Testosterone Implants Research Articles

Experimentally Elevated Levels of Testosterone Advance Daily Onset of Activity in Short-Day Housed Male House Sparrows (Passer domesticus).

Seasonal changes in sleep/wake cycles and behaviors related to reproduction often co-occur with seasonal fluctuations in sex hormones. Experimental studies have established that fluctuations in circulating testosterone mediate circadian rhythms. However, most studies are performed under constant lighting conditions and fail to investigate the effects of testosterone on the phenotypic output of circadian rhythms, that is, chronotype (daily activity patterns under light:dark cycles). Here, we experimentally elevated testosterone with implants during short nonbreeding daylengths in male house sparrows (Passer domesticus) to test if observed seasonal changes in chronotype are directly in response to photoperiod or to testosterone. We fitted individuals with accelerometers to track activity across treatment periods. Birds experienced three treatments periods: short day photoperiods before manipulation (SD), followed by testosterone implants while still on short days (SD + T). Implants were then removed. After a decrease in cloacal protuberance size, an indicator of low testosterone levels, birds were then photostimulated on long days (LD). Blood samples were collected at night, when testosterone peaks, to compare testosterone levels to daily onset/offset activity for experimental periods. Our results indicate that experimentally elevated testosterone under short nonbreeding photoperiods significantly advanced daily onset of activity and total daily activity relative to daylength. This suggests that testosterone, independent of photoperiod, is responsible for seasonal shifts in chronotypes and daily activity rhythms. These findings suggest that sex steroid hormone actions regulate timing of daily behaviors, likely coordinating expression of reproductive behaviors to appropriate times of the day.

Recent Developments in Promising Hormonal and Non- Hormonal Male Contraceptives: A Review

New male contraceptive methods would expand male and female contraceptive alternatives and enhance male contraceptive agency. Since 1969, a program for developing contraceptives has been financed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which also continues to fund the majority of hormonal male contraceptive development today. Also, the early stages of non-hormonal techniques start to develop. The hormonal male contraceptive methods, include testosterone undecanoate injection plus norethisterone enanthate injection, implants of testosterone plus depo-medroxyprogesterone acetate injection, testosterone enanthate injection, and other testosterone-based methods. The non-hormonal methods, include novel hormone-free substances such as retinoic acid inhibitors, sperm ion channel blockers, and vasal peristalsis blockers. The review provides insights into the efficacy, safety, and potential side effects of each method, and highlights the current state of research and development in the field of male contraception.

Complex effects of testosterone level on ectoparasite load in a ground squirrel: an experimental test for the immunocompetence handicap hypothesis

BackgroundThe immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known.MethodsIn this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual.ResultsWe found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus.ConclusionsOur results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.Graphical

No effect of testosterone or sexual ornamentation on telomere dynamics: A case study and meta-analyses.

Life-history theory predicts that reproductive investments are traded-off against self-maintenance. Telomeres, the protective caps on the ends of chromosomes, offer a promising avenue for assessing life-history trade-offs, as they shorten in response to stressors and are predictive of the remaining lifespan. In males, testosterone frequently mediates life-history trade-offs, in part, through its effects on sexual ornamentation, which is an important aspect of reproductive investment. However, studies of within-individual associations between telomere dynamics and sexual ornamentation are limited in number and have produced mixed results. Furthermore, most such studies have been observational, making it difficult to discern the nature of any causal relationship. To address this, we used short-acting testosterone implants in free-living male superb fairy-wrens (Malurus cyaneus) to stimulate the production of a sexual ornament: early moult into a costly blue breeding plumage. We found no evidence that elevated testosterone, and the consequent earlier moult into breeding plumage, accelerated telomere shortening. We therefore followed up with a systematic review and two meta-analyses (28 studies, 54 effect sizes) exploring the associations between telomeres and (1) testosterone and (2) sexual ornamentation. In line with our experimental findings, neither meta-analysis showed an overall correlation of testosterone or sexual ornamentation with telomere length or telomere dynamics. However, meta-regression showed that experimental, compared to observational, studies reported greater evidence of trade-offs. Our meta-analyses highlight the need for further experimental studies to better understand potential responses of telomere length or telomere dynamics to testosterone or sexual ornamentation.

SAT354 Molecular and Histological Characterization of a Guinea Pig Model of Mild Hyperandrogenemia

Abstract Disclosure: R.N. Tanori: None. J.E. Barboza Sagrero: None. K. Noll-Bader: None. S. Chandu: None. P.E. Chappell: None. C.V. Bishop: Consulting Fee; Self; Oviva, Oxford Pharmaceuticals Inc. There are several rodent models for polycystic ovarian syndrome (PCOS), but unlike primates, most rodents will not form a long-lived corpus luteum (CL) unless they experience cervico-vaginal stimulation/mating. Our research group has begun to determine if guinea pigs (Cavia porcellus), rodents with long-lived CL, are a suitable model for mild hyperandrogenemia, a risk factor for PCOS. The objective of this analysis was to determine the relative abundance of each follicle type within a cross-section of 20-week old guinea pig ovarian tissue from control and T-treated females after 3 months of androgen exposure. Ovarian tissues were collected from six guinea pigs treated with cholesterol implants (vehicle, n=4) or testosterone implants (n=3), which elevated androgen levels ∼2-fold above control females. Tissues were embedded in paraffin wax and cut into serial sections (5 μm) and placed onto glass slides (1 section/slide) for hematoxylin and eosin staining to identify follicle morphology within the ovarian tissue. Every fifth section was stained and analyzed using an ECHO Revolve microscope and follicles counted using ImageJ. Follicles of interest were primordial, primary, multi-layer, antral, and corpus luteum, and counts were normalized to ovarian area. All follicle types were found in all the ovaries imaged, as well as some corpora lutea. Multilayer follicles were significantly reduced by chronic exposure to mild hyperandrogenemia (p=0.01). These should provide needed baseline analyses for future experiments employing guinea pigs as a model of PCOS. In addition to histological analysis, we have begun quantifying gene expression changes for hormones and receptors throughout the reproductive axis. Preliminary studies using qPCR illustrate significantly elevated expression levels of hypothalamic kiss1, pituitary gnrhr, and ovarian fshr in T-treated females. No discernable differences were observed between treatment groups for kiss1r, gnrh, or fshb. Ongoing studies will explore differences in estrogen and androgen receptor expression throughout the reproductive axis, as well as any changes in metabolic regulators in liver and skeletal muscle that are associated with mild hyperandrogenemia in these animals. Presentation Date: Saturday, June 17, 2023

Species differences in hormonally mediated gene expression underlie the evolutionary loss of sexually dimorphic coloration in Sceloporus lizards.

Phenotypic sexual dimorphism often involves the hormonal regulation of sex-biased expression for underlying genes. However, it is generally unknown whether the evolution of hormonally mediated sexual dimorphism occurs through upstream changes in tissue sensitivity to hormone signals, downstream changes in responsiveness of target genes, or both. Here, we use comparative transcriptomics to explore these possibilities in 2 species of Sceloporus lizards exhibiting different patterns of sexual dichromatism. Sexually dimorphic S. undulatus develops blue and black ventral coloration in response to testosterone, while sexually monomorphic S. virgatus does not, despite exhibiting similar sex differences in circulating testosterone levels. We administered testosterone implants to juveniles of each species and used RNAseq to quantify gene expression in ventral skin. Transcriptome-wide responses to testosterone were stronger in S. undulatus than in S. virgatus, suggesting species differences in tissue sensitivity to this hormone signal. Species differences in the expression of genes for androgen metabolism and sex hormone-binding globulin were consistent with this idea, but expression of the androgen receptor gene was higher in S. virgatus, complicating this interpretation. Downstream of androgen signaling, we found clear species differences in hormonal responsiveness of genes related to melanin synthesis, which were upregulated by testosterone in S. undulatus, but not in S. virgatus. Collectively, our results indicate that hormonal regulation of melanin synthesis pathways contributes to the development of sexual dimorphism in S. undulatus, and that changes in the hormonal responsiveness of these genes in S. virgatus contribute to the evolutionary loss of ventral coloration.

Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment

The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. This study aimed to determine the impact of current testosterone and testosterone washout on invitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect invitro fertilization outcomes. C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured invitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. Current long-term testosterone treatment impaired invitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of invitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of invitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.

Post-pubertal testosterone implants in female rats, a model of gender-affirming hormonal therapy, induce hypertension that is exaggerated with aging

Introduction: Early pre-pubertal exposure to androgens induces an increase in blood pressure (BP) and renal injury in females, as seen in polycystic ovary syndrome females. However, it is not clear whether treatment with gender-affirming hormonal therapy (GAHT) in trans-men have an impact on their BP and renal health as adults and with aging. Therefore, the present study was undertaken to test the hypothesis that chronic androgen supplements (starting post-pubertal, model of GAHT) in female-to-male trans-sex rats will increase BP and promote renal injury that are exaggerated with aging. Methods: Female SD rats were implanted with testosterone propionate-filled silastic implants (TP, 7.5 mg/10 mm silastic tube/rat, replaced every 3 wks) starting at 7 wks of age (post-pubertal) until 17 months (mos) of age and compared to controls (CON, empty silastic implants). Serum testosterone was measured by LC/MS at 3 mos of age (n=4/grp). Radiotelemetry transmitters were implanted and mean arterial pressure (MAP) was measured at 3 and 17 mos of age (n=3-6/grp). Body composition was determined at 3 and 17 mos of age (n=3-4/grp). Proteinuria was determined at 3, 5 and 7 mos of age (n=4/grp). Serum and urinary creatinine (Cr) were measured at 7 mos of age and Cr clearance was calculated (n=4/grp). Urinary kidney injury molecule-1 (Kim-1) was measured at 12 mos of age (n=3-4/grp). Results: TP had significantly higher serum testosterone compared to CON (6.4 ± 1.5 vs 0.2 ± 0.05 ng/ml; p&lt;0.05). Despite the similar fat mass, lean mass was significantly higher in TP compared to CON starting at 3 mos of age (253.9 ± 6.7 vs 217.7 ± 5.8 g; p&lt;0.05), until 17 mos of age (325.7 ± 15.1 vs 253.5 ± 3.9 g; p&lt;0.05). Proteinuria was significantly higher in TP compared to CON at 5 and 7 mos of age (7.6 ± 1.1 vs 2.4 ± 0.5 mg/24 h and 10.1 ± 1.6 vs 2.4 ± 0.4 mg/24 h, respectively, p&lt;0.05). Cr clearance was significantly lower (0.24 ± 0.03 vs 0.32 ± 0.02 ml/min/100 g, p&lt;0.05) and urinary Kim-1 was significantly higher (6.3 ± 1.5 vs 3.5 ± 0.2 ng/24 h, p&lt;0.05) in TP compared to CON. Importantly, MAP was significantly higher in TP compared to CON starting at 3 mos of age (112 ± 3 vs 106 ± 4 mmHg, p&lt;0.05), with further increases at 17 mos of age (133 ± 1 vs 117 ± 6 mmHg, p&lt;0.05). Conclusion: Post-pubertal testosterone in female sex promotes renal injury and increases BP, independent of adiposity. Aging promotes further increases in BP, suggesting increased risk of cardiovascular diseases. Future studies should determine the mechanisms behind the increase in BP in the female-to-male trans-sex model. P20GM121334, AHA Career Development Award 938320, P20GM104357, R01HL135089, P01HL051971 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Steroid hormone imbalance drives macrophage infiltration and Spp1/osteopontin+ foam cell differentiation in the prostate.

Benign prostatic hyperplasia (BPH) occurs progressively with aging in men and drives deteriorating symptoms collectively known as lower urinary tract symptoms (LUTS). Age-associated changes in circulating steroid hormones, and prostate inflammation have been postulated in the etiology of BPH/LUTS. The link between hormones and inflammation in the development of BPH/LUTS is conflicting because they may occur independently or as sequential steps in disease pathogenesis. This study aimed to decipher the prostatic immune landscape in a mouse model of lower urinary tract dysfunction (LUTD). Steroid hormone imbalance was generated by the surgical implantation of testosterone (T) and estradiol (E2) pellets into male C57BL/6J mice and gene expression analysis was performed on ventral prostates (VPs). These experiments identified an increase in the expression of macrophage markers and Spp1/osteopontin (OPN). Localization studies of OPN pinpointed that OPN+ macrophages travel to the prostate lumen and transition into lipid-accumulating foam cells. We also observed a significant increase in the number of tissue macrophages in the VP which was prevented in OPN-knockout (OPN-KO) mice. In contrast, mast cells, but not macrophages, were significantly elevated in the dorsal prostate of T + E2-treated mice which was diminished in OPN-KO mice. Steroid hormone implantation progressively increased urinary frequency, which was ameliorated in OPN-KO mice. Our study underscores the role of age-associated steroid hormone imbalances as a mechanism of expanding the prostatic macrophage population, their luminal translocation, and foam cell differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Honorary Lifetime Membership Award: Ellen D. Ketterson.

Honorary Lifetime Membership Award: Ellen D. Ketterson.

A brain for all seasons: An in vivo MRI perspective on songbirds.

Seasonality in songbirds includes not only reproduction but also seasonal changes in singing behavior and its neural substrate, the song control system (SCS). Prior research mainly focused on the role of sex steroids on this seasonal SCS neuroplasticity in males. In this review, we summarize the advances made in the field of seasonal neuroplasticity by applying in vivo magnetic resonance imaging (MRI) in male and female starlings, analyzing the entire brain, monitoring birds longitudinally and determining the neuronal correlates of seasonal variations in plasma hormone levels and song behavior. The first MRI studies in songbirds used manganese enhanced MRI to visualize the SCS in a living bird and validated previously described brain volume changes related to different seasons and testosterone. MRI studies with testosterone implantation established how the consequential boost in singing was correlated to structural changes in the SCS, indicating activity-induced neuroplasticity as song proficiency increased. Next, diffusion tensor MRI explored seasonal neuroplasticity in the entire brain, focusing on networks beyond the SCS, revealing that other sensory systems and even the cerebellum, which is important for the integration of sensory perception and song behavior, experience neuroplasticity starting in the photosensitive period. Functional MRI showed that olfactory, and auditory processing was modulated by the seasons. The convergence of seasonal variations in so many sensory and sensorimotor systems resembles multisensory neuroplasticity during the critical period early in life. This sheds new light on seasonal songbirds as a model for unlocking the brain by recreating seasonally the permissive circumstances for heightened neuroplasticity.

Effect of Dietary Methylseleninic Acid and Se-Methylselenocysteine on Carcinogen-Induced, Androgen-Promoted Prostate Carcinogenesis in Rats

Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models. However, we have shown that daily oral bolus administration of next-generation selenium forms, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) at 3 mg Se/kg body weight, inhibits prostate carcinogenesis in the TRAMP and pten-deficient mouse models and In Vivo growth of human prostate cancer cells. Here, we determined whether these Se forms prevent prostate cancer in a chemically induced-androgen promoted carcinogenesis rat model in which SeMet was not preventive. WU rats were treated with methylnitrosourea, and one week later, slow-release testosterone implants when they were randomized to groups fed AIN-93M diet supplemented with 3 ppm selenium as MSeA or MSeC or control diet. Mean survival, tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) and the incidence of tumors confined to dorsolateral and/or anterior prostate were not statistically significantly different among the groups. Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.

Long-term Hyperandrogenemia and/or Western-style Diet in Rhesus Macaque Females Impairs Preimplantation Embryogenesis.

Hyperandrogenemia and obesity are common in women with polycystic ovary syndrome, but it is currently unclear how each alone or in combination contribute to reproductive dysfunction and female infertility. To distinguish the individual and combined effects of hyperandrogenemia and an obesogenic diet on ovarian function, prepubertal female rhesus macaques received a standard control (C) diet, testosterone (T) implants, an obesogenic Western-style diet (WSD), or both (T + WSD). After 5 to 6 years of treatment, the females underwent metabolic assessments and controlled ovarian stimulations. Follicular fluid (FF) was collected for steroid and cytokine analysis and the oocytes fertilized in vitro. Although the T + WSD females exhibited higher insulin resistance compared to the controls, there were no significant differences in metabolic parameters between treatments. Significantly higher concentrations of CXCL-10 were detected in the FF from the T group, but no significant differences in intrafollicular steroid levels were observed. Immunostaining of cleavage-stage embryos revealed multiple nuclear abnormalities in the T, WSD, and T + WSD groups. Single-cell DNA sequencing showed that while C embryos contained primarily euploid blastomeres, most cells in the other treatment groups were aneuploid. Despite yielding a higher number of mature oocytes, T + WSD treatment resulted in significantly reduced blastocyst formation rates compared to the T group. RNA sequencing analysis of individual blastocysts showed differential expression of genes involved in critical implantation processes between the C group and other treatments. Collectively, we show that long-term WSD consumption reduces the capacity of fertilized oocytes to develop into blastocysts and that the addition of T further impacts gene expression and embryogenesis.

A NEW approach for characterizing mouse urinary pathophysiologies.

The void spot assay (VSA) is a cost‐effective method for evaluating and quantifying mouse urinary voiding phenotypes. The VSA has been used to differentiate voiding behaviors between experimental groups, but not as a diagnostic assay. To build toward this goal, we used the VSA to define voiding patterns of male mice with diabetic diuresis (BTBR.Cg‐Lep ob /WiscJ mice), irritative urinary dysfunction (E. coli UTI89 urinary tract infection), and obstructive urinary dysfunction (testosterone and estradiol slow‐release implants) compared to their respective controls. Many studies compare individual VSA endpoints (urine spot size, quantity, or distribution) between experimental groups. Here, we consider all endpoints collectively to establish VSA phenomes of mice with three different etiologies of voiding dysfunction. We created an approach called normalized endpoint work through (NEW) to normalize VSA outputs to control mice, and then applied principal components analysis and hierarchical clustering to 12 equally weighted, normalized, scaled, and zero‐centered VSA outcomes collected from each mouse (the VSA phenome). This approach accurately classifies mice based on voiding dysfunction etiology. We used principal components analysis and hierarchical clustering to show that some aged mice (>24 m old) develop an obstructive or a diabetic diuresis VSA phenotype while others develop a unique phenotype that does not cluster with that of diabetic, infected, or obstructed mice. These findings support use of the VSA to identify specific urinary phenotypes in mice and the continued use of aged mice as they develop urinary dysfunction representative of the various etiologies of LUTS in men.

Correction to: Testosterone Implant Therapy in Women With and Without Breast Cancer: Rationale, Experience, Evidence by Glaser and Dimitrakakis Androg Clin Res Ther. 2021;2:94–110. DOI: 10.1089/andro.2021.0003.

Correction to: <i>Testosterone Implant Therapy in Women With and Without Breast Cancer: Rationale, Experience, Evidence</i> by Glaser and Dimitrakakis Androg Clin Res Ther. 2021;2:94–110. DOI: 10.1089/andro.2021.0003.

Testosterone Implant Therapy in Women With and Without Breast Cancer: Rationale, Experience, Evidence

Testosterone (T) is the most abundant biologically active hormone in women. It has a direct effect at the androgen receptor in every major organ system. Local aromatization of T is a major source of bioavailable estradiol. Adequate amounts of bioavailable T are essential for optimal health, immune function, and disease prevention. More than 80% of bioavailable T in women is from the local intracrine production of T from the adrenal precursor steroids androstenedione and dehydroepiandrosterone (sulfate). Serum T levels reflect <20% of the total androgen pool in women, which limits its usefulness in diagnosing or treating androgen deficiency. The gradual decline of androgens associated with aging is responsible for many of the adverse signs and symptoms of aging, including mental and physical deterioration. Decades of evidence support the safety and efficacy of T therapy in women. We have found that subcutaneous T implant therapy relieves symptoms of hormone deficiency in women with and without breast cancer, improves their quality of life, and maintains overall health and well-being. T does not increase and may lower the risk of breast cancer. The combination of T with an aromatase inhibitor prevents the conversion of androgens to estrogens, limiting their stimulatory effect in estrogen-sensitive diseases, including breast cancer. Adequate doses of T therapy should provide adequate levels of bioavailable T in the target organs—determined by clinical response (benefits) versus adverse side effects (risks). Pharmacological dosing of T implants in women is safe and necessary for physiological effect.

Portomesenteric venous thrombosis in a postmenopausal female with testosterone implant: a case report

BackgroundAcute portal vein thrombosis is a rare medical event usually seen in liver disease, but it can also occur due to any inherited or acquired procoagulable state that triggers venous occlusion. Hormonal therapies have been associated with an increased risk of prothrombotic states. This case report documents a portomesenteric venous thrombosis in a postmenopausal woman with testosterone implant for the treatment of hypoactive sexual desire and discusses the importance of identifying hypercoagulable risk factors before initiating hormone replacement therapy. We want to improve the awareness of an unusual medical complication associated with hormone replacement therapy and shed light on how testosterone implants could facilitate a thrombotic event related to other risk factors such as obesity and chronic hypoxic states, as well as the importance of differential diagnosis in the evaluation of postmenopausal women on testosterone replacement therapy presenting with acute abdominal pain.Case presentationA 55-year-old obese postmenopausal Hispanic female with medical history of chronic obstructive pulmonary disease presents with intractable abdominal pain, is found to have elevated hemoglobin and hematocrit, and an abdominopelvic computed tomography scan revealing portal and superior mesenteric vein thrombosis. Further evaluation excluded inherited and acquired thrombophilia but revealed elevated testosterone levels. The patient was treated with anticoagulation, which resulted in recanalization of the portal and superior mesenteric veins.ConclusionSupraphysiologic levels of testosterone caused by testosterone implants as a treatment of hypoactive sexual desire in postmenopausal women can contribute to thrombotic events in the presence of additional prothrombotic risk factors. Therefore, testosterone therapy should include a thorough risk assessment for prothrombotic states, be tailored to patients’ physiologic testosterone levels, and have close follow-up with testosterone level monitoring.

Placental Glucose Uptake in a Nonhuman Primate Model of Western-Style Diet Consumption and Chronic Hyperandrogenemia Exposure.

We reported that consumption of a western-style diet (WSD) with and without hyperandrogenemia perturbed placental perfusion and altered levels of glucose transporter proteins in rhesus macaques. Based on that result, we hypothesized that placental glucose uptake would be dysregulated in this model. In this study, female rhesus macaques were assigned at puberty to one of four groups: subcutaneous cholesterol implants + standard chow diet (controls, C); testosterone implants + chow (T); cholesterol implants + a high-fat, WSD; and T+WSD. After ~6 years of treatment, animals were mated, and pregnancies were delivered by cesarean section at gestational day (G) 130 (the term is G168). Placental villous explants were immediately prepared for radiolabeled glucose assay. Linear glucose uptake was observed between 0 and 30 s. At 20 s, glucose uptake in placental villous explants did not differ across the four treatment groups with values as follows: C: 25.5 ± 6.33, T: 22.9 ± 0.404, WSD: 26.9.0 ± 3.71, and T+WSD: 33.0 ± 3.12 (mean ± SD expressed in pmol/mg). Unlike our prior experiment, glucose transporter expression was reduced in WSD placentas, and our in vitro functional assay did not demonstrate a difference in glucose uptake across the transporting epithelium of the placenta. Notably, maternal blood glucose levels were significantly elevated in animals chronically fed a WSD. This disparity may indicate differences in glucose utilization and metabolism by the placenta itself, as glucose transporter expression and circulating fetal glucose concentrations were comparable across all four groups in this pregnancy cohort.

Lessons learnt from the variation across 6741 family/general practices in England in the use of treatments for hypogonadism

We have previously reported rates of diagnosis of male hypogonadism in United Kingdom (UK) general practices. We aimed to identify factors associated with testosterone prescribing in UK general practice. We determined for 6741 general practices in England, the level of testosterone prescribing in men and the relation between volume of testosterone prescribing and (1) demographic characteristics of the practice, (2) % patients with specific comorbidities and (3) national GP patient survey results. The largest volume (by prescribing volume) agents were injectable preparations at a total cost in the 12-month period 2018/19 of £8,172,519 with gel preparations in second place: total cost £4,795,057. Transdermal patches, once the only alternative to testosterone injections or implants, were little prescribed: total cost £222,022. The analysis accounted for 0.27 of the variance in testosterone prescribing between general practices. Thus, most of this variance was not accounted for by the analysis. There was a strong univariant relation (r=.95, P<.001) between PDE5-I prescribing and testosterone prescribing. Other multivariant factors independently linked with more testosterone prescribing were as follows: HIGHER proportion of men with type 2 diabetes(T2DM) on target control (HbA1c≤58mmol/mol) and HIGHER overall practice rating on the National Patient Survey for good experience, while non-white ethnicity and socio-economic deprivation were associated with less testosterone prescribing. There were a number of comorbidity factors associated with less prescribing of testosterone (such as T2DM, hypertension and stroke/TIA). Our analysis has indicated that variation between general practices in testosterone prescribing in a well developed health economy is only related to small degree (r2 =0.27) to factors that we can define. This suggests that variation in amount of testosterone prescribed is largely related to general practitioner choice/other factors not studied and may be amenable to measures to increase knowledge/awareness of male hypogonadism, with implications for men's health.

Physiological costs and age constraints of a sexual ornament: an experimental study in a wild bird

Abstract Sexual ornaments are often considered honest signals of quality because potential costs or constraints prevent their display by low-quality individuals. Testing for potential physiological costs of ornaments is difficult, as this requires experimentally forcing individuals to produce and display elaborate ornaments. We use this approach to test whether a sexually selected trait is physiologically costly to male superb fairy-wrens (Malurus cyaneus). Male fairy-wrens molt from brown to blue breeding plumage at different times of the year, and females strongly prefer the few males that are blue early, during winter. We used short-acting testosterone implants to stimulate males to produce “early-blue” plumage and assessed costs during and after molt using a panel of physiological indices. Testosterone-implanted, T-males molted in winter and produced blue plumage 6 weeks before control-implanted, C-males. T-males molted while in lower body condition, tended to have lower fat reserves, and were more likely to be parasitized by lice. However, we detected no negative effects on immune function, blood parasites, exposure to stressors, or survival. Juvenile males never naturally display early-blue plumage, but we found no evidence for increased costs paid by juvenile T-males. Instead, juvenile T-males molted later than adult T-males, suggesting that age presents an absolute constraint on ornament exaggeration that cannot be fully overcome by testosterone treatment. Together, these small costs and large, age-related constraints may enforce signal honesty, and explain female preference for early-blue males.