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secondary hypogonadism treatment
Jun 12, 2011

Hello Dr. I have a question: I am currently HIV patients CD4 values ââ450 and viral load below 20 copies, my treatment is Epzicom and raltegravir. I was recently diagnosed with hypogonadotropic hypogonadism (low levels of FSH, LH, testosterone, and SHBG). (secondary hypogonadism) the endocrinologist (not know that I am HIV positive), he prescribed a treatment to increase my level of testosterone with aromatase inhibitors (letrozole 2mg every other day). we recommend this hormone for HIV-positive patients with hypogonadotropic hypogonadism?, as I have understood that antiretroviral drugs can cause decreased bone?, aromatase inhibitors are synthesized in the cytochrome P450, will have a negative interaction?, who recommended me? ?

Response from Mr. Vergel

Letrozole (Femara) is the chemical name of Novartis selective third generation aromatase inhibitor. Other older aromatase inhibitors include Arimidex (anastrazole), Clomid (clomiphe) and Nolvadex (tamoxifen). Letrozole has a stonger afinity to the estrogen receptor than the other two other drugs.

While testosterone replacement is the most commonly used treatment for testosterone deficiency, it can lead to decreased sperm count and possible infertility (more on this later). It may be a less effective physiologic therapy for patients with secondary hypogonadism due to pituitary dysfunction. Clomiphene and letrozole are believed by some to allow for restoration of testicular function by restoring physiologic pituitary function in some men with hypogonadism (this statement has not been proven in clinical studies). Both have been know to increase LH and testosterone. It does not appear to downregulate testicular Leydig cell activity, because it blocks testicular estrogen receptors.

Letrozole's mechanism of action is primarily as an "antiestrogen." It occupies estrogen receptors and "deceives" the hypothalamus into sensing a low estrogen environment. This activity enhances the hypothalamus' release of GnRH, which impacts the HPGA by stimulating release of FSH and LH from the pituitary. It may provide an approach to hormone replacement that is more similar to the normal physiology compared with testosterone replacement therapy, and it may preserve fertility. Further study will be needed to clarify the compound's potential utility in this indication.

I would be careful not to lower your estradiol levels too low (I am sure your doctor will check them) because optimum estradiol is needed for bone and hair health, and sexual function. Also, ensure that your LH and free testosterone do not go up to levels higher than normal. Dose reduction will be required.

You may want to read these two studies:

Letrozole Versus Testosterone. A Single-Center Pilot Study of HIV-Infected Men Who Have Sex with Men on Highly Active Anti-Retroviral Therapy (HAART) with Hypoactive Sexual Desire Disorder and Raised Estradiol Levels

Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism

I am really curious about this drug's effect on sexual function, so please let us know what your experience is after you use it for a few weeks.

Nelson



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