Diagnosis and treatment of hypogonadism in men seeking to preserve fertility

madman

Super Moderator
Male hypogonadism is a clinical syndrome that results in low testosterone levels and frequently leads to infertility. The syndrome occurs due to disruption at one or more levels of the hypothalamic-pituitary-gonadal axis. Testosterone replacement therapy (TRT)is the most common treatment utilised for male hypogonadism. However, long-acting forms of TRT leads to infertility and so is inappropriate for patients wishing to conceive. For patients who wish to remain fertile, nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone and aromatase inhibitors have been used as alternative treatment options with different degrees of success. A review of the literature was performed to identify the safety and efficacy of alternative treatment options. Gonadotropin releasing hormone can successfully induce spermatogenesis but is impractical to administer. Likewise,aromatase inhibitors have limited use due to inducing osteopenia. Nasal TRT may be a good treatment option for these patients,but its efficacy has so far only been demonstrated in small sample sizes. However, clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control and can successfully induce fertility in hypogonadism patients.




*TESTOSTERONE REPLACEMENT THERAPY


*ALTERNATIVE TREATMENT OPTIONS





As discussed above some patients may have a reversible cause of their hypogonadism. This can include obesity, medications, and chronic disease. For these patients further pharmacological intervention may be unnecessary and conservative measures should be trialled. Weight loss significantly increases testosterone levels [60, 61]. While the effect is greatest for patients classified as obese by body mass index a significant increase is still seen in those who are overweight [60]. Medications such as opioids are known to cause hypogonadism [8, 62, 63]. A medications review should therefore be undertaken, and any possibly suppressing testosterone production should be stopped if possible or given at the lowest therapeutic dose. Better management of chronic diseases may also be valuable but there is limited evidence on this topic. Type two diabetes is linked to reduced testosterone levels [64]. For these patients tighter glycaemic control may increase testosterone levels. Moreover, all hypogonadism patients should be encouraged to lead a healthy lifestyle. Weight loss, exercise and smoking cessation all increase fertility [65].





CONCLUSION

The most common treatment for male hypogonadism is TRT. While long-acting TRT is effective it can lead to infertility and so is not advised for hypogonadal men wishing to maintain their fertility. For this group of patients, different treatments are required. Two of the alternative options, GnRH and aromatase inhibitors, appear to have limited use. Aromatase inhibitors decrease bone density and GnRH is impractical to administer. Nasal formulations of TRT appear to promote spermatogenesis but this has only been demonstrated in small cohorts and with short follow up. Therefore, while nasal TRT may be a good alternative further research is required to ensure its efficacy and safety. However, CC and gonadotropin therapy are viable alternatives. Both induce spermatogenesis and appear to be safe. In addition to pharmacological intervention, the patient’s general health should be optimised to maximise the chances of conception.




Table 1. Subcategories of hypogonadism with typical gonadotrophin levels.
Screenshot (35446).png





Table 2. A summary of the different treatment alternatives to TRT for hypogonadal men wishing to maintain fertility.
Screenshot (35447).png
 

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Predict estradiol, DHT, and free testosterone levels based on total testosterone

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This tool provides predictions based on statistical models and should NOT replace professional medical advice. Always consult with your healthcare provider before making any changes to your TRT protocol.

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Understanding Your Hormones

Estradiol (E2)

A form of estrogen produced from testosterone. Important for bone health, mood, and libido. Too high can cause side effects; too low can affect well-being.

DHT

Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth, prostate health, and masculinization effects.

Free Testosterone

The biologically active form of testosterone not bound to proteins. Directly available for cellular uptake and biological effects.

Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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