Treatment Overview

Treatment of hypogonadal patients aims to:

  • induce and maintain secondary sex characteristics – e.g. facial and body hair growth1,2
  • improve sexual function and libido1,2
  • induce a sense of well being, including improvement in depression scores1,3
  • optimize bone mineral density and prevent osteoporosis1,2
  • improve body weight, lean body mass, muscle mass and strength4 
     

Treatment in HIV infected men

The Endocrine Society Clinical guidelines suggest that clinicians consider short-term testosterone therapy as an adjunctive therapy in HIV-infected men with low testosterone levels and weight loss, to promote weight maintenance and gains in lean body mass and muscle strength.1



Clinical pharmacology of some testosterone formulations.

Formulation  Recommended regimen Advantages Disadvantages
Testosterone-enanthate or cypionate
  • 150–200 mg i.m. q 2 wk or 75–100 mg/wk
  • 50–100 mg i.m. every 7 to 10 days
Corrects symptoms of androgen deficiency; relatively inexpensive if self-administered; flexibility of dosing Requires i.m. injection; possible pain at injection site; peaks and troughs in serum testosterone levels; fluctuation in mood / libido; excessive erythrocytosis; coughing episodes (post-injection)
1% Testosterone gel Available in sachets, tubes and pumps, 5–10 g gel containing 50–100 mg testosterone qd Corrects symptoms of
androgen deficiency;
provides flexibility
of dosing, ease of
application, good skin
tolerability

Potential of transfer to a female partner or child by direct skin-to-skin contact; skin irritation in a small proportion of treated

men; moderately high DHT levels

Transdermal testosterone patch 1 or 2 patches, designed to nominally deliver 5–10 mg testosterone over 24 h applied qd on non-pressure areas Ease of application, corrects symptoms of androgen deficiency Skin irritation at the application site(s) occurs frequently in many
patients
Buccal,
bioadhesive,
testosterone
tablets
30 mg controlled release, bioadhesive tablets bid Corrects symptoms of androgen deficiency in healthy, hypogonadal men Gum-related adverse events in 16% of treated men; alteration in taste
Testosterone pellets 3-6 pellets implanted sc; dose and regimen vary with formulation Corrects symptoms of
androgen deficiency
Requires surgical incision for insertions; pellets may extrude spontaneously or implant site may become infected
17-α-methyl testosterone This 17-α-methylalkylated
compound should not be used because of potential for liver
toxicity
  Clinical responses are variable; potential for liver toxicity; should not be used for treatment of androgen deficiency
Oral testosterone-undecanoate 40 to 80 mg po bid or tid with meals Convenience of oral administration Variable clinical responses, variable serum testosterone levels, high DHT:testosterone ratio
Injectable long-acting
testosterone-undecanoate
in oil
European regimen 1000 mg IM, followed by 1000 mg at 6 wk,
and 1000 mg at 10–14 wk
Corrects symptoms of androgen deficiency; requires infrequent administration Requires i.m. injection of a large volume (4 ml); cough reported
immediately after injection in a very small number of men
Testosterone
in-adhesive
matrix patch
2 x 60 cm² patches delivering approximately 4.8 mg T/d Corrects symptoms of androgen deficiency; Lasts 2 days Some skin irritation

DHT = dihydrotestosterone; i.m. = intramuscular; po = per oral; sc = subcutaneous; T = testosterone
Adapted with permission from the Endocrine Society. 1

For a standalone list of medications please also see the Testosterone Replacement Therapy document 



Erectile dysfunction

Erectile dysfunction is a common finding among men with low testosterone and treatment is possible using phosphodiesterase (PDE)-5 inhibitors. However, PDE-5 inhibitors and many ARV therapies are metabolized by CYP3A4 in the liver, and so co-administration may lead to elevated levels of PDE-5 inhibitor in the blood.5,6 Therefore dose reduction/modification of the PDE-5 inhibitor may be required. Among patients with hypogonadism who are treated for erectile dysfunction, supplementation of PDE-5 inhibition with testosterone replacement may be necessary to achieve satisfactory erectile function.7



Treatment in HIV positive women

Treatment options for HIV-infected women with hypogonadism are limited. Standard hormone replacement therapy may include: 8

  • oral oestrogen (e.g. conjugated estrogen, 0.625mg/day) and progesterone (10mg/day)
  • oral contraceptive preparations
  • combination pill with estrogen and methyltestosterone (or anabolic steroid) – however this may adversely affect liver function and requires concomitant therapy with progestin in women with an intact uterus.
     



For further information please see other EMA approved medications for hypogonadism:

References

  1. Endocrine Society. Clinical Guidelines on Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes. 2010. Accessed 22 February 2011.
  2. American Association of Clinical Endocrinologists. Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients - 2002 Update. Accessed 2 July 2012.
  3. Grinspoon S, Corcoran C, Stanley T, et al. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab. 2000;85:60–65.
  4. Bhasin S, Storer TW, Javanbakht M, et al. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA. 2000;283:763–770.
  5. Merry C, Barry MG, Ryan M, et al. Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. AIDS. 1999;13:101–107.
  6. Muirhead GJ, Wulff MB, Fielding A, et al. Pharmacokinetic interactions between sildenafil and saquinavir / ritonavir. Br J Clin Pharmacol. 2000;50:99–107.
  7. Shabsigh R. Testosterone therapy in erectile dysfunction and hypogonadism. J Sex Med. 2005;2:785-792.
  8. Mylonakis E, Koutkia P, Grinspoon S. Diagnosis and treatment of androgen deficiency in human immunodeficiency virus-infected men and women. Clin Infect Dis. 2001;33:857–864.