Testosterone Gel Research Articles

Experience in the treatment of patients with androgenic deficiency and comorbidity pathology

Background. Age-related involution of the male reproductive system, known as testosterone deficiency syndrome, andropause, androgen deficiency in the aging male, or partial androgen deficiency in the aging male, causes clinical manifestations that impair quality of life and increase the risk of mortality, especially from cardiovascular disease. In Russia, the problem of hypodiagnosis of androgen deficiency remains up-to-date, with a low frequency of prescription of replacement therapy. Aim. At assessing the effectiveness of testosterone in the rehabilitation of patients with hypogonadism and cardiovascular pathology. Materials and methods. It involved 36 men aged 25–75 years with various cardiological pathologies. Results. As a result of the study, testosterone as a form of a transdermal gel is effective at doses of 50 mg/day. Three-month use of testosterone gel increases the level of testosterone to 2.9 nmol/l (p0.05). Conclusion. Thus, testosterone may play a key role in the treatment of hypogonadism and related cardiovascular diseases, although its safety and feasibility remain a matter of debate.

Single-arm study of testosterone gel replacement therapy and ambulatory blood pressure outcomes in men with hypogonadism.

Studies examining ambulatory blood pressure (BP) response to testosterone replacement therapy are needed owing to inconsistent prior findings across formulations. This study assessed testosterone gel 1.62% and 24-h ambulatory BP. Single-arm non-inferiority trial (NCT04274894) conducted at 36 US sites enrolled 246 men with hypogonadism (mean age, 57.6 years; mean office systolic/diastolic BP [SBP/DBP], 129.8/79.5mm Hg) who were treated for 16weeks with once-daily testosterone gel treatment (starting dose, 40.5mg/day; min, max dose, 20.25, 81.0mg/day) to achieve testosterone concentration of 350-750ng/dL. Main outcome measures included mean change in 24-h average SBP (primary endpoint) and DBP from baseline to week 16. The non-inferiority threshold was a two-sided 95% confidence interval (CI) upper limit <3.0mm Hg for 24-h average SBP. Increase in mean±SD serum testosterone concentration to a physiologic level (baseline, 244.4±93.9ng/dL; week 16, 502.5±394.4ng/dL) was associated with a 1.9-mm Hg mean change in 24-h average SBP observed in the primary analysis (baseline, 123.5mm Hg; week 16, 125.4mm Hg; 95% CI, 0.63-3.13mm Hg; n=169). As the upper CI limit modestly exceeded the non-inferiority margin (3mm Hg), study drug effect on SBP could not be ruled out. Non-inferiority was observed in subgroups without hypertension or diabetes (95% CI, upper limit <3.0mm Hg) and was not observed in those with hypertension or diabetes. Daytime SBP and DBP changes were larger compared with nighttime. No clear cardiovascular adverse events or new safety signals were identified. While the effect of testosterone gel 1.62% on 24-h average SBP could not be ruled out based on the study's non-inferiority margin, the clinical relevance of the small-magnitude mean increase of 1.9mm Hg is anticipated to be minimal considering the results of the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events. ClinicalTrials.gov identifier: NCT04274894 (registered February 17, 2020).

Effect of transdermal testosterone therapy on mood and cognitive symptoms in peri- and postmenopausal women: a pilot study.

The purpose of this study was to assess the impact of testosterone therapy on mood and cognitive symptoms in perimenopausal and postmenopausal women. A retrospective cohort study undertaken in a UK specialist menopause clinic. 510 women using hormone replacement therapy (HRT) with persistent low libido, cognitive and negative mood symptoms were treated with testosterone cream or gel for 4 months. A modified version of the Greene Climacteric Scale was used to measure self-reported symptom frequency and severity at baseline and 4 months after initiating treatment. All nine cognitive and mood symptoms significantly improved across the study period. Mood improved more than cognition (47% of women reported an improvement in mood vs. 39% reported an improvement in cognition; 34% vs. 22% decrease in mean symptom scores, respectively). Regarding libido, 52% of women reported an improvement; mean symptom score decreased by 33%. Transdermal testosterone therapy for 4 months was associated with significant improvements in mood and cognition. Further research including randomised clinical trials are needed to establish the long-term efficacy and safety of testosterone for the treatment of menopausal cognitive and psychological symptoms.

Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225mg oral testosterone undecanoate twice daily, and doses were adjusted by 75mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. Overall mean±SD baseline testosterone was 205.7±71.6ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91vs. -0.10; p=0.035), and mental component summary (3.82vs. 0.55; p=0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57vs. -0.20; p=0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. Male patients with hypogonadism receiving oral testosterone undecanoate 225mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

EP360 - Pitfalls in the management of transgender patients: a case report and discussion

Abstract Introduction There has been an increase in the number of transgender individuals in the population. In a clinical setting, this introduces potential patient safety issues from misidentification of biological sex, particularly in emergency scenarios. We report one such patient. Case report A 21-year-old ‘male’ patient presented with right iliac fossa pain. No surgical history was reported by the patient or GP records. Repeat medication included Testosterone gel. Bloods showed raised amylase though the clinical picture suggested appendicitis so a CT scan was done. This was reported normal but also identified normal sized uterus/ovaries! Following a sensitive discussion with the patient, ‘they’ revealed that ‘they’ were born biologically female and were on gender-affirming hormone-therapy. The patient was successfully managed conservatively. Discussion Our case report highlights the potential risks of misidentification of biological sex in an acute-abdomen scenario. Misdiagnosis is most critical - all gynaecological causes of abdominal pain (e.g. PID/ life- threatening ectopic-pregnancy) were missed. Due to the risk of ionizing radiation to unborn children, CT require the pregnancy status of patients with childbearing capacity, prior to the scan: this therefore should include transgender ‘males’ who have not undergone sex-reassignment surgery. There are also patient safety/ comfort issues with admission in single- sex wards. Conclusion It is important to identify transgender patients in order to avoid misdiagnosis and hence mismanagement. Taking detailed history including medication will help with this, as some transgender individuals may not volunteer details regarding their biological sex. Sensitive communication is vital to avoid any feeling of discrimination/stigmatisation.

Testosterone rapidly increases men’s emotion-based dehumanization of a conservatively dressed woman

Past research has found that sexualized women are often dehumanized (i.e., attributed reduced human qualities). However, the mechanisms contributing to such dehumanization remain poorly understood. In this pre-registered experiment involving a within-subject, placebo-controlled, cross-over design, we tested whether testosterone contributes to men’s (N = 120, age range: 18–38 years) dehumanization of women. After administration of intranasal testosterone or placebo gel, men watched a video of a woman wearing either modest (i.e., conservative) or revealing (i.e., sexualized) clothing (between-subjects factor) and then completed three subtle dehumanization tasks, measuring emotion-based, personality-based, and perceptual dehumanization. We hypothesized that testosterone would increase dehumanization, especially for men who watched the “sexualized-clothing” video. Instead, we found that, while men engaged in emotion-based dehumanization toward the sexualized woman both when they had testosterone and placebo, testosterone increased emotion-based dehumanization toward the conservatively dressed woman. Other forms of dehumanization were not affected by testosterone. We also explored whether personality (e.g., dominance) and biological (e.g., CAG repeat polymorphism) traits that have been found to moderate the effects of testosterone on some social behaviors also moderated the effects examined here, but we did not find any significant moderations. Overall, this experiment revealed a novel physiological mechanism affecting emotion-based dehumanization.

Off-label use of clomiphene citrate to treat anabolic androgenic steroid induced hypogonadism upon cessation among men (CloTASH) – A pilot study protocol

BackgroundNon-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. MethodsIn this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.

Low reproducibility of plasma testosterone concentrations in male patients with hypogonadism treated with transdermal testosterone gel

Low reproducibility of plasma testosterone concentrations in male patients with hypogonadism treated with transdermal testosterone gel

Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism

The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown. To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes. This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022. Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion. The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes. Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes. In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism. ClinicalTrials.gov Identifier: NCT03518034.

(334) Worldwide Interest in Testosterone Replacement Therapy

Abstract Introduction Testosterone therapy has gained popularity in recent decades, with various methods of administration available, such as oral, topical, injection, and implantable routes. As a wider variety of treatment options arise, knowledge regarding the public interest in varying modalities may give providers an insight to patient preferences and assist in the counseling of patients seeking to initiate testosterone replacement therapy. Objective To examine public interest in the different methods of testosterone administration across the United States and compare their relative popularity to intramuscular injections. Methods Utilizing Google Trends, data pertaining to searches related to diverse testosterone administration methods were collected over a ten-year duration. The categories under analysis encompassed 1) testosterone injections, 2) implanted testosterone, 3) oral testosterone, and 4) topical testosterone. Controlled search terms, including news and weather queries, were employed. Search term trends were quantified in arbitrary units (a.u.) and plotted against the corresponding time period. Results Testosterone injection had the highest average search intent from Google Trends during the past 10 years (63.08 +/- 12.7 a.u.), followed by testosterone pills (60.56 +/- 13.4 a.u.), testosterone pellets (53.14 +/- 19.4 a.u.), testosterone patches (51.03 +/- 16.2 a.u.), and lastly testosterone gel (17.29 +/- 21.5 a.u.) A notable upward trend was recorded for all searches, with the highest increase in searches seen for implanted testosterone (m = 0.433), testosterone injections (m = 0.297), oral testosterone (m = 0.222), and lastly topical testosterone (m = 0.050) (Figure 1). Conclusions This study provides compelling evidence that all modes of testosterone administration had increasing search trends, most notably implantable testosterone therapies followed by testosterone injections, and oral testosterone, which may be in line with recent FDA approvals since 2019 for newer oral (Jatenzo, Tlando, Kyzatrex) and implantable (ex: Xyosted) options. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma, Clarus Therapeutics, Coloplast.

Testosterone Treatment and Fractures in Men with Hypogonadism

BackgroundTestosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed.MethodsIn a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.4 nmol per liter), in fasting plasma samples obtained at least 48 hours apart. Participants were randomly assigned to apply a testosterone or placebo gel daily. At every visit, participants were asked if they had had a fracture since the previous visit. If they had, medical records were obtained and adjudicated.ResultsThe full-analysis population included 5204 participants (2601 in the testosterone group and 2603 in the placebo group). After a median follow-up of 3.19 years, a clinical fracture had occurred in 91 participants (3.50%) in the testosterone group and 64 participants (2.46%) in the placebo group (hazard ratio, 1.43; 95% confidence interval, 1.04 to 1.97). The fracture incidence also appeared to be higher in the testosterone group for all other fracture end points.ConclusionsAmong middle-aged and older men with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo. The fracture incidence was numerically higher among men who received testosterone than among those who received placebo. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.)

Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy.

The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood. We assessed the effects of testosterone-replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial. A randomized, placebo-controlled, double-blind study was conducted at 316 trial sites. Participants included men, aged 45 to 80 years, with 2 fasting testosterone levels less than 300 ng/dL, 1 or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated 3 subgroups of participants: (1) men with rigorously defined, late-life-onset, low-grade persistent depressive disorder (LG-PDD, previously "dysthymia"); (2) all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and (3) all randomly assigned men. Intervention included 1.62% transdermal testosterone or placebo gel. Outcome measures included the proportions of participants (1) meeting criteria for LG-PDD or (2) with significant depressive symptoms; and changes in depressive symptoms, energy, sleep quality, and cognition in testosterone-treated vs placebo-treated men in the 3 subgroups. Of 5204 randomly assigned participants, 2643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met rigorous criteria for LG-PDD. Among those with LG-PDD, there was no significant difference in any outcome measure between the TRT and placebo groups, possibly reflecting low statistical power. In men with significant depressive symptoms (n = 2643) and in all randomly assigned participants (n = 5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. Depressive symptoms are common in middle-aged and older men with hypogonadism but LG-PDD is uncommon. TRT is associated with small improvements in mood and energy in hypogonadal men with and without significant depressive symptoms.

Long Term Cardiovascular Safety of Testosterone Therapy: A Review of the TRAVERSE Study.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism. Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-to-event analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

Development of an In Vitro secondary transfer model for testosterone gel to elucidate protocols of safe contact.

Testosterone gels applied to skin carry a risk of secondary transfer to non-patients , leading to development of symptoms such as precocious purberty. Currently, there is a lack of&amp;nbsp;in vitro&amp;nbsp;data available to inform guidance over safe contact parameters. A secondary transfer model using porcine skin to model primary (patient) skin and secondary (contact) skin was employed, with testosterone permeation and distribution analysis after 24 hours. Primary skin saw increasing amounts of unabsorbed testosterone and a reduction in delivery to the skin during at later contact times. Secondary skin saw a reduction in unabsorbed testosterone and delivery with later contact times. Permeation data mirrored the distribution data. These differences could be explained by changes in the formulation on the skin surface after application.

Testosterone administration decreases sensitivity to angry facial expressions in healthy males: A computational modeling approach

Previous research indicates that higher testosterone levels are related to increased aggressive and dominant behaviors, particularly in males. One possible mechanism for these hormone-behavior associations could involve threat perception. However, the causal influence of testosterone on men's recognition of threatening facial expressions remains unknown. Here, we tested the causal effect of exogenous testosterone on men's sensitivity to facial threat by combining a psychophysical task with computational modeling. We administered a single dose (150 mg) of testosterone or placebo gel to healthy young men (n = 120) in a double-blind, placebo-controlled, between-participant design. Participants were presented with morphed emotional faces mixing anger/fear and neutral expressions and made judgments about the emotional expression. Across typical regression analysis, signal detection analysis, and drift diffusion modeling, our results consistently showed that individuals who received testosterone (versus placebo) exhibited a lower perceived sensitivity to angry facial expressions. But we observed no significant effects of testosterone administration on fearful facial expressions. The findings indicate that testosterone attenuates sensitivity to facial threat, especially angry facial expressions, which could lead to a misestimation of others' dominance and an increase in one’s own aggressive and dominant behaviors.

Management of Poor Ovarian Response

Poor ovarian response (POR) occurs in approximately 9-24% of patients in ART. It presents a challenge to the reproductive consultant and causes immense emotional distress to the couple. Over the last few decades, ART has seen an improvement on both the clinical and embryological front however, adequate management of POR remains elusive. Etio-pathogenesis of the condition is poorly understood and varying definitions of POR have been used in studies. In recent years the POSEIDON criteria have been proposed to define this group of ‘low-prognosis’ patients and to optimize management. POSEIDON groups are assigned based on age and ovarian reserve. The patient groups are thus the unexpected poor responder’s having a normal ovarian reserve and the expected poor responders who have a poor ovarian reserve, to begin with. Management strategies to improve oocyte numbers and quality include manipulation of pituitary suppression and OS regimes, addition of LH and use of mild stimulation. The Duo- stim protocol has proved successful in increasing egg numbers, using the follicular and luteal phases of the same cycle. Adjuvant therapies which have shown promise in recent years are the use of Testosterone gel, Growth hormone, Co-enzyme Q10. Ovarian rejuvenation using Intra-ovarian platelet-rich plasma, ovarian activation and use of autologous stem cells is exciting and ongoing research in this area may yield evidence in future. The speaker will share her experience with the use of IOPRP for improving ovarian reserve during the lecture.

Hepcidin Reduction during Testosterone Therapy in Men with Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Study.

A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n = 20) or placebo gel (n = 19) for 24 weeks. We included 39 men (50-70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed with DXA- and MRI-scans; the main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Hepcidin levels decreased during TRT (β = -9.5 ng/mL, p < 0.001), lean body mass (β = 1.9 kg, p = 0.001) increased, and total fat mass (β = -1.3 kg, p = 0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Falsely elevated serum testosterone measurements resulting from testosterone topical gel contamination of the venipuncture site: Case Series and retrospective review

Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. In monitoring testosterone serum concentrations, contamination of the phlebotomy site by testosterone topical gel can lead to supraphysiologic (>1000 ng/dL or 34.7 nmol/L) serum concentrations of testosterone, as demonstrated in a few published case reports. The frequency of this issue is currently not known. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. Documentation in the electronic health record revealed 7 patients where contamination of the phlebotomy site by topical gel was strongly supported as the cause of supraphysiologic testosterone serum concentrations. These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application. Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important.

Investigating the Effect of Transdermal Testosterone Gel Administration on Ovarian Response Rate in Infertile Women with Poor Response to Conventional Assisted Reproductive Methods

Investigating the Effect of Transdermal Testosterone Gel Administration on Ovarian Response Rate in Infertile Women with Poor Response to Conventional Assisted Reproductive Methods

Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism

Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood. To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia. This randomized, placebo-controlled trial included men with hypogonadism at 316 US sites enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. Eligible participants were aged 45 to 80 years, with 2 testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March and August 2023. Participants were randomized with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration. Proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. Secondary end points included incidence of anemia among men who were not anemic. Binary end points were analyzed using repeated-measures log-binomial regression. A total of 5204 men were included, 815 with anemia (mean [SD] age, 64.8 [7.7] years; 247 Black [30.3%], 544 White [66.7%], 24 other [2.9%]) and 4379 without anemia (mean [SD] age, 63.0 [7.9] years; 629 Black [14.4%], 3603 White [82.3%], 147 other [3.4%]). Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs 38 of 97 [39.2%]) (P = .002). Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level. In middle-aged and older men with hypogonadism and anemia, TRT was more efficacious than placebo in correcting anemia. Among men who were not anemic, a smaller proportion of testosterone-treated men developed anemia than placebo-treated men. ClinicalTrials.gov Identifier: NCT03518034.