One well established characteristic of PWS is altered development and function of reproductive systems. This can include hypogonadism; under-development of sexual organs, particularly the testes in males; precocious puberty; and infertility.
Of these, hypogonadism, or the production of little to no hormones (e.g. testosterone and estrogen) by reproductive organs, is of particular concern because testosterone plays such an important role in body fat composition as well as development and maintenance of bone and muscle mass. Many reports suggest that hypogonadism is one of the contributing factors to obesity and osteoporosis in PWS, suggesting that patients may realize benefit from hormone replacement therapy. Importantly, there are numerous questions surrounding the potential use of hormone replacement therapy in PWS. A recent study published in the American Journal of Medical Genetics [Testosterone Replacement Therapy to Improve Secondary Sexual Characteristics and Body Composition Without Adverse Behavioral Problems in Adult Male Patients With Prader–Willi Syndrome: An Observational Study] is a significant step towards a better understanding of the potential therapeutic benefits of testosterone replacement therapy (TRT) in adult males with PWS. This study involved 22 males (ages 16-48) with hypogonadism who underwent monthly TRT over a period of two years.
Results from the study showed an ~8% decrease in body fat accompanied by significant improvements in bone mineral density and lean body mass. Increased pubic and body hair was observed in more than 70% of participants. Sexual function also developed in a small percentage of participants, although sperm were not detected in three samples tested. One of the main concerns over TRT in adult males with PWS is the worsening, or onset, of aggressive behavior problems, similar to the side effects of steroid use in athletes. Very promising, the researchers in this study did not see a significant increase in aggressive behavior as determined by the MOAS (modified overt aggression scale) assessment. However, it is important to note that the study group was relatively limited in scope. Only one participant was UPD, only one had previously received GH therapy, and the study excluded any participants with existing severe behavior problems.
Additional clinical studies are needed to determine if TRT is an appropriate and effective therapy for improving obesity and osteoporosis in PWS, but this study provides a sound basis for continuing to study this option. A critical question is how TRT works in conjunction with GH. We would encourage additional research in this area, ultimately leading to the development of consensus guidelines for the use of TRT in adult males PWS.
Finally, for those interested in evaluating TRT for their loved one with PWS, it should be noted that although this study used monthly injectable testosterone, there are other methods of delivery, including gels and patches. Those options may have advantages as they may result in more steady levels of testosterone over time, which might be better for maintaing an even keel with respect to mood and behavior. Be sure to fully discuss all options with your health care provider.