Evaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive.

Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.

Identification of the Biotransformation Pathways of a Potential Oral Male Contraceptive, 11β-Methyl-19-Nortestosterone (11β-MNT) and Its Prodrugs: An In Vitro Study Highlights the Contribution of Polymorphic Intestinal UGT2B17.

11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models.

Contraceptive efficacy: Determining the threshold for effective suppression based on sperm concentration, motility, and morphology.

Introdction: Human spermatogenesis is a complex process that transforms spermatogonial stem cells through mitosis and meiosis to spermatozoa. Testosterone is the key regulator of the terminal stages of meiosis, adherence of spermatids to Sertoli cells, and spermiation. Follicle-stimulating hormone (FSH) may be required for early spermatogenesis and is important for maintaining normal spermatogenesis in men.

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

Background: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy.

Methods: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use.

Development of new hormonal male contraception for the couple.

Background: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning.

Objectives: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel.

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial.

Objectives: To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones.

Study Design: We used standard chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg reporting no recent use of hormonal contraception.

Results: We enrolled 532 and obtained a valid baseline blood sample from 520 women.

Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel.

Objectives: To compare the efficacy of emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing ≥80 kg.

Study Design: We enrolled reproductive-aged healthy women in a multicenter, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

Objective: To evaluate menstrual cup use and intrauterine device (IUD) expulsion.

Study Design: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD.

Novel progestogenic androgens for male contraception: design, synthesis, and activity of C7 α-substituted testosterone†.

Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs.

Participant experiences with a multipurpose vaginal ring for HIV and pregnancy prevention during a phase 1 clinical trial: learning from users to improve acceptability.

Introduction: With high concurrent global rates of HIV incidence and unintended pregnancy, there is a need to provide options beyond condoms to enable users to simultaneously prevent HIV acquisition and pregnancy. Multiple vaginal rings are in development as "MPTs" (multipurpose prevention technologies) as they are shown to provide several co-occurring benefits such as discretion, convenience, reversibility and user control.

Methods: In this Phase 1 trial of a 3-month MPT ring in the U.

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.

Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis.

Objective: To determine whether a user-controlled sperm concentration test compared with standard semen analysis can effectively monitor spermatogenesis suppression for male contraception.

Design: Single center, prospective sub study of the ongoing clinical trial: "Study of daily application of Nestorone and testosterone combination gel for male contraception."

Setting: Research institute at an academic medical center.

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.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users.

Hormonal Male Contraception: Getting to Market.

Rates of unplanned pregnancies are high and stagnant globally, burdening women, families and the environment. Local limitations placed upon contraceptive access and abortion services exacerbate global disparities for women. Despite survey data suggesting men and their partners are eager for expanded male contraceptive options, efforts to develop such agents have been stymied by a paucity of monetary investment.

Global research and learning agenda for building evidence on contraceptive-induced menstrual changes for research, product development, policies, and programs.

: Contraceptive-induced menstrual changes (CIMCs) can affect family planning (FP) users' lives in both positive and negative ways, resulting in both opportunities and consequences. Despite this, and despite the important links between FP and menstrual health (MH), neither field adequately addresses CIMCs, including in research, product development, policies, and programs globally. : In November 2020, a convening of both MH and FP experts reviewed the existing evidence on CIMCs and identified significant gaps in key areas.

Male contraception is coming: Who do men want to prescribe their birth control?

Objective: To assess men's preferences for healthcare provider from whom they would obtain hormonal male contraceptive (HMC) methods.

Study Design: We asked participants from 3 clinical trials of investigational HMC methods-an oral pill (11β-Methyl-19-nortestosterone-17β-dodecylcarbonate, 11β-MNTDC), intramuscular or subcutaneous injection (Dimethandrolone undecanoate), and transdermal gel (Nestorone and testosterone)-to rank their top 3 preferred HMC providers from a list including: men's health doctor (urologist/andrologist), hormonal doctor (endocrinologist), reproductive health doctor (OB/GYN), family planning clinician (community health worker, midwife, nurse practitioner), regular doctor (family medicine/internal medicine), and community pharmacist. We examined preferences based on their rankings and conducted bivariate analyses.

Evaluation of ovulation and safety outcomes in a multi-center randomized trial of three 84 day ulipristal acetate regimens.

Objectives: To describe ovulation inhibition and safety of daily oral ulipristal acetate (UPA) over 84 days.

Study Design: This multi-center phase 1 and/or 2 trial randomized participants to use oral ulipristal 10 mg or 5 mg daily or a 3 cycle regimen of 5 mg for 24 days followed by four placebo days. We stratified randomization by body mass index (BMI) <32 or 32-40 kg/m.

Contraceptive and Infertility Target DataBase: a contraceptive drug development tool for targeting and analysis of human reproductive specific tissues†.

The long and challenging drug development process begins with discovery biology for the selection of an appropriate target for a specific indication. Target is a broad term that can be applied to a range of biological entities such as proteins, genes, and ribonucleic acids (RNAs). Although there are numerous databases available for mining biological entities, publicly available searchable, downloadable databases to aid in target selection for a specific disease or indication (e.

Pharmacodynamics and pharmacokinetics of a copper intrauterine contraceptive system releasing ulipristal acetate: A randomized proof-of-concept study.

Objectives: To assess pharmacodynamic and pharmacokinetic outcomes of a novel copper (Cu) intrauterine system (IUS) releasing ulipristal acetate (UPA) in healthy women.

Study Design: In this single-blinded, randomized proof-of-concept study, ovulatory women received one of three Cu-IUSs releasing low-dose UPA (5, 20 or 40 µg/d) for 12 weeks. The study included a baseline cycle, three 4-week treatment-cycles and 2 recovery cycles.

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.

Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men.

Background: Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men.

Objective: Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens.

Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.

Background: The advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male contraception has been dormant since the 1990s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development.