Low T without elevated gonadotropins

TV advertising for ‘Low T’ (testosterone) has brought a spate of new patients to the clinic. Their ages range from the mid-20s to older than 70 years; most of the older patients also have type 2 diabetes; and many are substantially overweight.

After obtaining a history and completing a physical examination, I introduce the patient to the ADAM test, a straightforward set of 10 questions that Morley and colleagues demonstrated have a significant predictive value for male hypogonadism. The lab screening includes measurement of free and total testosterone, gonadotropins (luteinizing and follicle-stimulating hormones) and prolactin. Bioavailable testosterone and sex hormone-binding globulin (SHBG) are supplementary lab tests that may provide clarification.

The majority of the older, obese patients with and without diabetes with laboratory confirmed hypogonadism do not have elevated prolactin or gonadotropins. Why? I have searched long and hard on PubMed and have not yet found a satisfactory explanation. The two review articles below (one a rat model, one a study in humans) are the closest I could get. There is also an “association” between ghrelin and other receptors and hypogonadism in obese men with and without diabetes, but none of the articles I perused provided more than speculation in humans. Hopefully some of the readers of this blog can educate me.

An elevated serum prolactin is uncommon in older (anyone 10 or more years older than you or I!), obese men with or without diabetes. This is seen more often, but not frequently, in younger men with low testosterone and low gonadotropins. The management is straightforward — evaluate and treat the prolactinoma.

Low testosterone with elevated gonadotropins is also straightforward to treat — replace the testosterone. There are several options for treating patients with low testosterone and normal prolactin, but low gonadotropins. “Older” men with these results should receive testosterone, as should younger men who have had a vasectomy. Read Tom Repas’ excellent blog on this topic posted a few weeks ago.

In younger men with hypogonadotropic hypogonadism who may wish to father a child in the future, testosterone replacement would rob them of that opportunity. Increasing testosterone levels, particularly free and bioavailable, can be accomplished in most of them by administration of chorionic gonadotropin or clomiphene citrate. Unfortunately, while my crib sheets tell me that they may be covered by insurance and may have a low co-pay, getting these therapies approved for the patient is cumbersome, to put it mildly. That is not an excuse for not being persistent, and I try hard to practice anger management waiting days and sometimes weeks to get through to someone who will listen rather than put my support staff on hold for several minutes before transferring them to the next person with the same approach.

For more information:

Dandona P. Curr Mol Med. 2008;8:816-828.
Mah PM, Wittert GA. Mol Cell Endocrinol. 2010;316:180-186.
Morley JE. Metabolism. 2000; 49:1239-1242.