Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Insights on Protective Effect of Platelet Rich Plasma and Tadalafil on Testicular Ischemia/Reperfusion Injury in Rats Exposed to Testicular Torsion/Detorsion.

BACKGROUND/AIMS: Ischemic reperfusion (I-R) injury is greatly influenced by the testicular torsion/detorsion process (TDP). In this instance, the anti-inflammatory properties of plateletrich plasma (PRP) combined with tadalafil (Td) significantly promote tissue healing in the I-R injury model. METHODS: Five groups of rats were created: the control group, the I-R group not receiving any therapy, the I-R group receiving a single dosage of Td (0.25 mg/kg, I.P.), the I-R group receiving a single dose of PRP (80 l, intratesticular), and the I-R group receiving both Td and PRP. Sperm morphology, motility, and histology were assessed. The levels of TNF-, BAX, antioxidant status, and testosterone were measured. Additionally, E-selectin expression was done. RESULTS: PRP reduced oxidative stress, inflammation, and apoptosis while also boosting testosterone levels, which alleviated I-R injury. Otherwise, PRP reduces E-selectin expression, which modifies the pathways that control endothelial function. Td also partially demonstrated its testicular-protective activity at the same time. CONCLUSION: PRP's proven anti-inflammatory, antioxidant, and antiapoptotic potentials make it a natural treatment for testicular harm caused by tadalafil. For the first time, it was demonstrated that PRP therapy restored the functionality of the vascular endothelium, specifically the control of E-selectin expression. Combining Td and PRP therapy may be a promising strategy for improving response to PDE5 inhibitors.

Pathophysiology of obesity-related infertility and its prevention and treatment by potential phytotherapeutics.

BACKGROUND: Obesity is a complex multifactorial disease in which the accumulation of excess body fat has adverse health effects, as it can increase the risk of several problems, including infertility, in both men and women. Obesity and infertility have risen together in recent years. Against this background, the present review aims to highlight the impact of obesity on infertility and the underlying pathophysiology of obesity-related infertility (ORI) in men and women, and to provide readers with knowledge of current trends in the effective development of phytotherapeutics for its treatment. METHODS: We thoroughly searched in PubMed, MEDLINE, Scopus, EMBASE, and Google Scholar to find all relevant papers on ORI and the therapeutic effects of phytotherapeutics on ORI in men and women. RESULTS: The extensive search of the available literature revealed that obesity affects reproductive function through several complex mechanisms such as hyperlipidaemia, hyperinsulinaemia, hyperandrogenism, increased body mass index, disruption of the hormonal milieu, systemic inflammation, oxidative stress, alterations in epigenetics and dysbiosis. On the other hand, several studies reported that phytotherapeutics has a broad therapeutic spectrum of action by improving sex hormone homeostasis, ovarian dysfunction, menstrual cycle and inhibiting ovarian hyperplasia, as well as down-regulating ovarian apoptosis, inflammation and oxidative stress, and controlling metabolic dysfunction in obese women. Male infertility is also addressed by phytotherapeutics by suppressing lipogenesis, increasing testosterone, 3ß-HSD and 17ß-HSD levels, improving sperm parameters and attenuating testicular dyslipidaemia, oxidative stress, inflammation and germ cell apoptosis. CONCLUSIONS: In the present review, we discussed the effects of obesity on reproductive dysfunction in men and women and the underlying pathophysiology of ORI. In addition, the therapeutic effect of phytotherapeutics against ORI was highlighted.

Arrhythmogenic substrate elimination for safe testosterone therapy in symptomatic Brugada syndrome patients.

BACKGROUND: Brugada Syndrome (BrS) is a cardiogenetic disease known for its association with sudden cardiac death (SCD) in individuals with structurally normal hearts. The prevalence of BrS is higher in males, who also face a greater risk of SCD. Its higher prevalence and worse outcome in male subjects may be due to testosterone effects on ion channels expression and function. The influence of testosterone on cardiac action potentials, both genomically and non-genomically, underscores its potential role in unmasking the syndrome and triggering life-threatening arrhythmias. Notably, testosterone replacement therapy (TRT), used for hypogonadism and gender reassignment, has been linked to BrS unmasking. The role of epicardial ablation in symptomatic BrS patients where hormonal therapy cannot be discontinued is unknown. METHODS AND RESULTS: In this study we describe the first two cases of substrate mapping and ablation in BrS patients experiencing arrhythmic events while on TRT. In both cases, high-density epicardial mapping revealed abnormal areas of prolonged and fragmented electrograms in the right ventricular (RV) outflow tract and anterior wall. These abnormalities were completely abolished by radiofrequency ablation (RFA). After ablation, both patients showed a persistent normalization of the ECG and were free from ventricular arrhythmias at follow-up, despite ongoing TRT. CONCLUSION: RFA can be considered as a therapeutic option in symptomatic BrS patients with a high-risk profile who cannot discontinue TRT, being essential for restoring their normal physiology or preserving their sexual identity. As testosterone use is increasing, further studies are warranted to define a standardized diagnostic and therapeutic strategy in this specific subset of BrS patients.

Quantifying Glans Width Changes in Response to Preoperative Androgen Stimulation in Patients Undergoing Hypospadias Repair.

PURPOSE: Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery. MATERIALS AND METHODS: Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated. RESULTS: A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p <0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p <0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p <0.001). A histogram plot revealed the distribution of GW change at surgery. CONCLUSIONS: In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.

Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone.

BACKGROUND: In the context of established male hypogonadism, testosterone therapy (TTh) has been employed to regain physiologic levels of circulating testosterone and improve sexual function and overall quality of life. AIM: To assess the risk of cardiovascular disease and mortality as time-dependent outcomes in treated vs TTh untreated hypogonadal men. METHODS: A meta-analysis using weighted time-related measure of risk (hazard ratios (HRs)) for each of the outcome for all included studies was performed. Studies investigating male adults (≥18 years old) diagnosed with hypogonadism and divided into 2 arms (a treatment arm [any TTh] and a control arm [observation or placebo]) and assessing the risk of death and/or cardiovascular events were included. Single arm, non-comparative studies were excluded as well as studies that did not report the HRs for the chosen outcomes. This systemic review was registered on PROSPERO (CRD42022301592) and performed according to MOOSE and PRISMA guidelines. OUTCOMES: Overall mortality and cardiovascular events of any type. RESULTS: Overall, 10 studies were included in the meta-analysis, involving 179,631 hypogonadal men. Hypogonadal men treated with TTh were found to be at lower mortality risk from all causes relative to the control (observation or palcebo) arm (HR: 0.70; 95% Confidence Interval [CI]: 0.54-0.90; P < .01), whilst any unfavorable effect of TTh in hypogonadal men in terms of cardiovascular events compared to untreated/observed hypogonadal men was found (HR: 0.98; 95% CI 0.73-1.33; P = .89). CLINICAL IMPLICATIONS: TTh in hypogonadal men might play a role in reducing the overall risk of death without increasing cardiovascular events risk. STRENGTHS & LIMITATION: Main limitations are represented by the high heterogeneity among the studies in terms of included population, definition for hypogonadism, type of TTh, definition of cardio-vascular event used, and the length of follow-up. CONCLUSION: According to time-related measures of risk only, an increased risk of long-term morbidity and early mortality for untreated hypogonadal men was depicted, further outlining the clinical importance and safety of TTh in true hypogonadal men, with the urgent need of collecting long-term follow-up data. Fallara G, Pozzi E, Belladelli F, et al. Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone. J Sex Med 2022;19:1243-1254.

How Would You Manage This Male Patient With Hypogonadism? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Male hypogonadism is defined as an abnormally low serum testosterone concentration or sperm count. As men age, often in the context of obesity and other comorbid conditions, serum testosterone levels may decrease. Normalizing serum testosterone levels in male adults with hypogonadism may improve symptoms related to androgen deficiency, but controversies exist regarding the long-term benefits and risks of hormone supplementation in this setting. In 2020, the American College of Physicians published a clinical guideline for the use of testosterone supplementation in adult men based on a systematic review of available evidence. Among their recommendations were that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function and not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. Here, two clinicians with expertise in this area, one a generalist and the other an endocrinologist, debate the management of a patient with sexual symptoms and a low serum testosterone level. They discuss the diagnosis of male hypogonadism, the indications for testosterone therapy, its potential benefits and risks, how it should be monitored, and how long it should be continued.

Evidence-Based Contraception: Common Questions and Answers.

Primary care clinicians are uniquely situated to reduce unintended pregnancy in the context of a patient's medical comorbidities, social circumstance, and gender identity. New evidence regarding contraception use has emerged in recent years. The copper intrauterine device is the most effective option for emergency contraception, with similar effectiveness found for the levonorgestrel-releasing intrauterine system, 52 mg, and both offer extended future contraception. Ulipristal given within 120 hours after unprotected intercourse is the most effective oral emergency contraceptive. Oral levonorgestrel, 1.5 mg, is slightly less effective than ulipristal, and is less effective in patients with a body mass index of more than 30 kg per m2 and if administered after 72 hours. The Yuzpe method, which uses a combination of oral contraceptives, is less effective than ulipristal or oral levonorgestrel, 1.5 mg, and has high risk of nausea and vomiting. Contraception methods based on fertility awareness are safe and have similar effectiveness as condom use and the withdrawal method. Patients who have migraine with aura have a higher risk of ischemic stroke, and combined oral contraceptives appear to increase this risk. Therefore, the Centers for Disease Control and Prevention recommends avoiding their use in these patients. Studies support the extended use of the levonorgestrel-releasing intrauterine system, 52 mg, for seven years, the copper intrauterine device for 12 years, and the etonogestrel subdermal contraceptive implant for five years. One levonorgestrel-releasing intrauterine device, 52 mg, (Mirena) was recently approved by the U.S. Food and Drug Administration (FDA) for seven years of use to prevent pregnancy. However, the intervals for the copper intrauterine device and the etonogestrel subdermal contraceptive implant are longer than approved by the FDA, and patient-clinician shared decision-making should be used. Subcutaneous depot medroxyprogesterone acetate, 104 mg, a newer formulation with prefilled syringes, can be safely self-administered every 13 weeks. Because bone density loss appears to be reversible, the American College of Obstetricians and Gynecologists recommends considering use of depot medroxyprogesterone acetate beyond two years despite an FDA boxed warning about increased fracture risk. Testosterone does not prevent pregnancy but is safe to use with hormonal contraception; thus, transgender and gender-diverse patients with a uterus can be offered the full range of contraceptive options.

The evaluation of citral effects on experimental unilateral testicular ischemia/reperfusion injury.

This investigation aimed to evaluate the defensive impacts of citral on ischemia/reperfusion (I/R) injury induced by testicular torsion/detorsion (T/D) in rats in an experimental model. The grouping of subjects was as follows: (1) sham, (2) T/D, (3) and (4) T/D plus citral 150 and 300 mg/kg, respectively, and (5) intact (citral 300 mg/kg). T/D was performed by testicular 720° turning for 2 h and then detorsion for 24 h. Blood serum was obtained to assess testosterone and oxidative stress markers, epididymal sperms were collected for sperm staining and sperm analysis, and testicular tissues were examined for histopathology. T/D damage was associated with a remarkable decline in sperm total count, viability, and some velocity parameters in comparison to the sham group (p < 0.05), which could be reversed significantly by citral (p < 0.05). Histopathologically, T/D damage caused severe oedema, haemorrhage, inflammation, and seminiferous tubules disruption, while citral improved significantly the mean seminiferous tubular diameter, Cosentino's score, and Johnsen's score (p < 0.05). I/R injury was associated with significant increased malondialdehyde and oxidative stress index, and also significant reduced total antioxidant capacity and testosterone versus the sham group (p < 0.05), which all were prevented significantly by citral administration (p < 0.05). The outcomes greatly proved that testicular I/R injury could be significantly prevented by citral.

Gender-Affirming Mastectomy Trends and Surgical Outcomes in Adolescents.

Background: There are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system. Methods: Gender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests. Results: The incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively. Conclusion: Between 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy.

Quality of life in Klinefelter patients on testosterone replacement therapy compared to healthy controls: an observational study on the impact of psychological distress, personality traits, and coping strategies.

PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.

Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians.

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians. Methods: The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events. Target Audience and Patient Population: The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone. Recommendation 1a: ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences. Recommendation 1b: ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence). Recommendation 1c: ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar. Recommendation 2: ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).

A population K-PD model analysis of long-term testosterone inhibition in prostate cancer patients undergoing intermittent androgen deprivation therapy.

Intermittent androgen deprivation therapy with gonadotropin-releasing-hormone (GnRH) agonists can prevent or delay disease progression and development of castration resistant prostate cancer for subpopulations of prostate cancer patients. It may also reduce risk and severity of side effects associated with chemical castration in prostate cancer (PCa) patients. One of the earliest comprehensively documented clinical trials on this was reported in a Canadian patient population treated with leuprorelin preceded by a lead-in with cyproterone acetate. A systems-based mixed effect analysis of testosterone response in active and recovery phases allows inference of new information from this patient population. Efficacy of androgen deprivation therapy is presumed to depend on a treshold value for testosterone at the nadir, below which no additional beneficial effects on PSA reponse can be expected, and occurance of testosterone breakthroughs during active therapy. The present analysis results in a mixed effect model, incorporating GnRH receptor activation, testosterone turnover and feedback mechanisms, describing and predicting testosterone inhibition under intermittent androgen deprivation therapy on the individual and population level, during multiple years of therapy. Testosterone levels in these patients decline over time with an estimated first order rate constant of 0.083 year-1(T1/2 = 8.4 y), with a substantial distribution among this patient population, compared to the general population. PCa patients leaving the trial due to unmanageble PSA relapse appear to have slightly higher testosterone levels at the nadir than sustained responders. These findings are expected to contribute to an increased understanding of the role of testosterone in long term disease progression of prostate cancer.

Fathering behavior, attachment, and engagement in childcare predict testosterone and cortisol.

The present study examined testosterone (T) and cortisol (Cort) in fathers engaged with caregiving. We collected saliva samples in the mornings and evenings of two consecutive days in 150 fathers of 1- to 5-year-old children. Fathers completed questionnaires on socioeconomic status, family structure and life, sleep characteristics and body mass index (BMI), and reported on their engagement in childcare. Fathers used smartphone-based experience sampling throughout 1 week to sample ongoing activities with their children, including times of supervision, joint play, rough-and-tumble play, and cuddling episodes. External observers rated father-child attachment during a home visit. We began by testing for widely characterized covariates of T and excluded seasonal variations and known predictors associated with lowered T, such as older fathers and those with multiple and young children, lower BMI, shorter sleep duration, and sexual activity before sampling. Most interestingly, however, fathers' engagement in childcare and attachment to the child appeared more pronounced the greater the diurnal decline in T. Cuddling predicted a similar negative association, whereas joint play and rough-and-tumble play (RTP) showed enhancing effects on declining T. Interestingly, all fathering behaviors (except RTP) were positively related to lower Cort. In contrast, supervision was ineffective on both Cort and T.

[Current understanding of the role of age-related hypogonadism in the development of cardiovascular diseases].

The literature review presents novel data on the prevalence of age-related hypogonadism and its relationship with aging, its impact on the circulatory system and cardiovascular diseases. This review summarizes the methods for diagnosing age-related hypogonadism, its association with traditional cardiovascular risk factors such as dyslipidemia, insulin resistance and diabetes mellitus, obesity, arterial hypertension. The mechanisms of the possible direct effect of testosterone on endothelium and vascular tone, the role of hormone replacement therapy as a way of preventing cardiovascular diseases are discussed.

Life history and individual differences in male testosterone: Mixed evidence for early environmental calibration of testosterone response to first-time fatherhood.

Male testosterone (T) decreases in response to childbirth. Longitudinal support for this has come from samples across cultures. In this study, we look at individual differences in this phenomenon. Utilizing a sample of U.S. fathers, we employ life history theory to investigate the influence of a father's early experience on his neuroendocrine response to fatherhood. We conducted three home visits (n = 226 fathers) from the third trimester of pregnancy to when infants were 10 months old. In this sample, T declined from the third trimester of (a partner's) pregnancy to the early months of the postnatal period. T recovered to pre-birth levels by the time infants reached 10 months old. We did not find any evidence that one's subjective experience of their early environment could account for any meaningful variability in T calibration. Objective, "event" measures of early harshness (i.e., death of a sibling/friend) and unpredictability (i.e., parent upheaval) each uniquely predicted a younger age of sexual debut. Neither harshness nor unpredictability had any (direct or indirect) effects on T calibration. Age of sexual debut did predict the rate of T recovery from 3 to 10 months postnatal. The younger one's sexual debut, the more accelerated their T ascent during this period. We discuss the potential reasons for, and implications of our mixed results.

Contraception across the transmasculine spectrum.

The field of transgender health continues to expand rapidly, including research in the area of family planning. While much attention has been given to fertility preservation and the parenting intentions of transgender individuals, far less has been paid to pregnancy prevention and contraceptive needs of people along the transmasculine gender spectrum (transgender men and gender-nonbinary persons who were assigned female at birth). Existing research illustrates that many clinicians and transmasculine individuals falsely believe that there is no risk of pregnancy while amenorrheic. These studies also show inconsistent counseling practices provided to transmasculine persons surrounding contraception and pregnancy while falling short of providing robust clinical guidance for improvement. Clinicians report a lack of adequate training in transgender reproductive health, and consequently, many do not feel comfortable treating transgender patients. The aim of this publication is to consolidate the findings of these prior studies and build upon them to offer comprehensive clinical guidance for managing contraception in transmasculine patients. To do so, it reviews the physiologic effects of testosterone on the sex steroid axis and current understanding of why ovulation and pregnancy may still occur while amenorrheic. Gender-inclusive terminology and a suggested script for eliciting a gender-affirming sexual history are offered. Common concerns (such as the effects on gender dysphoria and gender affirmation) and side effects of available contraceptive methods are subsequently addressed and how these may have a unique impact on transmasculine persons as compared with cisgender women. Lastly, a model is provided for approaching contraceptive counseling in the transmasculine population to assist clinicians and patients in determining the need for and selection of the type of contraception. To center transmasculine voices, the development of this publication's guidelines have been led by reproductive care clinicians of transgender experience.