Vicari et al. looked at long term hCG treatment in 17 men with isolated hypogonadotropic hypogonadism, observing a significant increase in testicular volume, in a time-dependent manner, and testosterone, at 15 and 24 months of treatment (13). This corresponded with reports of symptom improvement in 50% of patients, with no reports of side effects or complications. In our study, we retrospectively evaluated 20 men who were treated for symptoms of hypogonadism with human chorionic gonadotropin (hCG) monotherapy. The major parameters of concern for analysis were T improvement from initial to follow-up as well as the degree of T changes as they correlated to dosage and other baseline characteristics such as LH, FSH and therapy duration. Dates of each patient’s treatment initiation and the latest follow-up visits were recorded to evaluate the average duration of treatment, and patient reports of side effects, complications and symptom improvement were recorded. The study also evaluated baseline characteristics such as age, treatment indications, hCG dosage, past medical history and physical exam findings. We sought to evaluate the response of serum testosterone to hCG monotherapy as evidence of its efficacy at various doses and therapeutic durations, as well as its safety. An overview of the assays available to aid in the diagnosis of testosterone deficiency is available in Table 4 (See button below). Early morning samples from each subject's most recent and previous 3 visits as well as those from 10, 15, 20, 25, and 30 years prior were analyzed (3,565 samples total with a mean of 4 samples per patient). Given these inconsistences, prevalence of low testosterone has varied dramatically among studies, with statistics reporting %.5-8 A summary of findings from four large-scale contemporary prevalence studies can be found in Table 3 (See button below). Across the prevalence literature, the cut-off values used to define low testosterone vary widely, heterogeneity exists in the populations studied, the forms of testosterone used to measure testosterone (total and/or free) are not consistent, and the assays utilized to measure testosterone differ. A review by Millar et al.4 searched MEDLINE and Embase databases from January 1966 to July 2014 for studies that compared clinical indication of low testosterone along with a measurement of serum testosterone in men. The prevalence of testosterone deficiency in the American male population is difficult to quantify. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is likely to change confidence. A total of eight patients with NOA admitted to a public fertility clinic in Denmark received gonadotropin therapy with recombinant drugs for spermatogenesis stimulation since December 2016. The primary aim of this study was to evaluate the role of recombinant gonadotropin therapy for spermatogenesis stimulation in patients with NOA due to spermatogenic failure. Early studies suggest that hCG may help boost low testosterone levels in males. In a 2020 review of several studies, researchers measured the impact of exercise on testosterone levels. Further high quality randomized controlled trials (RCTs) are necessary to help determine the extent to which hCG treatment could help prevent low testosterone levels. On average, these men experienced a 49.9% increase in testosterone levels, and 50% reported an improvement in libido, energy levels, and ED symptoms. It also considers the scientific research into whether hCG could increase testosterone levels and the risks and considerations involved. It is the opinion of this Panel that total testosterone should be tested after the commencement of therapy at a time point that allows a patient to be sufficiently established on a dosing regimen before determining if therapeutic levels have been achieved and if dosing alterations are required. Studies that randomized overweight or obese men to diet and exercise programs had significantly greater increases in total testosterone levels than men who underwent calorie reduction or exercise programs alone.378, 379 It is also postulated that men who engage in quantitatively more exercise have the greatest increases in serum testosterone from baseline.378 Until there is definitive evidence proving an association between testosterone therapy and subsequent MACE, the Panel recommends that clinicians counsel patients that the current scientific literature does not definitively demonstrate that testosterone therapy increases risk. A study by Pastuszak et al. (2015)355 found a significant increase in biochemical recurrence in high-risk patients who received testosterone therapy after RT or RT/ADT. Currently published studies have not demonstrated an increased risk of biochemical cancer recurrence in post-RP patients who are on testosterone therapy, nor does it define the optimal timing for commencement of testosterone therapy. At the end of the study, serum testosterone levels rose in those men receiving testosterone therapy; however, no rise in testosterone levels were seen within the prostate tissue itself. In addition to issues relating to the reliability of compounded products themselves, appropriate clinical studies on pharmacokinetics are lacking. In contrast to commercial pharmaceutical manufacturing, which is regulated by the FDA, compounded medications are regulated by state laws and, therefore, vary significantly from one region to another.405 While testosterone gels and creams are the most commonly used forms of compounded testosterone therapies and are routinely less expensive than branded forms of testosterone, these preparations by individual pharmacies occur without direct FDA oversight and approval. Taylor et al. reported that clomiphene citrate has outstanding biochemical and clinical efficacy, with increases in serum testosterone similar to those for testosterone gel.400 Additionally, these investigators found that clomiphene has a favorable side effect profile and is less expensive than testosterone gel.
