The probability of pregnancy in 100 episodes of sexual intercourse: A measure of male contraceptive performance.

Background: Accurately judging the efficacy of contraceptives is vital for preventing unintended pregnancy. The Pearl index and life table analysis describe female contraceptive performance. However, they are not ideal for quantifying male contraceptive efficacy given differences between male and female methods.

The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.

The retinoid nuclear receptor pathway, activated by the vitamin A metabolite retinoic acid, has been extensively investigated for over a century. This study has resulted in conflicting hypotheses about how the pathway regulates health and how it should be pharmaceutically manipulated. These disagreements arise from a fundamental contradiction: retinoid agonists offer clear benefits to select patients with rare bone growth disorders, acute promyelocytic leukemia, and some dermatologic diseases, yet therapeutic retinoid pathway activation frequently causes more harm than good, both through acute metabolic dysregulation and a delayed cancer-promoting effect.

Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets.

Sperm cryopreservation is important for many individuals across the globe. Recent studies show that vitrification is a valuable approach for maintaining sperm quality after freeze-thawing processes and requires sub-microliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample.

Emerging approaches to male contraception.

Background: Currently, approximately half of all pregnancies worldwide are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy; however, options for men are particularly limited. Consequently, efforts are underway to develop novel, safe, and effective male contraceptives.

Shared risk and shared responsibility: the ethics of male contraceptives.

Introduction: Efforts to develop reversible male contraceptives analogous to female oral contraceptives are underway and may be introduced in the next decade. The advent of novel male contraceptives provides an opportunity for an ethical reformulation of the contraceptive paradigm given the relational, rather than individual, nature of sexual relationships, and family planning. For individuals in any sexual relationship that could result in pregnancy, issues of reproductive autonomy, freedom, equality in reproductive decision-making and risks-both of side effects and of unintended pregnancies-are significant.

Determination of pharmacological inhibition of ALDH2 by ethanol clearance in mice.

Objectives: Retinoic acid plays diverse physiological and pathophysiological roles in reproduction, immune function, energy metabolism and carcinogenesis. Because of the potential benefits of inhibiting retinoic acid biosynthesis in certain disease states, efforts are underway to develop inhibitors of retinoic acid biosynthesis via inhibition of the aldehyde dehydrogenase-1 A (ALDH1A) family of enzymes. However, many potential ALDH1A inhibitors also inhibit the related ALDH2 enzyme that plays a role in the metabolism of ethanol.

Male Contraception.

Approximately 40 to 50% of pregnancies are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy. Approximately 70% of couples' contraceptive use is female and 30% is male, attributable to the reliance on condoms and vasectomies.

Practice and development of male contraception: European Academy of Andrology and American Society of Andrology guidelines.

Backgrounds: Despite a wide spectrum of contraceptive methods for women, the unintended pregnancy rate remains high (45% in the US), with 50% resulting in abortion. Currently, 20% of global contraceptive use is male-directed, with a wide variation among countries due to limited availability and lack of efficacy. Worldwide studies indicate that >50% of men would opt to use a reversible method, and 90% of women would rely on their partner to use a contraceptive.

Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone).

Injectable male hormonal contraceptives are effective for preventing pregnancy in clinical trials; however, users may prefer to avoid medical appointments and injections. A self-administered transdermal contraceptive gel may be more acceptable for long-term contraception. Transdermal testosterone gels are widely used to treat hypogonadism and transdermal administration may have utility for male contraception; however, no efficacy data from transdermal male hormonal contraceptive gel are available.

Relevance of Human Aldoketoreductases and Microbial -Glucuronidases in Testosterone Disposition.

Testosterone exhibits high variability in pharmacokinetics and glucuronidation after oral administration. Although testosterone metabolism has been studied for decades, the impact of UGT2B17 gene deletion and the role of gut bacterial -glucuronidases on its disposition are not well characterized. We first performed an exploratory study to investigate the effect of UGT2B17 gene deletion on the global liver proteome, which revealed significant increases in proteins from multiple biological pathways.

Evaluation and clinical validation of monkeypox (mpox) virus real-time PCR assays.

Background: In spring of 2022, an outbreak of monkeypox (mpox) spread worldwide. Here, we describe performance characteristics of monkeypox virus (MPXV)-specific and pan-orthopoxvirus qPCR assays for clinical use.

Methods: We validated probe-based qPCR assays targeting MPXV-specific loci F3L and G2R (genes MPXVgp052/OPG065 and MPXVgp002 and gp190/OPG002, respectively) and a pan-orthopoxvirus assay targeting the E9L locus (MPXVgp057/OPG071).

The world needs better male contraceptives: What is taking so long?

Forty percent of US pregnancies are unintended despite currently available contraceptives. A substantial number of men use the currently available methods of male contraception, condoms and vasectomy, and a large majority would be interested in novel forms of male contraception if available. Research into male contraception has been ongoing for more than 50 years, with hormonal contraceptives nearing clinical utility and non-hormonal methods hopefully becoming available, albeit with a longer time frame.

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety.

Background: Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT).

Aim: To determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning.

Methods: Hypogonadal men, between 18 and 75 years old, (mean age 56.

Dimethandrolone, a Potential Male Contraceptive Pill, is Primarily Metabolized by the Highly Polymorphic UDP-Glucuronosyltransferase 2B17 Enzyme in Human Intestine and Liver.

Dimethandrolone undecanoate (DMAU), an oral investigational male hormonal contraceptive, is a prodrug that is rapidly converted to its active metabolite, dimethandrolone (DMA). Poor and variable oral bioavailability of DMA after DMAU dosing is a critical challenge to develop it as an oral drug. The objective of our study was to elucidate the mechanisms of variable pharmacokinetics of DMA.

Can analysis of serum androgens aid in the diagnosis of polycystic ovary syndrome (PCOS) in adolescents?

Introduction: Polycystic ovary syndrome (PCOS) is a female metabolic disorder that is characterized by ovulatory dysfunction, elevated serum androgen concentrations, and polycystic ovarian morphology (PCOM). However, diagnosis of PCOS in adolescents is challenging.

Areas Covered: The mechanisms of PCOS pathophysiology are discussed that include: i) dysregulation of the levels of steroidal enzymes ii) abnormalities in the secretion of gonadotropin releasing hormone, luteinizing hormone, and follicle stimulating hormone , and iii) abnormalities in ovarian Thecal and Granulosa cell function.

Isotretinoin and its Metabolites Alter mRNA of Multiple Enzyme and Transporter Genes In Vitro, but Downregulation of Organic Anion Transporting Polypeptide Does Not Translate to the Clinic.

Isotretinoin [13--retinoic acid (13RA)] is widely used for the treatment of neuroblastoma and acne. It acts via regulating gene transcription through binding to retinoic acid receptors. Yet, the potential for isotretinoin to cause transcriptionally mediated drug-drug interactions (DDIs) has not been fully explored.

In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial.

Background: Loss of mitochondrial function contributes to fatigue, exercise intolerance and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial.

Methods: Non-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling (ATP supply per O2 uptake; P/O) at rest.

Acceptability of the oral hormonal male contraceptive prototype, 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), in a 28-day placebo-controlled trial.

Objective: To determine men's satisfaction with and the potential acceptability of 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) when used for 28 days as an experimental, once-daily, oral hormonal male contraceptive (HMC).

Study Design: We surveyed participants from a double-blind, randomized, placebo-controlled, phase 1 clinical trial, examining their experience with and willingness to use daily oral 11β-MNTDC for male contraception.

Results: Of 42 trial participants, 40 (30 11β-MNTDC, 10 placebo) completed baseline and end-of-treatment surveys.

Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

Background: Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility.

Emerging approaches to male contraception.

Despite significant interests in contraception by men, effective methods of male contraception are limited to vasectomy and condoms. Recently, there have been several promising advances in male contraceptive research. This review will update readers on recent research in both hormonal and nonhormonal approaches to male contraception.