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      Frontiers in hormone therapy for male infertility

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          Abstract

          For a significant number of couples worldwide, infertility is a harsh reality. As specialists in male infertility, much of our armamentarium lacks definitive, evidence-based therapies. For years, we have relied on manipulation of the male hormonal axis to treat those men who help carry the burden of infertility in their partnerships. Indeed, male factor infertility is the sole component of infertility in at least 20% of couples. Further compounding this dilemma is that 25% to 50% of males with infertility have no identifiable etiology and thus present a true management conundrum. This manuscript is an attempt to clarify what therapies exist for the treatment of male factor infertility. We have reviewed the relevant infertility literature honing, our focus on hormonal anomalies and their subsequent impact on fertility. Many of the therapies discussed have been utilized in practice for generations. Thus, this article attempts to provide the evidence-based literature to support the continued use of the current treatment paradigm. Furthermore, we recognize that any review beckons a discussion of what challenges and therapies await on the horizon. For instance, there has been significant interest in restoring spermatogenesis after testosterone replacement therapy (TRT). We explore the adverse long-term spermatogenic outcomes associated with TRT, which with the widespread use of TRT, will inevitably present a great challenge for male infertility specialists. Moreover, we discuss the role of varicocelectomy in the treatment of hypogonadism and infertility, review the association between growth hormone (GH) and male fertility and address the challenges presented by the rising prevalence of obesity.

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          Most cited references98

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          Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men.

          To examine the relationship between body mass index (BMI) and semen quality among young men from the general population. Cross-sectional study. Danish young men were approached when they attended a compulsory physical examination to determine their fitness for military service. From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered. Semen volume (in milliliters), sperm concentration (in million per milliliter), percentage of motile spermatozoa, percentage of spermatozoa with normal morphology, total sperm count (in million), and testis size (in milliliters). In addition, serum reproductive hormones were measured. Serum T, sex hormone-binding globulin (SHBG), and inhibin B all decreased with increasing BMI, whereas free androgen index and E(2) increased with increasing BMI. Serum FSH was higher among slim men. After control for confounders, men with a BMI 25 kg/m(2) had a reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%-39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although not significantly, among men with high or low BMI. Semen volume and percentage of motile spermatozoa were not affected by BMI. High or low BMI was associated with reduced semen quality. It remains to be seen whether the increasing occurrence of obesity in the Western world may contribute to an epidemic of poor semen quality registered in some of the same countries. If so, some cases of subfertility may be preventable.
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            Obesity pandemic: causes, consequences, and solutions-but do we have the will?

            Obesity has become pandemic owing to an obesogenic environment (inexpensive calorie dense food, technologies and structure of communities that reduce or replace physical activity, and inexpensive nonphysical entertainment) and excessive emphasis on low fat intake resulting in excessive intake of simple carbohydrates and sugar. Effects are greater for women owing to their smaller size and extra weight gain with each pregnancy, with 38% of American adult women being obese. Women are responsible for more than three-fourths of the more than 400 billion dollars of excess direct health care expenditures due to obesity. They are less likely to conceive naturally and with fertility treatments, more likely to miscarry, and have more prematurity and other complications with their pregnancies. We describe the many causes, including key roles that a dysbiotic intestinal microbiome plays in metabolic derangements accompanying obesity, increased calorie absorption, and increased appetite and fat storage. Genetic causes are contributory if these other factors are present but have limited effect in isolation. The numerous health consequences of obesity are discussed. The authors itemize ways that an individual and societies can mitigate the pandemic. However, individual will power, the will of society to enact change, and willingness of the public to accept outside intervention frustrate efforts to stabilize or reverse this crisis. The most promising strategies are education and efforts by individuals to make responsible choices several times every day to protect, most effectively by prevention, their most valuable asset.
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              Loss of fertility in men with varicocele.

              To test the hypothesis that men with varicocele who have already fathered children are immune to the detrimental effect of varicocele on their fertility and will continue to be fertile. If this were the case, one would expect a very low incidence of varicocele in currently infertile men who were able to father a child in the past (secondary infertility) compared with men who have never been fertile (primary infertility). Survey of men with male factor infertility. Tertiary care university medical center. One thousand ninety-nine infertile men of whom 98 (9%) met our criteria for secondary infertility. Men with prior vasectomy and men whose partners were over age 40 were excluded. Difference in the incidence of varicocele in men with secondary infertility versus primary infertility. A varicocele was palpable in 35% (352/1,001) of men with primary infertility and 81% (79/98) of men with secondary infertility. This difference in the incidence of varicocele was highly significant. Men with secondary infertility and varicocele were slightly older (37.9 versus 33.5 years), had a lower mean sperm concentration (30.2 versus 46.1 x 10(6)/mL), more abnormally shaped sperm (72% versus 40%), and higher mean serum follicle-stimulating hormone levels (17.6 versus 7.9 mIU/mL,) compared with men with primary infertility and varicocele. The incidence of varicocele is much higher in male factor secondary infertility compared with primary infertility. These findings suggest that varicocele causes a progressive decline in fertility and that prior fertility in men with varicocele does not predict resistance to varicocele induced impairment of spermatogenesis. Men with a varicocele may benefit from early evaluation and prophylactic varicocelectomy to prevent future infertility.
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                Author and article information

                Journal
                Transl Androl Urol
                Transl Androl Urol
                TAU
                Translational Andrology and Urology
                AME Publishing Company
                2223-4691
                July 2018
                July 2018
                : 7
                : Suppl 3
                : S353-S366
                Affiliations
                [1]Department of Urology, University of Virginia Health System , Charlottesville, VA, USA
                Author notes

                Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Iyad Khourdaji, MD. Department of Urology, University of Virginia, PO Box 800422, Charlottesville, VA 22908-0422, USA. Email: akhourdaji@ 123456gmail.com .
                Article
                tau-07-S3-S353
                10.21037/tau.2018.04.03
                6087845
                265331c3-a323-4392-8b5a-7eccaa8ca735
                2018 Translational Andrology and Urology. All rights reserved.
                History
                : 29 November 2017
                : 30 March 2018
                Categories
                Review Article

                male infertility,hypogonadism,idiopathic oligospermia,azoospermia,testosterone replacement therapy (trt)

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