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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
How loong until sperm production is impacted?
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<blockquote data-quote="madman" data-source="post: 198583" data-attributes="member: 13851"><p>Have you had a semen analysis done as this is critical?</p><p></p><p></p><p><strong>*<u>Sensibly, all men wishing to preserve fertility while on TTh should obtain a baseline SA</u>. <u>During the initial consultation, it is also important to identify the patient’s goals with regard to the timing of the pregnancy (Table 1)</u>.</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>MECHANISMS OF ACTION </strong></p><p></p><p>1. Testosterone</p><p></p><p></p><p><em><u>Testosterone is synthesized by the Leydig cells of the testes as the end product of an elegant series of hormonal interactions known collectively as the HPG axis</u> [21].</em> The hypothalamus, located in the forebrain, secretes gonadotropin-releasing hormone in a pulsatile fashion which then travels via the hypophyseal-portal system to reach the anterior pituitary [22].<em> <u>In response to this stimulus, the anterior pituitary secretes both FSH and LH. FSH acts on the Sertoli cells of the testes in order to facilitate spermatogenesis while LH acts on Leydig cells stimulate testosterone production</u>. <u>This results in impressively high intra-testicular concentrations of testosterone that are essential for sperm production and approximately ~×40 serum levels </u>[16].</em> <em>The remainder of testosterone is released systemically and exerts the physiologic effects detailed above.</em></p><p><em></em></p><p><em><u>Exogenous testosterone’s deleterious effects on male reproduction stem from its disruption of the above-described male HPG axis and the resulting decreases in both serum FSH and LH</u> [23]. <u>Without appropriate stimulation from FSH, Sertoli cells become incapable of supporting spermatogenesis while sub-par levels of LH leads to decreased production of endogenous testosterone from Leydig cells</u>.</em> <em><u>Although serum testosterone levels are maintained with exogenous administration, appropriate intra-testicular levels of testosterone can only be achieved by endogenous production and are essential for normal spermatogenesis</u> [16]. Consequently, exogenous testosterone almost universally leads to low intra-testicular testosterone with resulting atrophy of the germinal epithelium and subsequent azoospermia in upwards of 40% of men [24]. Although most men will eventually experience a return of sperm to the ejaculate following cessation of testosterone use, complete restoration of prior fertility is uncertain [25,26]. Even with adjunctive therapy, up to 30% of previously azoospermic men may fail to achieve total motile counts greater than 5 million [25].</em></p><p></p><p></p><p></p><p></p><p><strong>MAINTENANCE OF FERTILITY WITH CONCURRENT TESTOSTERONE USE</strong></p><p></p><p><em>Preserving testicular function and reproductive ability remains an ongoing challenge to practitioners prescribing TTh. Exogenous testosterone is known to decrease intratesticular testosterone and thus impair spermatogenesis.</em> <em>Indeed, in 1996 the World Health organization investigated weekly injections of 200 mg testosterone enanthate (TE) as a form of contraception. The task force demonstrated that TE caused azoospermia in approximately 75% of men after only 6 months of use [71]. Both the American Urological Association and the Endocrine Society published guidelines in 2018 which recommend against TTh in men wishing to preserve fertility [2,72].</em> <em><u>Current evidence suggests, however, that adjuvant medications can be prescribed in an effort to maintain testicular health and fertility while receiving TTh</u>.</em></p><p><em></em></p><p><em><u>Coadministration of HCG with TTh has been shown to help preserve spermatogenesis in men by maintaining physiologic intratesticular testosterone levels throughout treatment</u>. In 2005, Coviello et al [58] demonstrated that TTh caused intratesticular testosterone levels to drop by 94% in otherwise healthy, reproductive-aged men. However, adding subcutaneous 250 IU HCG every other day to their TTh regimen prevented this precipitous fall with intratesticular testosterone levels only dropping 7% from baseline. Furthermore, men who received TTh and 500 IU of HCG every other day actually experienced an increase in their intratesticular testosterone by 26% [58]. <u>This study showed that intratesticular testosterone could be reliably maintained while on TTh</u>. Future studies would prove that spermatogenesis itself, and thus the male’s fertility, could likewise be persevered throughout therapy</em></p><p><em></em></p><p><em><u>A retrospective study published by Hsieh et al [73] in 2013 found that out of 26 men treated with TRT and intramuscular 500 IU HCG every other day, no patient became azoospermic</u>. Nineteen of the 26 patients received injectable testosterone while seven were treated with transdermal testosterone gels. Mean serum hormone levels before vs during treatment were: testosterone 207.2 vs. 1,055.5 ng/dL (p<0.0001), free testosterone 8.1 vs. 20.4 pg/mL (p=0.02). No differences in SA parameters were observed during greater than 1 year of follow-up. During the study’s follow-up, nine men established a pregnancy with their partner [73].</em> <em><u>This study continues to serve as the foundation of ‘fertility-preserving TTh regimens currently utilized today</u>.</em></p><p><em></em></p><p><em><strong>*<u>Sensibly, all men wishing to preserve fertility while on TTh should obtain a baseline SA</u>. <u>During the initial consultation, it is also important to identify the patient’s goals with regard to the timing of the pregnancy (Table 1)</u>.</strong></em></p><p></p><p></p><p><strong>Table 1. Summary of recommendations for maintenance of spermatogenesis with TTh or AAS use</strong></p><p>[ATTACH=full]13570[/ATTACH]</p><p></p><p></p><p></p><p></p><p><strong>CONCLUSIONS</strong></p><p></p><p><em>Initiating testosterone replacement therapy requires an open and honest discussion between the physician and patient. The risks, benefits, alternatives, and expectations must be reviewed in detail with a specific focus on the reproductive implications involved with treatment. While many side effects of TTh such as cardiovascular impact remain surrounded by controversy, the findings of decreased intratesticular testosterone and subsequent impaired sperm production are well-documented. <u>Fortunately, the aforementioned maneuvers show promise in maintaining testicular health throughout treatment while facilitating the successful restoration of fertility when trying for pregnancy. CC and HCG both play pivotal roles in helping to restore spermatogenesis in these men</u>. Further randomized, prospective studies are necessary to elucidate the most effective treatment programs both during and after TTh. <u>In the meantime, men considering TTh who are interested in preserving fertility should be treated by experts familiar with the intricacies of these medication regimens</u>.</em></p></blockquote><p></p>
[QUOTE="madman, post: 198583, member: 13851"] Have you had a semen analysis done as this is critical? [B]*[U]Sensibly, all men wishing to preserve fertility while on TTh should obtain a baseline SA[/U]. [U]During the initial consultation, it is also important to identify the patient’s goals with regard to the timing of the pregnancy (Table 1)[/U]. MECHANISMS OF ACTION [/B] 1. Testosterone [I][U]Testosterone is synthesized by the Leydig cells of the testes as the end product of an elegant series of hormonal interactions known collectively as the HPG axis[/U] [21].[/I] The hypothalamus, located in the forebrain, secretes gonadotropin-releasing hormone in a pulsatile fashion which then travels via the hypophyseal-portal system to reach the anterior pituitary [22].[I] [U]In response to this stimulus, the anterior pituitary secretes both FSH and LH. FSH acts on the Sertoli cells of the testes in order to facilitate spermatogenesis while LH acts on Leydig cells stimulate testosterone production[/U]. [U]This results in impressively high intra-testicular concentrations of testosterone that are essential for sperm production and approximately ~×40 serum levels [/U][16].[/I] [I]The remainder of testosterone is released systemically and exerts the physiologic effects detailed above. [U]Exogenous testosterone’s deleterious effects on male reproduction stem from its disruption of the above-described male HPG axis and the resulting decreases in both serum FSH and LH[/U] [23]. [U]Without appropriate stimulation from FSH, Sertoli cells become incapable of supporting spermatogenesis while sub-par levels of LH leads to decreased production of endogenous testosterone from Leydig cells[/U].[/I] [I][U]Although serum testosterone levels are maintained with exogenous administration, appropriate intra-testicular levels of testosterone can only be achieved by endogenous production and are essential for normal spermatogenesis[/U] [16]. Consequently, exogenous testosterone almost universally leads to low intra-testicular testosterone with resulting atrophy of the germinal epithelium and subsequent azoospermia in upwards of 40% of men [24]. Although most men will eventually experience a return of sperm to the ejaculate following cessation of testosterone use, complete restoration of prior fertility is uncertain [25,26]. Even with adjunctive therapy, up to 30% of previously azoospermic men may fail to achieve total motile counts greater than 5 million [25].[/I] [B]MAINTENANCE OF FERTILITY WITH CONCURRENT TESTOSTERONE USE[/B] [I]Preserving testicular function and reproductive ability remains an ongoing challenge to practitioners prescribing TTh. Exogenous testosterone is known to decrease intratesticular testosterone and thus impair spermatogenesis.[/I] [I]Indeed, in 1996 the World Health organization investigated weekly injections of 200 mg testosterone enanthate (TE) as a form of contraception. The task force demonstrated that TE caused azoospermia in approximately 75% of men after only 6 months of use [71]. Both the American Urological Association and the Endocrine Society published guidelines in 2018 which recommend against TTh in men wishing to preserve fertility [2,72].[/I] [I][U]Current evidence suggests, however, that adjuvant medications can be prescribed in an effort to maintain testicular health and fertility while receiving TTh[/U]. [U]Coadministration of HCG with TTh has been shown to help preserve spermatogenesis in men by maintaining physiologic intratesticular testosterone levels throughout treatment[/U]. In 2005, Coviello et al [58] demonstrated that TTh caused intratesticular testosterone levels to drop by 94% in otherwise healthy, reproductive-aged men. However, adding subcutaneous 250 IU HCG every other day to their TTh regimen prevented this precipitous fall with intratesticular testosterone levels only dropping 7% from baseline. Furthermore, men who received TTh and 500 IU of HCG every other day actually experienced an increase in their intratesticular testosterone by 26% [58]. [U]This study showed that intratesticular testosterone could be reliably maintained while on TTh[/U]. Future studies would prove that spermatogenesis itself, and thus the male’s fertility, could likewise be persevered throughout therapy [U]A retrospective study published by Hsieh et al [73] in 2013 found that out of 26 men treated with TRT and intramuscular 500 IU HCG every other day, no patient became azoospermic[/U]. Nineteen of the 26 patients received injectable testosterone while seven were treated with transdermal testosterone gels. Mean serum hormone levels before vs during treatment were: testosterone 207.2 vs. 1,055.5 ng/dL (p<0.0001), free testosterone 8.1 vs. 20.4 pg/mL (p=0.02). No differences in SA parameters were observed during greater than 1 year of follow-up. During the study’s follow-up, nine men established a pregnancy with their partner [73].[/I] [I][U]This study continues to serve as the foundation of ‘fertility-preserving TTh regimens currently utilized today[/U]. [B]*[U]Sensibly, all men wishing to preserve fertility while on TTh should obtain a baseline SA[/U]. [U]During the initial consultation, it is also important to identify the patient’s goals with regard to the timing of the pregnancy (Table 1)[/U].[/B][/I] [B]Table 1. Summary of recommendations for maintenance of spermatogenesis with TTh or AAS use[/B] [ATTACH type="full" alt="Screenshot (4024).png"]13570[/ATTACH] [B]CONCLUSIONS[/B] [I]Initiating testosterone replacement therapy requires an open and honest discussion between the physician and patient. The risks, benefits, alternatives, and expectations must be reviewed in detail with a specific focus on the reproductive implications involved with treatment. While many side effects of TTh such as cardiovascular impact remain surrounded by controversy, the findings of decreased intratesticular testosterone and subsequent impaired sperm production are well-documented. [U]Fortunately, the aforementioned maneuvers show promise in maintaining testicular health throughout treatment while facilitating the successful restoration of fertility when trying for pregnancy. CC and HCG both play pivotal roles in helping to restore spermatogenesis in these men[/U]. Further randomized, prospective studies are necessary to elucidate the most effective treatment programs both during and after TTh. [U]In the meantime, men considering TTh who are interested in preserving fertility should be treated by experts familiar with the intricacies of these medication regimens[/U].[/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
How loong until sperm production is impacted?
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