Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency

Shlykova, Nadezhda; Davidson, Emily; Krakowsky, Yonah; Bolaños, José; Traish, Abdulmaged M.; Morgentaler, Abraham

doi:10.1097/ju.0000000000000630

Cited by 15 publications

(10 citation statements)

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“…However, this is a single institution study with a modest sample size and we based the correlation of 17-OHP with ITT on Amory et al 11 findings and our previous study 12 , since repeatedly performing testicular aspiration was not feasible. Furthermore, both 17-OHP and T are steroid hormones and measurements can vary within samples 31,32 or with the circadian cycle 33 . Additionally, we did not evaluate pregnancy rates or number of live births as an outcome.…”

confidence: 99%

Evaluation of a serum 17-hydroxyprogesterone as predictor of semen parameter(s) improvement in men undergoing medical treatment for infertility

Lima

Rakitina

Blachman‐Braun

2020

CUAJ

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Introduction: The goal of medical therapy for infertile men with testosterone deficiency (TD) is to improve intratesticular testosterone (ITT). There is a gap in knowledge to identify those who will respond with semen parameter(s) improvement. We hypothesized that serum 17-hydroxyprogesterone (17-OHP) — a marker of ITT — can be used to predict improvement of semen parameter(s). Methods: Between July 2018 and January 2020, we conducted a prospective study of 31 men with primary infertility, TD, and secondary hypogonadism receiving clomiphene citrate (CC) and/or human chorionic gonadotropin (hCG) for three months. We assessed baseline and followup hormones, including testosterone, 17-OHP, semen parameter(s), and demographics. Semen quality upgrading was based on assisted reproduction eligibility: in-vitro fertilization (<5 million), intrauterine insemination (IUI) (5–9 million), and natural pregnancy (>9 million). Variables were compared using the Mann-Whitney U or Wilcoxon rank test. Results: Twenty-one men received CC and 10 received CC/hCG. Median followup was 3.7 (3.3–5.1) months. Sixteen men upgraded semen quality. Six of 10 men with baseline total motile sperm count (TMSC) of 0 had motile sperm after treatment, and 11/20 men with TMSC<5 upgraded semen quality into TMSC>5 range. Low 17-OHP was the only factor that predicted semen quality upgrading. Men with 17-OHP ≤55 ng/dL upgraded semen quality and improved hormones, whereas men with 17-OHP >55 ng/dL did not upgrade semen quality. Conclusions: Medical therapy for infertile men with TD resulted in the improvement of sperm concentration, TMSC, testosterone, and 17-OHP. Semen quality upgrading appears to be more significant in patients with low 17-OHP, suggesting that ITT can be used as a biomarker to predict semen parameter(s) improvement.

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confidence: 99%

Evaluation of a serum 17-hydroxyprogesterone as predictor of semen parameter(s) improvement in men undergoing medical treatment for infertility

Lima

Rakitina

Blachman‐Braun

2020

CUAJ

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“…Shlykova et al (page 817) from Brookline, Massachusetts studied whether the same diurnal variation occurred in 21 men 18 to 49 years old (mean age 31.7 years) with and without low T by sampling levels throughout the day. 7 The highest overall T level was observed at 08:00 while the lowest level occurred at 14:00. Men with a low T failed to demonstrate diurnal variation with 24-hour blood sampling leading the authors to speculate that the same central mechanism may be involved in secondary T deficiency as well as loss of circadian rhythm.…”

Section: Absent Diurnal Variation In Serum Testosterone and Testosterone Deficiencymentioning

confidence: 88%

This Month in Adult Urology

Smith¹

2020

Journal of Urology

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“…92 Results from a study by Shlykova et al evaluating endogenous T levels over a 24-h period in 21 healthy male volunteers showed that men with baseline serum T levels <10.4 nmol/L (300 ng/dl) did not demonstrate diurnal variation within the 24-h sampling period. 93 To understand the circadian rhythmicity of T levels in men with TD, a population kinetic model built by Gonzales-Sales et al, using baseline T profiles from 859 men with TD, predicted a base T value of 8.3 nmol/L (239 ng/dl), with the amplitude of oscillation estimated to be 1.1 nmol/L (32.4 ng/dl). 94 Their model also predicted that a stretched cosine function was more suitable to describe the circadian behavior of T levels of men with TD, as trough levels occurred approximately 5 h after peak T levels, and levels then increased until the next peak occurred approximately 19 h later.…”

Section: Oral Testosterone Undecanoate (Tu)mentioning

confidence: 99%

Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age

et al. 2021

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Background: To improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations.Objective: To compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age. Materials and methods:A literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed. Discussion and conclusion:Endogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.

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Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency

Cited by 15 publications

References 0 publications

Evaluation of a serum 17-hydroxyprogesterone as predictor of semen parameter(s) improvement in men undergoing medical treatment for infertility

Evaluation of a serum 17-hydroxyprogesterone as predictor of semen parameter(s) improvement in men undergoing medical treatment for infertility

This Month in Adult Urology

Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age

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