Testosterone Therapy for Late-Onset Hypogonadism Improves Erectile Function: A Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Randomized controlled trials (RCTs) of testosterone therapy (TTh) for late-onset hypogonadism are systematically reviewed and a meta-analysis to assess the efficacy of TTh in improving erectile function is performed. <b><i>Methods:</i></b> The PubMed, Cochrane Library, and Web of Science databases were searched to identify RCTs published from 2007. RCTs that assessed erectile function using the erectile function domain of the International Index of Erectile Function (IIEF-EFD) were included in the meta-analysis. <b><i>Results:</i></b> The systematic review included 18 RCTs and the meta-analysis included 6 studies that enrolled a total of 1,458 patients. The overall meta-analysis revealed that the IIEF-EFD score was significantly improved in the TTh group compared with the placebo group (mean difference 1.86; 95% confidence interval 1.01–2.72; <i>p</i> &#x3c; 0.0001). Compared with patients receiving placebo, there was a significant improvement in the IIEF-EFD of patients who received TTh using testosterone gel, those who received TTh for over 30 weeks, and those without diabetes mellitus or metabolic syndrome. <b><i>Conclusion:</i></b> TTh achieved a significant improvement in the IIEF-EFD score of hypogonadal men compared with placebo, especially in those who received testosterone gel, were treated for over 30 weeks, and had no comorbidities.

Testosterone Therapy for Men With Age-Related Low Testosterone: Tempest in a Teacup

Serum testosterone concentrations decrease in men with age, but benefits and risks of raising testosterone levels in older men remain controversial. In the T-Trials, a total of 790 men, age 65 and older, with a serum testosterone concentration of &lt; 275 ng/dL and symptoms of sexual dysfunction, fatigue or physical dysfunction were randomized to either testosterone gel or placebo gel for 1 year. Treatment in the testosterone arm increased serum testosterone levels to the mid-normal range for young men. Testosterone replacement was associated with a significant increase in sexual activity (p&lt;0.001), libido and erectile function. In contrast, there was no improvement in vitality or physical function. Adverse findings included increases in non-calcified plaque formation and a higher rate of prostate events. In sum, testosterone treatment in older men was associated with modest benefits, while the risk on prostate and cardiovascular health remain unclear.

Prevalence of androgen deficiency in aging male in an outpatient population and effects of testosterone gel reposition therapy

Background: Androgen deficiency in aging male (ADAM) is characterized by hypogonadism with symptoms such as reduced sexual desire, muscle mass loss, among others. The treatment with testosterone gel and the results around weight and other indicators are the research objects. Objective: Analysis of association between ADAM and obesity in the outpatient population studied and to verify the outcomes of the testosterone gel treatment. Materials & Methods: From a group of 126 outpatients of University Hospital Mário Palmério, 40 were selected with total testosterone lower than 300ng/dL, upon the signature of written informed consent form and the realization of laboratory tests. After new testosterone dosage and urologic evaluation, 6 patients were treated for an average time of 6 months. Initially the dosage was 50 mg/day, with medical consultations and laboratory tests to verify the effects and to adjust the dosage. The variables analyzed were BMI, abdominal circumference, weight, muscle mass, body and visceral fat, in addition to testosterone serum dosages, lipid profile, amongst others, considering the test t among the beginning and end of treatment, defining the significance level by p<0,05. Results: Significant increase of total testosterone levels (p<0,001) and a tendency of improvement in the free testosterone levels (p=0,061) and no significant reduction of BMI (p=0,4308), abdominal circumference (p=0,1695), weight (p=0,999), body fat (p=0,194) and muscle mass (p=0,632), while visceral fat increased (p=0,5265). Vitamin D had no significant increase (p=0,2422). Conclusion: The total testosterone level was increased after the testosterone gel treatment with statistical significance, however there must be new research with more subjects with ADAM to prove the benefits of this treatment.

Role of transdermal testosterone gel pre-treatment on IVF outcome: a prospective randomized controlled trial with active control

Background: Dealing with poor ovarian responders is the newest challenge for the present-day reproductive physicians. Androgens are said to increase pregnancy outcomes due to enhanced oocyte retrieval in poor responders. The aim of the study was to measure the effect of transdermal testosterone gel in women with unexplained poor ovarian response.Methods: It was a prospective randomized controlled trial with active control conducted at ART centre, department of obstetrics and gynaecology, AIIMS, New Delhi from August 2017-August 2018. Seventy women with previously failed IVF/ICSI who had ≤5 oocyte retrieval in previous cycle having normal ovarian reserve with normal or low testosterone levels were randomized. Study arm (N=35) received testosterone gel pre-treatment whereas the control arm (N=35) received standard treatment. GnRH antagonist stimulation protocol was followed. The number of oocytes retrieved and pregnancy outcomes were studied.Results: Of the 70 women in the study, the number of oocytes retrieved was significantly higher (6.5±5.8 vs 3.1±2.1; p=0.002), cycle cancellation rate was lower (8.6% vs 22.9%; p=0.094), implantation rate (8.2% vs 2.6%; p=0.228), clinical pregnancy, ongoing pregnancy, live birth rates (14.7% vs 2.9%; p=0.092) and take home baby rates (17.6% vs 2.9%; p=0.049) were higher in testosterone group compared to controls. One woman in testosterone group developed mild OHSS.Conclusions: The study shows that transdermal testosterone gel is found to improve oocyte retrieval significantly in unexpected poor responders, although there was not a significant improvement in pregnancy outcomes. Hence further studies are of utmost importance to establish the effectiveness of the gel.

P–612 Transdermal testosterone vs. Placebo (lubricant gel) pre-treatment in improving IVF outcomes in diminished ovarian reserve patients (POSEIDON group 3 and 4): a randomised controlled trial

Study question To compare the efficacy of transdermal testosterone with placebo (lubricant gel) in improving IVF outcomes using GnRH antagonist protocol in POSEIDON group 3 and 4 patients. Summary answer Patients receiving pre-treatment with testosterone gel had higher mean number of oocytes retrieved and grade A embryos as compared to the patients receiving lubricant gel. What is known already Diminished ovarian reserve (DOR) is associated with suboptimal ovarian response, higher cycle cancellation rate and lower clinical pregnancy rate following IVF cycles. Various treatment regimens have been devised for management of such patients and use of adjuvants in the form of oral or transdermal androgen is one of them. Androgens improves follicular response to gonadotropin stimulation as well as increase FSH receptor expression in granulosa cells, in turn leading to better oocyte yield and pregnancy rate. Aim was to compare the effect of transdermal testosterone gel with placebo gel on ART outcome in DOR patients (POSEIDON Group 3 and 4). Study design, size, duration A prospective, randomised controlled trial was carried out from 1st September 2019 to 31st October 2020 at a tertiary infertility centre in India. 50 patients fulfilling the criteria of Group 3 and Group 4 of POSEIDON classification were included in the study. Patients with endocrine disorders (thyroid, prolactin), endometrioma, history of surgery on the ovaries, sensitivity to testosterone gel, male factor infertility and deranged liver and renal function tests were excluded. Participants/materials, setting, methods Enrolled patients were randomised into two groups of 25 patients each, one group was pretreated (TTG group) with transdermal testosterone gel, 12.5 mg/day from day 6th of previous cycle to day 2nd of stimulation cycle while patients in other group took lubricant gel for the same duration before stimulation with GnRH antagonist fixed protocol followed by fresh Day 3 transfer. Main results and the role of chance The baseline characteristics of the two groups were comparable. The primary outcome measures were the number of oocytes retrieved and number of grade A embryos formed (according to Istanbul consensus). The secondary outcome measures were implantation rate, clinical pregnancy rate, miscarriage rate and ongoing pregnancy rate. The mean number of oocytes retrieved in TTG group was 5±1.02 which was significantly higher than placebo group–3.5±1.2, (p &lt; 0.001). The mean number of Grade A embryos were also significantly higher (4.78±0.54 vs 3.00±0.23, p &lt; 0.001) in TTG group. The TTG group had higher implantation rate (28% vs 20%, p = 0.49), clinical pregnancy rate (32% vs 18%, p = 0.41), ongoing pregnancy rate (32% vs 16%, p = 0.38) and lower miscarriage rate (0% vs 20%, p = 0.38), however, these differences were not statistically significant. Limitations, reasons for caution The study was done at a single centre with small sample size, replication with more subjects and in different centers is needed. Wider implications of the findings: Pre-treatment with testosterone gel in DOR patients improves ovarian response to stimulation and results in higher number of oocytes retrieved and good quality embryos resulting in improved clinical pregnancy rates. Transdermal testosterone is advantageous because of better bioavailability, easy application, patient friendly and less adverse effects. Trial registration number MCDH/2019/54