Systematic review of hormone replacement therapy in the infertile man

Meliegy, Amr El; Motawi, Ahmad; Salam, Mohamed Ahmed Abd El

doi:10.1016/j.aju.2017.11.011

Cited by 21 publications

(20 citation statements)

References 60 publications

(62 reference statements)

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“…When designing a treatment plan for TRT in young adults, clinicians must understand that most exogenous T therapy will suppress spermatogenesis and decrease fertility potential (36,37). As such, identifying modifiable risk factors that may lead to hypogonadism should be an early step in patient evaluation as correction of many of the aforementioned conditions may mitigate the need for TRT.…”

Section: Treatment Options For Adolescent and Young Adulthood Men With mentioning

confidence: 99%

Low Testosterone in Adolescents & Young Adults

et al. 2020

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Male hypogonadism, the clinical syndrome with variable symptoms associated with gonadal dysfunction, can affect men of all ages. In older males, physiologic changes of the aging testis, account for the majority of decreased testosterone levels in this population. For younger males and adolescents, the etiology of hypogonadism is commonly due to congenital or acquired conditions that disrupt the testis production of testosterone or signaling from the hypothalamic-pituitary-gonadal axis. Diagnosis of hypogonadism in younger males can be a challenge, as symptoms such as decreased libido or erectile dysfunction, common in the older men, are not usually present, and young men instead commonly complain of low energy. While an underlying congenital cause should always be considered in young men with hypogonadism, acquired conditions such as obesity, diabetes, anabolic steroid or illicit drug use have all been associated with low testosterone levels. Outside of modifying identifiable risk factors for hypogonadism, pharmacologic testosterone therapy can also lead to therapeutic dilemmas in young men who desire paternity. Topical or injectable administration of testosterone, through negative feedback on the hypothalamus and pituitary, can decrease spermatogenesis, posing an infertility risk. Other agents that can replace testosterone or increase the body's natural production of testosterone without decreasing spermatogenesis are preferred, such as intranasal testosterone, selective estrogen modulators, aromatase inhibitors or human-chorionic gonadotrophin, often used in combination. Clinicians must maintain a high level of suspicion to properly diagnose young men with hypogonadism and tailor treatment based on both the underlying etiology and fertility goals.

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Section: Treatment Options For Adolescent and Young Adulthood Men With mentioning

confidence: 99%

Low Testosterone in Adolescents & Young Adults

et al. 2020

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“…It has been established that SERMs, such as CC, should be considered as a treatment option for hypogonadal, infertile men. Such treatment has been found to be effective, have minimal side effects/complications, and low cost (Patankar et al 2007;Chua et al 2013;Chehab et al 2015;Usadi and Merriam 2015;El Meliegy et al 2017;Wheeler et al 2019). Notably, an optimal CC dose has not been established, with dosing recommendations ranging from 12.5 to 400 mg per day (Chehab et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Clomiphene citrate improved testosterone and sperm concentration in hypogonadal males

Delu

Kiltz²,

Kuznetsov

et al. 2020

Systems Biology in Reproductive Medicine

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When considering empirical medical management (EMT) options for men with unexplained infertility (UI), clomiphene citrate (CC) has been shown to positively influence sperm parameters in hypogonadal men. Unfortunately, the optimal cut point for defining hypogonadism for this patient population has not been established. We hypothesized that hypogonadal men with UI having the lowest serum total testosterone (TT) (<265 ng/dL) would have a significant post-CC improvement in both TT and semen characteristics compared to those in the TT > 264 ng/dL group. We performed our study based on an IRB-approved retrospective chart review of 83 males with UI receiving more than 90 days of 50 mg daily CC. Serum TT and semen characteristics were studied in 83 patients before and in 23 patients after CC treatment. Median TT level increased from 256 ng/dL to 630 ng/dL (p < 0.001, n = 83) and SC increased from 6 (10 6 /ml) to 20 (10 6 /ml) (p < 0.016, n = 23). Overall, our results demonstrated the following: (1) CC treatment at all currently used serum TT cut-points resulted in significant improvement in both TT (p < 0.001) and sperm concentration (p = 0.03). No significant change in post-CC sperm motility or morphology was noted. (2) Correlation and linear regression analyses demonstrated that CC treatment significantly increased TT in 96% (22 of 23) of patients, and (3) when grouped as two cohorts (≤264 and >264 ng/dL), sperm concentration and TT improved 2.3 to 2.6-fold (p < 0.001) and 1.45 to 2.5-fold (p < 0.01) respectively. Thus, for hypogonadal men with UI, CC significantly improved TT and sperm concentration regardless of pre-treatment, baseline serum TT level. For this reason, CC treatment should be considered in men with UI having a TT < 400 ng/dL.

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“…Inability for normal responses to pregnancy may affect a woman's ability to conceive or to successfully carry a pregnancy to term. In addition, men who develop hypogonadism and low testosterone also face challenges with reproductive fitness, as exogenous testosterone inhibits spermatogenesis . It is speculated that PD1 plays a role in the maintenance of pregnancy, and single‐nucleotide sequence variants of the PD1 gene have been identified in women with recurrent pregnancy loss .…”

Section: Choice Of Adjuvant Therapy—safety Considerationsmentioning

confidence: 99%

“…In addition, men who develop hypogonadism and low testosterone also face challenges with reproductive fitness, as exogenous testosterone inhibits spermatogenesis. 36 It is speculated that PD1 plays a role in the maintenance of pregnancy, 37,38 and single-nucleotide sequence variants of the PD1 gene have been identified in women with recurrent pregnancy loss. 39 Long-term fertility studies after therapy are lacking because of the brief duration of clinical use of these agents.…”

Section: Choice Of Adjuvant Therapy-safety Considerationsmentioning

confidence: 99%

Considering adjuvant therapy for stage II melanoma

Poklepovic

Luke

2019

Cancer

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Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier stage at diagnosis. Before 2011, treatment options were limited for patients with metastatic disease, and the median overall survival was less than 1 year. Since then, the field of melanoma therapeutics has undergone major changes. The use of anti–CTLA‐4 and anti‐PD1 immune checkpoint inhibitors and combination BRAF/MEK inhibitors for patients with BRAF V600 mutations has significantly extended survival and allowed some patients to remain in durable disease remission off therapy. It has now been confirmed that these classes of agents have a benefit for patients with stage III melanoma after surgical resection, and anti‐PD1 and BRAF/MEK inhibitors are standards of care in this setting. Some patients with stage II disease (lymph node‐negative; American Joint Committee on Cancer stage IIB and IIC) have worse melanoma‐specific survival relative to some patients with stage III disease. Given these results, expanding the population of patients who are considered for adjuvant therapy to include those with stage II melanoma has become a priority, and randomized phase 3 clinical trials are underway. Moving into the future, the validation of patient risk‐stratification and treatment‐benefit prediction models will be important to improve the number needed to treat and limit exposure to toxicity in the large population of patients with early stage melanoma.

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Systematic review of hormone replacement therapy in the infertile man

Cited by 21 publications

References 60 publications

Low Testosterone in Adolescents & Young Adults

Low Testosterone in Adolescents & Young Adults

Clomiphene citrate improved testosterone and sperm concentration in hypogonadal males

Considering adjuvant therapy for stage II melanoma

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