Alternatives to testosterone replacement

Recently, a study has been published that considers testosterone restoration as an alternative to testosterone replacement. In aging male, the testosterone levels become lower but generally support sufficient testosterone levels. However, the low-normal levels of testosterone have been associated (causation not implied) with higher levels of mortality, about 35% all-cause mortality [2].

Human Corion Gonadotrophin (HCG) is a powerful hormone that can, in low doses, restore testosterone production but it has caused reduction of testicular volume and fertility parameters [1]. It has been to restore testosterone production of steroid abusers. In otherwise healthy men with low testosterone (<420 ng/dL-1) did not show expected increas in strength but caused significant reduction of testicular volume, gonadotrophin levels and, in a few cases, nipple tenderness. However, improved lean body mass was observed. Hence, long-term use of HGC therapy comes with significant side effects.

Antiestrogens such as clomiphene citrate (CC) counteracts effects of estrogens that give negative feedback to production of upstream sex hormones that promote production of testosterone [1]. Indeed, CC restored levels of follicles stimulating hormone FSH, luteinizing hormone LH and gonadotropin releasing hormone GnRH. While CC has consistently restored production of testosterone, effects on fertility and semen parameters have been variable, especially in older men were refractory to hormone manipulation while younger men had side effects of decreased libdo, lack of energy, decreased sports performance and worse mood.

Third group of anti-estrogenic treatment that aims to restore testosterone levels are aromate ihibitors AI such as anastrozole and letrozole. Since these drugs do not eliminate production of estrogens in men completely, these drugs are unlikely to cause osteoporosis in men. AI are more effective in raising testosterone levels than transdermal forms of testosterone such as testosterone gel [1]. The side effects of AI are minimal, mainly limited to unalarmingly modest increase of prostate specific antigen PSA (biomolecule used assess prostate pathology).

Fourth group is SARMs [3] or selective androgen receptor modulators such as ostarine, a “field leader”. Ostarine support smuscle growth and does not affect or even suppresse prostate growth, and does not significantly suppressing endogenous androgen production in clinically used doses. However, the selectivity of SARMs is not absolute, potency and selectivity appears to be a trade-off. A potent SARM such as ligandrol suppresses endogenous testosterone and also high density cholesterol – these side effects resembe side effects anabolic steroids [4]. SARMS can be expected to have cognition preserving results, some very low (cell culture) level studies with SARMS such as RAD-140 and NEP20 appear to support the theory [5,6].

Finally, some herbal medicines can improve aspects of androgen deficiency. Tribulus terrestris has been reviewed thorouhghly but with mainly positive effects in focus [7]. T. terrestris increases sex drive, appears to have properties that protect heart and blood vessels as well as nervous system from insults, has anti-inflammatory properties. Hovever, the abilities of tribulus terrestris to inreace endurance in rodents could not be replicated in controlled studies with human subjects [8,9]. Eurycoma longifolia is a herbal supplement with respectable traditional use with drawback of relatively high price, widespread distribution of fake extracts, and low bioavailability (10%) of main constituent eurycomanone (tested in rodents). Eurycoma longifolia has been reviewed comprehensively, and it has been tested in humans, mostly in association with aphrodisiac properties[10]. While E. longifolia has not been to subject of thorough exercise research, it seems to modestly improve testosterone levels, fertility parameters and libido on men with late onset hypogonadism, with additional benefits of being anti-diabetic, promoting bone strength and reducing anxiety.