Testosterone Supplementation Research Articles

Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement

BackgroundSex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men’s health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men’s cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening.MethodsWe used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics.ResultsArterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress–strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression.ConclusionTestosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.Graphical

Testosterone: A Review for Orthopaedic Surgeons.

» Testosterone replacement treatment (TRT) and anabolic androgenic steroid (AAS) use is common and possibly increasing.» Diagnosing and treating hypogonadism in men is controversial.» Hypogonadism and the use of AASs seem to have a detrimental effect on the musculoskeletal system. The current literature on TRT and the musculoskeletal system shows an increased risk of tendon injury.» There may be a role for testosterone supplementation in the postoperative period.

Exogenous testosterone use and acute central serous chorioretinopathy in a transgender patient

Purpose: To describe the presentation and clinical course of a transgender patient with central serous chorioretinopathy (CSCR) and discuss the role of exogenous testosterone use in CSCR in this patient population. Method: Case report. Results: A 63-year-old transgender male with a history of exogenous testosterone use for over twenty years was referred to retina clinic for evaluation of macular pathology. The patient’s most recent total testosterone levels prior to presentation were 962 and 1,179 ng/dL (normal cisgender male levels for age 60+: 300-720 ng/dL). Fundus imaging revealed subretinal fluid involving the fovea without choroidal neovascularization in the right eye. There was no recent corticosteroid use. The patient’s dose of testosterone was reduced. After four months of observation, the subretinal fluid persisted and was successfully treated with half-fluence photodynamic therapy (PDT). At last follow-up, 15 months after PDT, the patient remained stable without recurrence and the best-corrected visual acuity was at baseline. Conclusion: Exogenous testosterone use with elevated serum testosterone levels may be associated with the development of central serous chorioretinopathy in the transgender patient population. CSCR in these patients might be effectively treated with PDT and testosterone dose reduction. Ophthalmologists should be aware of potential side effects of testosterone supplementation in this patient population, as well as the role of testosterone in CSCR pathophysiology.

Sex hormone supplementation improves breathing and restores respiratory neuroplasticity following C2 hemisection in rats.

In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17β-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2weeks post-SCI.

Sex Is Not a Transcriptomic Binary: Towards a Broad Physiologic Omics Insight Into Sex Chromosome Genes

Background: As social definitions of sex and gender expand, there is a greater demand for understanding the clinical challenges of intersex individuals, transgender individuals, and those with hormonal and transcriptomic profiles that do not align with traditional binary standards. Larger population studies are elucidating comorbidities associated with Klinefelter’s Syndrome, Turner’s Syndrome, 47XXX, 47XYY, and other sex chromosome syndromes even though the sex chromosomes are underpowered in traditional GWAS. Though research has focused on how estrogen and testosterone supplementation can influence comorbidity risk, we identify a need for greater understanding of isoform and tissue-specific expression and functions of X and Y genes to understand their potential interactions with hormones and inform physiological outcomes. Methods: Analysis of RNA-Sequencing data quantified in transcripts per million (TPM) from GTex (extracted June 2022, n = 17,382), NCBI SRA Blood PAXgene tube analysis (extracted June 2021, n = 12,559), and NCBI SRA “skin” RNA sequencing (extracted June 2021, n = 8,274). Results: We display an expression panel of 572 isoforms of 73 sex-biased genes across 54 male (n = 11,588) and female (n=5,798) tissue samples and highlight isoform-specific expression differences within the brain, arteries, heart, skeletal muscle, and gastrointestinal tract. Six X/Y gene pairs show broad ratios over tissues highlighting the role of X-chromosome dosage and X-chromosome inactivation escape differences in various tissues. Several genome-wide eQTLs across multiple tissues have sex differences and are found within X/Y chromosome transcription factor binding sites such as ZFX/ZFY. Stratifying blood and skin RNA-Sequencing data by XIST/KDM5D ratios to determine transcriptomic “sex”, we conduct an exploratory analysis of bioprojects with five or more outliers of X:Y chromosome expression ratios (Males: PRJNA683803 (HIV), PRJNA768419 (Sepsis), PRJNA492829 (Vaccine trial), PRJNA496323 (Psoriasis and atopic dermatitis), PRJNA699562 (COVID-19). Females: PRJNA683803 (HIV), PRJNA794277 (Sepsis), PRJNA492965 (Vaccine trial), PRJNA526259 (Myalgic encephalomyelitis)).Conclusion: Transcriptomics enables broader insights to sex chromosomes and their contributions to physiology outside of the binary male/female knowledge. This work was supported by the NIH NIAID and OD grant R01AI171984. This is the full abstract presented at the American Physiology Summit 2024 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.

Does testosterone supplementation improve sexual function in postmenopausal women?

Does testosterone supplementation improve sexual function in postmenopausal women?

Kisspeptin administration may promote precopulatory behavior in male rats independently or supplementally to testosterone and contribute to proceptive behavior in female partners, reducing mating failure

Kisspeptin is a peptide that plays an important role through its effects on the hypothalamus-pituitary–gonadal (HPG) axis. It has also been implicated in sexual behavior. The present study investigated whether the relationship between kisspeptin and sexual behavior is independent of the HPG axis, i.e., testosterone. Sexual behavior was examined after the administration of kisspeptin to gonadally intact male rats and gonadectomized male rats that received testosterone supplementation. Other male rats were also observed for sexual behavior once a week from 2 to 5 weeks after gonadectomy and receiving kisspeptin for the sixth postoperative week. Sexual behavior in female rats serving as the partner for each male was also observed. Female rats were not administered kisspeptin in the present study. The results obtained showed that the administration of kisspeptin increased precopulatory behavior in gonadally intact male rats and gonadectomized male rats that received testosterone supplementation and proceptive behavior in their female partners. Precopulatory behavior in males and receptive behavior in females increased, while copulatory behavior in males and receptive behavior in females remained unchanged. Furthermore, the administration of kisspeptin increased precopulatory behavior in gonadectomized males, but did not affect receptive behavior in females. These results suggest that kisspeptin affected males independently and/or supplementally to testosterone, and also that changes in the presence of testosterone in males had an impact on proceptive behavior in their female partners. In conclusion, kisspeptin may involve an as-yet-unidentified neural pathway in sexual desire independently of the HPG axis.

522 Testosterone Supplementation in Patients with Burn Hypermetabolism

Abstract Introduction After major burn injuries, patients experience a hypermetabolic response that leads to hyperdynamic circulatory, physiologic, catabolic, and immune system responses. Many transdisciplinary approaches have been tested to mitigate this postburn hypermetabolic syndrome such as comprehensive burn rehabilitation, nutritional support, monitoring, and pharmacological interventions. Oxandrolone, a synthetic analog of testosterone, has been shown to have higher anabolic properties and minimal androgenic effects and studied intensely in burn care. In 2023, the FDA asked all manufacturers of oxandrolone to cease production and subsequently removed the drug from market on June 28, 2023. Our study examines the cost and operationalization of an intramuscular (IM) testosterone protocol as an alternative in male burn patients with ≥20% total body surface area (TBSA). Methods A cost analysis was conducted using the National Drug Codes (NDC) and commercially available benchmarking data. The cost of oxandrolone and testosterone were included in our analysis. Following a thorough literature review, a protocol was developed for adult male patients with >20% TBSA burn injuries. Patients undergoing gender affirming hormone therapy, untreated obstructive sleep apnea, or hormonal blockers for cancer were excluded from the protocol. Results The protocol begins with total serum testosterone levels at the time of admission and weekly thereafter for male patients with ≥20% TBSA injury. Once a testosterone level < 150 ng/dL is detected, supplementation of testosterone with 200 mg IM once weekly for two weeks is started. Weekly evaluations include total body weight, metabolic panels, and nutritional panels. Cost comparison between oxandrolone and testosterone show an equivalent unit cost of $8.62 versus $8.38, respectively. Conclusions Drug shortages and supply chain challenges are becoming more common in burn care. We hypothesize testosterone to be both a clinically effective and cost-effective alternative to oxandrolone in the setting of burn hypermetabolism in male patients with major burns. Currently, burn experts are working with endocrinologists to assess pharmacologic alternatives for female patients and have obtained IRB-approval to evaluate both safety and efficacy of testosterone supplementation in the setting of burn hypermetabolism. Applicability of Research to Practice This study evaluates the safety and efficacy of testosterone supplementation as an alternative to oxandrolone in the setting of burn hypermetabolism. This study helps provide guidance to other burn centers in filling the gap in therapy that now exists in the pharmacologic management of hypermetabolic syndrome in patients with severe burns.

Testosterone Supplementation Promotes Estrogen Synthesis of Buffalo Cumulus Cells Surrounding In Vitro-Matured Oocytes.

Cumulus cells (CCs) synthesize estrogens that are essential for follicular development. However, the effects of androgen on estrogen production in buffalo CCs remain unknown. In the present study, the impacts of testosterone on estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes were investigated. The results showed that testosterone supplementation improved both the expression levels of estrogen synthesis-related genes (CYP11A1, CYP19A1, and 17β-HSD) and the secretion levels of estradiol in buffalo CCs surrounding in vitro-matured oocytes. Furthermore, testosterone treatment enhanced the sensitivity of buffalo CCs surrounding in vitro-matured oocytes to follicle-stimulating hormone (FSH). This study indicated that testosterone supplementation promoted the estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes mainly through strengthening the responsiveness of CCs to FSH. The present study serves as a foundation of acquiring high-quality recipient oocytes for buffalo somatic cell nuclear transfer.

The implications of supraphysiological testosterone supplementation.

The implications of supraphysiological testosterone supplementation.

Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction: A literature review

AbstractErectile dysfunction (ED) is increasing in prevalence, with estimates that 50% of men between 40 and 70 years of age suffer from the disease. Due to a wide array of available medical interventions, significant focus has been put on combination therapies that can treat ED refractory to first‐line treatments such as phosphodiesterase 5 inhibitors (PDE5is). However, reviews evaluating monotherapy noninferiority and patient satisfaction of monotherapy versus combination therapy are lacking. A thorough PubMed search was performed to evaluate combination therapy in ED treatment. Articles published between January 2008 and June 2023 were reviewed, including randomized control trials, retrospective analyses, and cohort studies. Combination therapies included PDE5i plus another PDE5i, testosterone supplementation, α‐blockers, vacuum erectile devices, intracavernosal injections, and low‐intensity shockwave therapy. Based on this review, PDE5i monotherapy is not inferior to combination therapy and has increased satisfaction, convenience, and ease of use for patients with ED. Limitations of current literature on combination therapy include small sample size, limited data on patient satisfaction, possible biases, and limited follow‐up time. Further studies will need larger randomized control trials with follow‐up times greater than 1 year.

The relationship between hematologic malignancies on male hypogonadism: a scoping review.

The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature. In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM). This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone." The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density. There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.

Associations between serum testosterone levels and overactive bladder in women: a cross-sectional research of NHANES 2011 to 2016.

Androgen receptors are expressed in the pelvic floor and lower urinary tract. However, the association between serum testosterone and overactive bladder (OAB) in women remains unclear. This study aimed to investigate their association in a nationally representative population. In this cross-sectional study, we collected data on female participants older than 20years with serum total testosterone measurements and OAB questionnaires from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression models were used to analyze the relationship between testosterone and OAB in women. Data on 4991 women was analyzed in this study, of whom 25.9% had OAB symptoms. Women with lower serum testosterone had an increased frequency of urge urinary incontinence and nocturia compared to participants with enough testosterone. The multivariate logistic models showed that those women with a testosterone level less than 18.5ng/dL had significantly higher odds of OAB compared to those with a testosterone level greater than 18.5ng/dL [OR 95% CI = 1.271 (1.073-1.505), P = 0.0076]. Separate interaction analyses revealed no significant effect of age, BMI, diabetes, education, alcohol use and menopause on the association between serum testosterone and OAB. Sensitivity analyses demonstrated that additional variables (depression, stroke and stress urinary incontinence) had no significant effect on this relationship. Low serum testosterone is associated with an increased likelihood of OAB in women. This supports the potential therapeutic role of testosterone supplementation in women with OAB. Given the direct and indirect effects of testosterone on the pelvic floor and lower urinary tract, a potential mechanism for this relationship can be further explored in translational studies.

(209) Investigating if Polygamy is Associated with Higher Levels of Testosterone or Not

Abstract Introduction Introduction: in middle east countries polygamy is legal and common. While the majority of married men have only one wife, some of them have more than one wife. Objective Objectives: Its a common hypothesis among public that a man who has more than one wife at a time is hypersexual and has higher levels of testosterone. We ran this study to check if this hypothesis is true or not. Methods We prospectively enrolled men who attended the andrology clinic for different reasons in this study in one-year duration. Exclusion criteria were: being single, age >45, body mass index (BMI) >30 or <20, diabetics, dyslipidaemia, pituitary dysfunction, thyroid dysfunction, cryptorchidism, history of primary infertility or azoospermia and testosterone supplementation. All patients had thorough medical history and marital status. Number of children of each participant was also recorded. All patients had blood sample for total testosterone between 9–11 am. Statistical analysis was performed using the T- Student test. Serum testosterone was compared in a multivariate analysis to martial history and number of children. Results 214 men were included in this analysis. The mean age was 28(19–45).98 patients had one wife (46%),43 had two wives (20%),37 had 3 wives (17.2%), and 36 had 4 wives (16.8%) at the time of presentation. The average number of children for each man was 4(1–17). The mean serum total testosterone was 4.6 ng/ml (3.2–7.6). The number of children was correlated with the number of wives (r=0.522, P<0.01). The number of children was negatively correlated with the testosterone level (r=-0.170, P<0.05). The number of wives was negatively correlated with the testosterone level (r=-0.180, P<0.01), see table 1.Once age has been controlled for, the correlation disappeard, see table 2. Conclusions Increasing numbers of both wives and children are not associated with higher levels of testosterone. Disclosure No.

Genistein and Sex Hormone Supplementation Modulated Hepatic PPARα, δ, and γ Subtypes and STAT1 Expressions in a NASH Rat Model with Bilateral Orchidectomy.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatic inflammation and steatosis. Currently, limited data exist regarding the risk of NASH in transgender women and the treatment options for this particular population. The use of testosterone supplementation is unfavorable for transgender women, and estrogen supplementation is linked to an increased risk of breast cancer; thus, an isoflavone derivative compound known as "genistein" could serve as a viable substitute for a hormone supplement in this context. The purpose of this study was to investigate the treatment effects and mechanisms of actions of genistein and sex hormones in orchidectomized (ORX) rats with nonalcoholic steatohepatitis induced via a high-fat high-fructose diet (HFHF) model. Male Sprague-Dawley rats (n = 42) were randomly assigned into seven groups; control, ORX + standard diet, HFHF, ORX + HFHF, ORX + HFHF diet + testosterone (50 mg/kg body weight (BW) once weekly), ORX + HFHF diet + estradiol (1.6 mg/kg BW daily), and ORX + HFHF diet + genistein (16 mg/kg BW daily). The duration of the study was 6 weeks. Some parts of liver tissue were used for histological examination by H&E staining. The determination of fat accumulation was performed using Oil Red O staining. SREBP1c and FAS gene expression were quantified using real-time PCR technique. The levels of all types of peroxisome proliferator-activated receptors (PPARs; α, δ, γ), proteins, and signal transducer and activator of transcription 1 (STAT1) signaling pathway were determined by both immunoblotting and immunohistochemistry. Rats in the ORX + HFHF group had the highest degree of hepatic steatosis, lobular inflammation, and hepatocyte ballooning, and showed higher levels of genes related to de novo lipogenesis, including SREBP1c and FAS. The expression of PPARγ and STAT1 were upregulated, while the expression of PPARα and PPARδ were downregulated in the ORX + HFHF group. Testosterone, estradiol and genistein treatments improved NASH histopathology together with the reversal of all types of PPAR protein expressions. Interestingly, genistein decreased the levels of STAT1 protein expression more than those of testosterone and estradiol treatment. Genistein and sex hormone treatment could ameliorate NASH through the upregulation of PPARα, and PPARδ, and the suppression of PPARγ and STAT1 expression.

(328) The Relationship Between Multiple Myeloma and Hypogonadism: A Systematic Review

Abstract Introduction Hypogonadism has been reported with substantial frequency in patients with various types of malignancies. Multiple myeloma (MM) is a cancer that affects plasma cells, a type of white blood cell responsible for producing antibodies. It is the second most common blood cancer, accounting for approximately 10% of hematologic malignancies. However, the prevalence, pathophysiology, and significance of hypogonadism as a sequela of MM or its standardized treatment regimens has not been extensively studied. Objective To characterize the existing literature on hypogonadism in patients with MM, including the prevalence, underlying mechanisms, and link to overall disease prognosis. Furthermore, we will examine the effects of testosterone therapy on MM and its hypogonadal symptomatology. Methods Relevant studies published up to November 2022 were retrieved through a search of PubMed using the keywords ‘hypogonadism’, ‘multiple myeloma’, and ‘testosterone’. Studies that reported on the presentation, management, or outcomes of patients with MM and how they were affected by a hypogonadal state were included. The search yielded 72 studies, of which 11 met the inclusion criteria. Results The most comprehensive assessment of the frequency of hypogonadism in a MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Further evaluation found that male patients with MM were found to have significantly lower levels of testosterone than control (p<0.0001). Another assessment of hormone level differences between MM patients and controls found that male patients had higher: FSH, LH, estrogen, and E/T ratios than healthy controls. Testosterone supplementation was found to lower interleukin-6 (IL-6) levels, which could potentially contribute to the adverse effects of MM. This effect could arise from the finding that IL-6 concentration was independently associated with severe symptomatology in MM patients on multivariate analysis in a study by Wang et al. (p=0.004). Hypogonadism can occur as an adverse effect of MM treatment with immunotherapy/chemotherapy initiation. A small study by Greenfield et al. found that 65% of patients intensively treated for MM were subsequently hypogonadal. This was further supported by a study by Anderson et al. examining sexual function after autologous hematopoietic stem cell transplant (AHSCT), which saw a significant increase in erectile dysfunction at 1-month follow-up from 68.4% to 100% of all patients. Conclusions There appears to be a relationship between MM and hypogonadism, potentially due to the inflammatory state caused by the disease itself. This may have some association with the inflammatory cytokine IL-6. However, there is a paucity of data fully exploring this relationship, the underlying mechanisms, and the effects of testosterone therapy on MM. The true relationship is likely multifactorial, given the mixture of studies that found hypogonadism in MM at baseline as well as after systemic treatment. Future prospective and randomized studies are necessary to elucidate the true link between MM and/or its treatment and hypogonadism. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Hims & Hers Inc, Coloplast, Clarus Therapeutics, Antares Pharma, Acerus.

Use of transdermal testosterone in women Poseidon IV group under high complexity assisted reproduction treatment

Poor ovarian reserve (POR) is considered a frequent cause of infertility and is still considered one of the significant challenges in reproductive medicine. Numerous studies have suggested that androgens (dehydroepiandrosterone and testosterone) may play a critical role in follicular development by increasing the number of follicles and, consequently, the number of oocytes, ultimately leading to an increased pregnancy rate. Testosterone is a sex steroid hormone that originates from cholesterol and is considered an obligatory precursor of estradiol biosynthesis. It contributes to greater follicular recruitment, leading to the consideration that exogenous administration could increase the number of recovered oocytes. Methodology A historical, quantitative, observational, longitudinal, retrolective cohort study was carried out in the clinical area of assisted reproduction; 2 groups were formed where all women over 35 with primary or secondary infertility who met the criteria were included. Classification criteria of the POSEIDON IV group (age > 35 years with CFA < 5 follicles and/or AMH < 1.2 ng/mL), during the period from October 2021 to September 2022, the first group of patients had received supplementation with transdermal Testosterone 50mg daily one month before ovarian stimulation, the second group did not receive any treatment before ovarian stimulation. Women with a history of diagnosis of endometriosis, pelvic surgery or oophorectomy were excluded. This study has the approval of the ethics committee of the HISPAREP clinic. Each patient was given an informed consent which they signed before the study. We declare that we have no conflict of interest. The data from the records of all the patients who met the inclusion criteria were collected, including the antral follicle count on the first three days of the menstrual cycle by transvaginal ultrasound one month before ovarian stimulation and after one month of supplementation and without supplementation when starting controlled ovarian stimulation. The number of metaphase II oocytes obtained in each group was also analyzed. Results A total of 20 women were included; 10 underwent controlled ovarian stimulation with prior administration of transdermal testosterone at a dose of 50 mg every 24 hours for one month. The other 10 patients did not receive any supplementation or treatment before ovarian stimulation for highly complex assisted reproduction treatment due to various causes of infertility. The average age of the women was 40.2 ± 2.5 years in the study group and 43.3 ± 2 in the control group; normal weight in 80% of the group with testosterone and 90% without testosterone. The baseline conditions of the patients revealed an average anti-Müllerian hormone (AMH) level of 0.65 ± 0.28 ng/dL in the testosterone group and 0.84 ± 0.49 ng/dL in the non-testosterone group. The infertility factor was ovarian endocrine dysfunction, present in 60% of the testosterone group and 40% of the non-testosterone group; this factor was the predominant cause in both groups. The most common protocol stimulation was with (300/150 U) FSH/LH recombinant (Pergoveris, Merck) and GnRH antagonist (Cetrotide, Merck). The antral follicular count observed by ultrasound in each group after treatment with testosterone was 6.4 ± 2.4, and without testosterone was 6 ± 3.47; p<0.778. Without observing significant differences. The number of metaphase II oocytes obtained (mean ± standard deviation) after testosterone administration was 4.5 ± 2.37 and 1.5 ± 1.62 in participants who did not receive testosterone; p=0.04886, that is p<0.05, so the results were statistically significant in favor of testosterone administration. Conclusions Transdermal testosterone supplementation can be used as an adjuvant in controlled ovarian stimulation treatments in women of the POSEIDON IV group to improve the reproductive prognosis of this group of women. The 50mg dose of transdermal testosterone every 24 hours 1 month prior to the ovarian stimulation in highly complex treatments increases the number of metaphase II oocytes recovered statistically.

FSH Is Responsible for Androgen Deprivation Therapy-Associated Atherosclerosis in Mice by Exaggerating Endothelial Inflammation and Monocyte Adhesion.

Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer. But ADTs with orchiectomy and gonadotropin-releasing hormone (GnRH) agonist are associated with increased risk of cardiovascular diseases, which appears less significant with GnRH antagonist. The difference of follicle-stimulating hormone (FSH) in ADT modalities is hypothesized to be responsible for ADT-associated cardiovascular diseases. We administered orchiectomy, GnRH agonist, or GnRH antagonist in male ApoE-/- mice fed with Western diet and manipulated FSH levels by testosterone and FSH supplementation or FSH antibody to investigate the role of FSH elevation on atherosclerosis. By combining lipidomics, in vitro study, and intraluminal FSHR (FSH receptor) inhibition, we delineated the effects of FSH on endothelium and monocytes and the underlying mechanisms. Orchiectomy and GnRH agonist, but not GnRH antagonist, induced long- or short-term FSH elevation and significantly accelerated atherogenesis. In orchiectomized and testosterone-supplemented mice, FSH exposure increased atherosclerosis. In GnRH agonist-treated mice, blocking of short FSH surge by anti-FSHβ antibody greatly alleviated endothelial inflammation and delayed atherogenesis. In GnRH antagonist-treated mice, FSH supplementation aggravated atherogenesis. Mechanistically, FSH, synergizing with TNF-α (tumor necrosis factor alpha), exacerbated endothelial inflammation by elevating VCAM-1 (vascular cell adhesion protein 1) expression through the cAMP/PKA (protein kinase A)/CREB (cAMP response element-binding protein)/c-Jun and PI3K (phosphatidylinositol 3 kinase)/AKT (protein kinase B)/GSK-3β (glycogen synthase kinase 3 beta)/GATA-6 (GATA-binding protein 6) pathways. In monocytes, FSH upregulated CD29 (cluster of differentiation 29) expression via the PI3K/AKT/GSK-3β/SP1 (specificity protein 1) pathway and promoted monocyte-endothelial adhesion both in vitro and in vivo. Importantly, FSHR knockdown by shRNA in endothelium of carotid arteries markedly reduced GnRH agonist-induced endothelial inflammation and atherosclerosis in mice. FSH is responsible for ADT-associated atherosclerosis by exaggerating endothelial inflammation and promoting monocyte-endothelial adhesion.

Exploring the role of testosterone upon adiposity and cardiovascular risk markers in men with severe obesity

A prominent endocrine disorder linked to unhealthy lifestyle behaviors and increased visceral adiposity is Male Obesity Secondary Hypogonadism (MOSH). The pathogenesis of MOSH remains under investigation. However, recent evidence supports a direct role of leptin in affecting Leydig cells, reducing testosterone production, and increasing appetite. Conversely, testosterone deficiency is associated with comorbidities like hypertension, diabetes, and nonalcoholic fatty liver disease. A recently published study entitled “Relationship between sex hormones, markers of adiposity and inflammation in male patients with severe obesity undergoing bariatric surgery” describes evidence supportive of an inverse association between testosterone and serum leptin as well as levels of c-reactive protein (CRP) and IL-6, as well as a correlation between body mass index and CRP. The same study also provides novel insight retrieved from their in vitro findings, which reveal that testosterone exposure influences the expression of genes associated with adiposity, like fatty acid binding protein 4, peroxisome proliferation-activated receptor γ (PPARγ), leptin, and adiponectin, as well as von Willebrand factor, in human-derived adipocytes. Overall, the latest evidence highlights the importance of early identification of hypogonadism in obese males and the potential benefits of testosterone supplementation in alleviating complications associated with obesity, particularly chronic inflammation. These observations underscore the need for a holistic approach to managing severe obesity, addressing hormonal and inflammatory factors to reduce its overall burden on health.

Testosterone regulates thymic remodeling by altering metabolic reprogramming in male rats

The thymus is an energy-consuming organ, and its metabolism changes with atrophy. Testosterone regulates thymus remodeling (atrophy and regeneration). However, the characteristics of the energy metabolism during testosterone-mediated thymic atrophy and regeneration remain unclear. In this study, we demonstrated that testosterone ablation (implemented by immunocastration and surgical castration) induced global metabolic changes in the thymus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment for differential metabolites and metabolite set enrichment analysis for total metabolites revealed that testosterone ablation affected thymic glycolysis, glutamate metabolism, and fatty acid β-oxidation. Testosterone ablation-induced thymic regeneration was accompanied by attenuated glycolysis and glutamate metabolism and changed fatty acid composition and content. Testosterone supplementation in immunocastrated and surgically castrated rats enhanced glutaminolysis, reduced the level of unsaturated fatty acids, enhanced the β-oxidation of unsaturated fatty acids in the mitochondria, boosted the tricarboxylic acid (TCA) cycle, and accelerated thymic atrophy. Overall, these results imply that metabolic reprogramming is directly related to thymic remodeling.