Over the years I have written numerous blogs about testosterone replacement therapy (TRT) for men with clinically low testosterone (low T). I have covered topics such as the safety of TRT during Active Surveillance, what’s wrong with the old belief that high testosterone levels cause prostate cancer, and the problems when men jumped on the testosterone bandwagon.

TRT can lower sperm count

A side effect of TRT that I have not previously covered is low sperm count. A normal sperm count is 40-300 million sperm per milliliter. When natural testosterone begins to taper off due to aging, that number can decline—and with it, fertility (of course, there are notable exceptions like Mick Jagger and Steve Martin, among others). A low sperm count is considered 10-20 million sperm per milliliter, and 20 million is the lowest threshold for impregnating a woman. However, testosterone supplementation is unlikely to help. Why?

The problem has to do with how the brain’s pituitary gland registers T levels. It acts like a hormonal master control. It produces biochemical messengers (hormones), and releases them to other hormone-producing glands. Two special hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH) stimulate the testes to produce sex hormones and mature sperm. Without these messengers from the brain, the sperm “factory” is at risk for shutting down.

When natural testosterone levels decline, the pituitary responds by releasing more LH and FSH. However, when T levels are supplemented by administering manufactured T, the brain registers the increase, and the pituitary consequently reduces release of LH and FSH. Thus, a possible side effect of TRT is infertility.

A bad situation for younger men

Those hit hardest by dwindling sperm production are younger men who still want to father children. TRT use surged within 15 years of the millennium, and during that period one study found that over 12% of men on TRT were younger than 39, suggesting that a large number of men concerned about low T are in their reproductive years.^[i]

You might think that a younger man on TRT who wants to father a child scan just stop using it. However, no one knows how long it will be before he’s capable of producing at least 20 million sperm. A literature review concluded that the average probability of sperm recovery to 20 million sperm did not reach 100% until 2 years after stopping TRT, and even longer for older men with a low sperm count.^[ii] Thus, “…approaches to predicting and mitigating [lessening] the negative effects of testosterone on fertility are needed.”^[iii]

A new TRT product preserves sperm production

Now there’s good news for younger men who need TRT but still want to preserve fertility. An FDA-approved (in 2014) nasal gel called Natesto is in the late stages of a clinical trial to determine if it preserves sperm production. Unlike other TRT delivery systems that maintain high T levels around the clock, Natesto is short-acting. It is applied three times a day, and it raises T levels to help men whose low T results in ED. Because it’s short-acting, it appears to not trigger the pituitary gland to stop releasing LH and FSH.

The Phase IV study is being conducted at the University of Miami Miller School of Medicine. Lead investigator Dr. Ranjith Ramasamy states, “Our goal is to see if the gel preserves testis size and fertility, which is vital because other testosterone products cause testis atrophy and infertility.”^[iv]

So far, there is reason for optimism. If the clinical study achieves its goal, Natesto will be the first TRT product that younger men who want to want to maintain their fertility can use with confidence.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Layton JB, Li D, Meier CR, Sharpless JL et al. Testosterone Lab Testing and Initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab. 2014 Mar;99(3):835-42.
[ii] Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367:1412–1420.
[iii] Kohn TP, Louis MR, Pickett SM, Lindgren MC et al. Age and Duration of Testosterone Therapy Predict Time to Return of Sperm Count after hCG Therapy. Fertil Steril. 2017 Feb; 107(2): 351–357.e1.
[iv] https://physician-news.umiamihealth.org/nasal-gel-treats-low-testosterone-without-harming-sperm-production/