scholarly journals Recovery of Male Reproductive Endocrine Function Following Prolonged Injectable Testosterone Undecanoate Treatment

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A726-A727
Author(s):  
Nandini Shankara-Narayana ◽  
Reena Desai ◽  
Ann Conway ◽  
Bronwyn Gwenneth Ann Stuckey ◽  
Warrick John Inder ◽  
...  

Abstract Background: Exogenous androgen treatment suppresses the hypothalamo-pituitary testicular (HPT) axis causing reduced serum LH, FSH and testosterone (T). Recovery of male reproductive endocrine function in past androgen abusers takes 9-18 months with persistent mild lowering of serum T. The natural history of recovery of HPT axis following prolonged injectable testosterone undecanoate (TU) treatment at standard dose is not known. Therefore, the Runoff Study investigated the rate and extent of reproductive hormone recovery over 12 months following cessation of 2 years of TU treatment in the Testosterone for Diabetes Mellitus (T4DM) Study, while men remain blinded to treatment allocation. Methods: T4DM participants without pathological hypogonadism (n=1007) were randomised to TU or Placebo (P) injections every 3 months for 2 years with 303 subsequently volunteering to enter the Runoff study at 12 weeks after last injection. Before T4DM study unblinding, they provided blood samples and validated sexual function questionnaires (PDQ, IIEF-15) at entry (3 months after last injection), 6, 12, 18, 24, 40 and 52 weeks later. Serum steroid profile (T, DHT, E2, E1) was measured batchwise by LCMS and serum LH, FSH and SHBG by immunoassays. Results: Runoff study participants in both groups were similar and did not differ from all T4DM participants. As expected, at entry to Runoff serum T was higher in TU-treated men but at all timepoints from 12 weeks onwards serum T and SHBG remained consistently 11% and 13%, respectively, lower in TU-treated than in P-treated men. Similarly, at entry sexual function scores were higher in TU-treated men but subsequently no different from P-treated men. Serum LH and FSH recovered slowly with the median time to reach their own pre-treatment baseline of serum LH was 51.1 weeks [95% CI 50.4 – 53.0 weeks] and for serum FSH was 52.7 weeks [51.0 – 60.9 weeks]. Conclusion: After stopping 2 years of standard dose injectable TU treatment in men without pathological hypogonadism, recovery of testicular endocrine function is eventually complete but slow with serum gonadotropin recovery taking on 12 months since the last dose. Persistent mild, proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than signifying androgen deficiency. This suggests that recovery from androgen-induced HPT axis suppression depends primarily on time since cessation rather than dose or duration of androgen exposure.

2022 ◽  
Author(s):  
David J Handelsman ◽  
Reena Desai ◽  
Ann J Conway ◽  
Nandini Shankara-Narayana ◽  
Bronwyn Ga Stuckey ◽  
...  

Context: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective: To investigate rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Methods: Men (n=303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo(P)-controlled randomized clinical trial of TU treatment were recruited for a further 12 months while remaining blinded to treatment. Sex steroids (T, DHT, E2, E1) by LCMS, LH, FSH and SHBG by immunoassays and sexual function questionnaires (Psychosexual Diary Questionnaire (PDQ), International Index of Erectile Function (IIEF), SF-12) were measured at entry (three months after last injection) and 6, 12, 18, 24, 40 and 52 weeks later. Results: In the nested cohort of TU-treated men, serum T was initially higher but declined to 12 weeks remaining stable thereafter with serum T and SHBG 11% and 13%, respectively, lower than P-treated men. Similarly, both questionnaires showed initial carryover higher scores in T-treated men, but after weeks 18 showed no difference between T and P treated men. Initially fully suppressed serum LH and FSH recovered slowly towards the participant’s own pre-treatment baseline over 12 months since last injection. Conclusions: After stopping 2 years of 1000 mg injectable TU treatment, full reproductive hormone recovery is slow and progressive over 15 months since last testosterone injection but may take longer than 12 months to be complete. Persistent proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than androgen deficiency.


2009 ◽  
Vol 16 (2) ◽  
pp. 281-287 ◽  
Author(s):  
Sigrid Svalheim ◽  
Erik Taubøll ◽  
Gerhard Luef ◽  
Andreas Lossius ◽  
Markus Rauchenzauner ◽  
...  

1986 ◽  
Vol 111 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Y. Chandrasekhar ◽  
M. J. D'Occhio ◽  
B. P. Setchell

ABSTRACT This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males. J. Endocr. (1986) 111, 245–253


2021 ◽  
Vol 10 ◽  
Author(s):  
Mir Sadat-Ali ◽  
Khalid W. AlTabash ◽  
Haifa A. Al-Turki ◽  
Sulaiman A. AlMousa ◽  
Hasan N. AlSayed

Abstract The recommended daily dose of vitamin D is 2000 IU was found to be insufficient in many patients. The objective of the present study is to find whether the daily dose of vitamin D should be based on BMI. Two hundred and thirty patients with an established vitamin D deficiency (serum level of 25 Hydroxy vitamin D3 (25OHD3) of ≤20 ng/ml) and patients with BMI ≥30 kg/m2 were included in the study. Demographic data, comorbidities and BMI were recorded. Pre-treatment and post-treatment serum 25OHD3, calcium, phosphorus and parathyroid hormone (PTH) were tested at 0-, 3- and 6-month periods. Patients were treated with a standard dose of 50 000 IU of vitamin D weekly and 600/1200 mg of calcium a day. Once their level of 25OHD3 reached ≥30 ng/ml, patients were randomised into two groups. Group A received a standard recommended maintenance dose of 2000 IU daily and Group B patients received 125 IU/kg/m2 of vitamin D3. The data were entered in the database and analysed. The mean age of Group A was 50⋅74 ± 7⋅64 years compared to 52⋅32 ± 7⋅21 years in Group B. In both groups, pre-treatment vitamin D level was ≤15 ng/ml and increased to 34⋅6 ± 2⋅6 and 33⋅7 ± 2⋅4 ng/ml at the end of 3 months treatment with a dose 50 000 IU of vitamin D3 and calcium 600/1200 mg once a day for group A and group B, respectively. At 6 months, patients in Group A 25OHD3 level was 22⋅8 ± 3⋅80 and in Group B was 34⋅0 ± 1⋅85 ng/ml (P < 0⋅001). This preliminary study suggests that obese patients need higher dosage of vitamin D than the recommended dose. It is prudent that the dosage should be based on the BMI to maintain normal levels for a healthy musculoskeletal system.


PEDIATRICS ◽  
1983 ◽  
Vol 72 (3) ◽  
pp. 384-389
Author(s):  
Harold K. Marder ◽  
Laxmi S. Srivastava ◽  
Stephen Burstein

Serum gonadotropin and testosterone concentrations were measured in ten peripubertal boys to assess the effects of uremia on pubertal maturation. Serum luteinizing hormone (LH) concentrations were elevated for stage of puberty in eight boys, whereas in most boys serum follicle-stimulating hormone and testosterone concentrations were normal. Serum LH concentrations correlated with the severity of uremia. LH levels declined when measured 1 year after the initial measurements in four boys who received renal allografts, but were further elevated in two boys who were treated conservatively. Elevated serum LH concentrations in the presence of normal serum testosterone concentrations imply limited testicular sensitivity to the effects of LH in these peripubertal boys, as has been documented for adult men with chronic renal failure. Alternatively, there may be accumulation of an immunoreactive LH molecule that lacks bioactivity. A testicular dysfunction may explain the pubertal delay experienced by some uremic adolescent boys.


2019 ◽  
Vol 6 (1) ◽  
pp. e000315 ◽  
Author(s):  
Sarah Keegan ◽  
Jeremy H Rose ◽  
Zohra Khan ◽  
Francois-Xavier Liebel

BackgroundCytosine arabinoside (CA) and prednisolone are drugs commonly used together in the management of canine non-infectious meningoencephalitis (NIME). The aim of this study was to report the haematological findings before and after CA and prednisolone treatment and identify any adverse haematological events in this clinical setting, following the veterinary cooperative oncology group established common terminology criteria for recording adverse events following administration of chemotherapy or biological antineoplastic therapy.ResultsWhile 48 patients with a presumptive diagnosis of NIME had pretreatment haematology results, only 12 patients met the inclusion criteria of also having post-treatment haematology results available for review after being treated with prednisolone and CA at a standard dose (200 mg/m2) in a single referral hospital in the UK. Forty-nine post-treatment haematology results were available for these 12 patients.ConclusionsFour adverse haematological events were identified in four patients. None of these events were convincingly attributable to CA administration.


2008 ◽  
Vol 20 (9) ◽  
pp. 55
Author(s):  
S. H. Liew ◽  
A. E. Drummond ◽  
J. E. Margaret ◽  
J. K. Findlay

Gonadotrophins and steroid hormones are vital in controlling the cyclical pattern of ovarian follicular development essential for fertility. Previous studies have shown that ArKO (aromatase knockout) female mice are infertile due to the absence of oestrogen, elevated levels of circulating gonadotrophins and testosterone and folliculogenic disruption. Therefore, the aim of this study was to determine the effects of E2 (oestradiol-17β) replacement, Acyline (GnRH antagonist) and Flutamide (anti-androgen) treatment on ArKO female mice. WT and ArKO female mice (C57B6/J129; 16 weeks old; n = 6–8/grp) were assigned into three main groups: group 1 - received either E2 (0.05 mg) pellet or placebo, group 2 - received either a single s.c. injection of acyline (1.5 mg/kg/week) or placebo and group 3 – received either flutamide (25 mg) pellet or placebo for 3 weeks. Mice were subjected to daily vaginal smears. The ovaries and uterine horns were collected and weighed. One ovary and the uterine horns were fixed in formalin for histological assessment, while the other ovary was snap frozen in Ultraspec solution for RNA isolation and gene expression studies. Serum was collected for hormone measurements. All female ArKO mice exhibited an abnormal cycle that alternated between diestrus and early oestrus. E2 replacement restored the oestrus cycle in ArKO female mice but acyline and flutamide treatment did not. Histologically, hemorrhagic cystic follicles were present in all placebo, acyline and flutamide treated ArKO ovaries, however, E2 replacement improved the ovarian and uterine phenotypes. E2 replacement and acyline treatment also led to a decrease in serum gonadotropin levels in ArKO mice. In summary, E2 replacement could reverse the abnormal reproductive phenotype of the ArKO female mice. This study suggests that the reproductive phenotype of the ArKO female mouse is due to the direct effect of oestrogen and not due to the elevated circulating levels of gonadotrophins and testosterone. Supported by NH&MRC (Regkeys 241000, 338510 and 198705)


2016 ◽  
Vol 44 (4) ◽  
pp. 143 ◽  
Author(s):  
Jose RL Batubara ◽  
Arwin Akib ◽  
Diah Pramita

Background Delayed puberty is the most common endocrine com-plication in thalassemia major. The main cause of delayed pu-berty in thalassemia major is the failure of the hypothalamic-pitu-itary axis due to iron accumulation in the pituitary.Objectives The purpose of this study was to determine the preva-lence of delayed puberty in β-thalassemia major patients in theDepartment of Child Health, Cipto Mangunkusumo Hospital,Jakarta. This study also evaluated the adequacy of chelationtherapy and determined serum gonadotropin and sex hormonelevels in these patients.Methods Seventy-two patients with β-thalassemia major aged 13-18 years old who visited the Thalassemia Outpatient Clinic of CiptoMangunkusumo Hospital during February-July 2003 were includedin the study. Each subject underwent examinations to determinethe body weight and height, pubertal status, serum iron level, totaliron binding capacity, and the levels of serum LH, FSH, estradiol(in girls) or testosterone (in boys).Results Delayed puberty occurred in 40 of 72 patients (56%). Themajority of patients with delayed puberty showed low levels of se-rum LH, estradiol, and testosterone whereas low levels of serumFSH only occurred in 6 of 21 boys and 11 of 19 girls. Most of thepatients without delayed puberty had normal levels of serum LH,FSH, and estradiol, but 8 of 16 boys showed decreased serumtestosterone levels. Only 3 patients used chelation therapy ad-equately, all of them showed normal puberty.Conclusions The prevalence of delayed puberty in β-thalassemiamajor patients in this study was still high (56%). Periodic examina-tion and recording of pubertal stage need to be done in girls whohave reached 8 years old and boys who have reached 9 years oldso that early detection and management of delayed puberty canbe done.


2019 ◽  
Vol 31 (04) ◽  
pp. 230-234
Author(s):  
Ole Köhler-Forsberg ◽  
Louisa G. Sylvia ◽  
Charles L. Bowden ◽  
Joseph R. Calabrese ◽  
Michael E. Thase ◽  
...  

AbstractBackground:Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.Methods:Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.Results:Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC &lt; 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.Conclusions:An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.


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