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Hypogonadism in men is primarily a state involving lower than expected levels of testosterone. Traditionally, the condition has been treated almost exclusively with testosterone supplementation. However, low testosterone can be fairly complex, involving a myriad of factors including the inability of the testes to produce sufficient testosterone, improper brain signaling and excess estrogen.
Primarily seen as female hormones, estrogens are also very important in men since declining testosterone can alter the androgen:estrogen (T:E2) relationship. While there is not an established target value, changes in the T:E2 ratio can result in complications such as declining prostate health.1
In some men, clear reasons behind low testosterone can be difficult to determine. The consequences, however, can be the same: insufficient testosterone that results in an unhealthy life, often characterized by symptoms such as loss of libido, erectile dysfunction, hair loss, depressed mood and lethargy. After proper diagnosis, including testing for testosterone, estrogen and luteinizing hormone (LH), properly directed therapy might dramatically reverse these symptoms and provide a healthier, more robust lifestyle.
For many men, the simplest and least invasive ways to reduce estrogen levels are to lose weight, replace fatty diets with low-fat alternatives and engage in regular exercise. This is because aromatase, an enzyme responsible for converting testosterone to estradiol (as well as converting androstenedione to estrone) is more abundant in adipose tissue. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes.2
Three specific nutrients appear to be particularly useful in elevating low testosterone: magnesium, vitamin D and zinc. Magnesium supplementation was shown to increase free and total testosterone, with even higher increases in men who supplemented magnesium and exercised regularly.3 Additionally, a study showed an association between vitamin D levels and testosterone levels (i.e., men who had low vitamin D levels frequently also had low levels of testosterone).4 And lastly, a study proved low zinc levels correlated with low testosterone levels; restoration of the zinc deficiencies restored testosterone levels.5
Wellness Works recently launched nutritional supplements specifically designed to support men’s health. Nutritional supplements include Men’s Complete Whole Food Multi, Male Virility Support and Prostate Health Support.
For many men, testosterone supplementation is the treatment of choice — it is easily understood and, when properly administered, can be very effective in boosting testosterone levels. However, a decrease in sperm production is common in testosterone supplementation. Therefore, in men who wish to maintain their fertility and testicular size, options to boost testosterone production, rather than supplementation itself, should be considered.
Topical administration appears to be the most effective way of dosing testosterone. While creams, solutions and lotions have been used, over the past dozen years the greatest benefit seems to come from topical gels.
Testosterone is a lipophilic steroid hormone and is absorbed well in topical preparations. The delivery system, however, absolutely makes a difference. An alcohol-free compounding base, such as Atrevis Hydrogel®, eliminates the possibility of skin irritation. In addition, alcohol evaporates, which causes the concentration of the gel to change and may cause variations in dosage. Atrevis is a water-based gel with specific penetration enhancers that help drive the testosterone through skin. The skin-permeation enhancers, one of which is patented, improve the solubility and dispersibility of testosterone, making it easier to be absorbed.
Daily topical dosing with testosterone in Atrevis helps maintain steady-state levels: The patient will likely not have the peak-and-valley experience that is common with testosterone injections. I suggest starting with 50 mg topically in Atrevis with an expected topical dose range of 40–120 mg daily. Transfer to a child or female is a risk of topical dosing and every precaution should be taken to mitigate that risk.
Members with clinical services access may contact our Clinical Services team for help with compounding preparations for low testosterone levels in men and other compounding concerns.
This Blog is a compilation of several PCCA Documents (#99637, #99533, #99198, #98474 and #97028) authored by retired PCCA Clinical Compounding Pharmacist Bruce Biundo, RPh, FACA, and reviewed by Sara Hover, RPh, FAARM, PCCA Clinical Services Manager. Members may access these and other documents at Members-Only Website > Documents.
Everyone is invited to listen to The Mortar & Pestle podcast, “Men’s Health: Testosterone with Bruce Biundo,” broadcasted on August 17, 2023, where Bruce discusses new major studies — including the TRAVERSE Study that reviews testosterone and cardiovascular risk. You can also access the podcast on your device using your favored podcast application.