval. Upon completion of the medications and a therapeutic phlebotomy as noted above during this period followed by a two week washout period the patient had the following laboratory values, Table 3.

Table 3.

Test
Hgb (gm/dL)
Hct (%)
RBC (M/uL)
LH (mIU/mL)
T (ng/dL)

Value
14.1
43.5
4.68
7.3
626


Discussion

This case report is not intended to oppose the use of testosterone or any androgen in the treatment/prevention of HIV associated wasting syndrome. On the contrary, these medicines have proven their worth in retaining lean body mass in HIV+ patients. Nevertheless, attention needs to be drawn to the possible complications of long-term, uninterrupted androgen usage. Toxic effects on liver function have been shown to occur from long-term oral androgen usage. While this effect of androgens is usually associated with only orally active 17-alkylated compounds, all medicines in this class have the potential to cause liver abnormalities, especially at higher dosages and long-term, uninterrupted administration. Previous research dictates that negative lipid alterations can occur almost immediately after testosterone administration. Although the suppression of HDL cholesterol by androgens is quickly reversible upon discontinuation, there is speculation as to the increased risk of cardiovascular disease while supplementing with androgens. As described in this case report, extended, uninterrupted usage of androgens can cause secondary polycythemia. Periodic discontinuation of these medicines can be beneficial to the health of the patient in terms of preventing hepatotoxicity, negative alterations in lipid profile, and polycythemia.

Patients administered androgens for muscle wasting conditions, osteoporosis, anemia, or any other disorder not associated with primary hypogonadism should be discontinued from treatment on a periodic basis to ensure safe return of testicular function and prevent side effects linked to long term, continuous usage. Conversely, in cases of primary testicular failure that does not respond to stimulation therapy, indefinite testosterone replacement without cessation may be required.

Therapies utilizing human chorionic gonadotropin and clomiphene citrate have been proposed as treatment modalities for return of testicular and pituitary function, respectively. While this treatment needs to be evaluated in more extensive controlled studies, the medical literature gives credence to the possible benefits of its use . In the case of preventing androgen induced hypogonadism, this treatment option may prove to be very valuable.

If rapid return of testicular and pituitary function post androgen treatment can be achieved, the attendant effects of androgen-induced hypogonadism (AIH); muscle atrophy, increased adiposity, depressed libido, erection dysfunction, lethargy, and depression, that are typically associated with androgen cessation may be avoided. In cases of sustained hypogonadism that can result for almost two years post therapy , progressive decrease in muscle mass, osteoporosis, oligospermia or azoospermia, and severe mood disturbances may result . Periodic discontinuation of androgen treatment would avoid possible complications due to polycythemia, liver hepatotoxicity, and suppressed HDL-C while simultaneously retaining all of the positive benefits gained during androgen therapy. It’s alarming to realize that the beneficial aspects of androgen supplementation can become transient in the face of post-therapy hypogonadism, thus making androgen therapy an insignificant treatment option if ensuing hypogonadism is disregarded. On the other hand, if androgens can be administered in short term durations to avoid associated side effects while retaining lean body mass gains post-therapy, safe and efficacious use can be applied to numerous patient populations.

References


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