After menstruation begins, FSH levels decrease due to estrogen's negative feedback and inhibin B produced by the developing follicle. In the era of rising testosterone use and greater awareness of AAS use in younger men, clinicians need to be aware of the detrimental effects of these agents on spermatogenesis. Such a scenario is difficult because the current status of his spermatogenesis may be deduced only by careful history, testis volume on clinical exam, and serum hormone testing of the HPG axis. The newer SERM on the horizon, EC, has been studied in the phase II clinical trial setting specifically demonstrating preservation of spermatogenesis on semen analysis while satisfactorily improving hypogonadal symptoms and serum testosterone levels, and phase III data is pending.82,84 Finally, AIs such as anastrozole or letrozole may be helpful in this clinical scenario for patients who are obese and/or exhibit a low T/E ratio HCG has proven to maintain ITT levels with doses as low as 500 IU every other day.56,57 Clinical data evaluating higher doses of hCG given as monotherapy (500–2500 IU twice weekly), or low-dose hCG (500 IU every other day) in combination with TRT, have demonstrated satisfactory results for maintaining spermatogenesis,57,58 and either would be a good choice as recommended by these authors. Therefore, aromatase inhibition in men can result in decreased estrogen levels and ultimately increased gonadotropin production. Alternatively, the same data demonstrate a median time to recovery of 20 × 106 ml-1 sperm ranging from 3 to 6 months, with probability estimates suggesting recovery in 67%, 90%, 96%, and 100% of men at 6, 12, 16, and 24 months, respectively, after discontinuation of testosterone exposure.13 These data also suggest that a longer exposure to exogenous testosterone, Asian ethnicity, and older age may result in a prolonged recovery time after treatment cessation.13,30,31,32 Importantly, one must consider that these data are carefully collected in men within the tightly controlled, clinical trial environment, and may not be generalizable.
Data specifically evaluating induction or maintenance of spermatogenesis in men with HH and azoospermia specifically due to previous TRT and/or AAS use is scarce (Table 2). Most experts treat with hCG alone for 3–6 months after which a certain number of cases will result in spermatogenesis induction. Therefore, men with azoospermia or severe spermatogenic defects due to classic HH serves as a useful context in whom to appreciate the effect of gonadotropins upon spermatogenesis clinically. To date, direct comparisons between the two have not occurred for use at inducing spermatogenesis in men, but data from use in women suggest that rFSH is equivalent to urinary preparations and can avoid the theoretical risk of Creutzfeld–Jakob disease;38,40 therefore, rFSH is the preferred method of pharmacologic delivery of FSH in men.
Estrogen forms a negative feedback loop by inhibiting the production of GnRH in the hypothalamus. In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle and ovarian cycle. Continuous secretion of GnRH uncouples the gonads from pituitary regulation and leads to decreased synthesis of gonadotropins and hypogonadism. The pulsatile release of GnRH by hypothalamic neurons is necessary for adequate gonadotropin production by the pituitary.
This suppression results in changes to the pulsatile release of GnRH from the hypothalamus, reverting the LH secretion pattern to pre-pubertal levels. In anorexia nervosa, severe caloric restriction and subsequent weight loss lead to a suppression of the HPG axis. For example, women with eating disorders tend to have oligomenorrhea (prolonged menstrual cycles greater than 35 days) and secondary amenorrhea (absence of menstruation for at least three consecutive months). The HPG axis can also be suppressed by GnRH antagonists or continuous administration of GnRH agonist, such as in the following applications Also as a result, many of the side effects are similar to the symptoms of pregnancy. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. For example, the male mutation of the GnRH coding gene could result in hypogonadotrophic hypogonadism.
Since HCG mimics LH, the goal is for the body’s LH to take over communicating with the testicles to maintain volume and adequate testosterone production. While symptom relief is important, true hormone optimization means protecting the broader system that regulates testosterone production. The hypothalamic-pituitary-testicular axis (HPTA) is your body’s natural hormone signaling system. It involves a gradual reduction in the dosage of TRT, combined with the use of certain medications and supplements to support the body’s natural testosterone production. Research has shown that HPTA restart protocol can be effective in helping the body resume normal testosterone production after discontinuing TRT. To support the body’s natural testosterone production during this time, individuals may be prescribed medications such as clomiphene citrate (CC) or tamoxifen citrate (Nolvadex).