Nestorone MDTS (elcometrine transdermal spray) / Population Council - LARVOL DELTA

Study of Efficacy, Cycle Control, and Safety of a NES-E2 Contraceptive Vaginal Ring (clinicaltrials.gov) - P2 | N=385 | Completed | Sponsor: Premier Research | Unknown status ➔ Completed

Trial completion

Male Hormonal Contraception-Current Stage of Knowledge. (PubMed, J Clin Med) - "Among the investigated agents, oral DMAU, 11β-MNTDC, and the Nestorone-testosterone gel appear to be the most promising candidates for male hormonal contraception due to their high efficacy, user-friendly administration, and favorable safety profiles. However, further large-scale clinical trials are necessary to confirm their long-term effects on human health and fertility, ensuring their viability as future contraceptive options."

Journal • Review • Long-acting Reversible Contraceptives

Effects of nestorone, a progesterone receptor agonist, on neonatal hypoxic-ischemic brain injury and reproductive functions in male and female rats. (PubMed, Neuropharmacology) - "These results suggest that nestorone exerts persistent neuroprotective effects against neonatal HI brain injury without serious adverse effects on reproductive functions in male and female rats. Therefore, nestorone is a promising potent and safe therapeutic agent in newborn infants with HIE of both sexes."

Journal • Preclinical • Cardiovascular • CNS Disorders • Vascular Neurology

Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception (clinicaltrials.gov) - P2 | N=420 | Completed | Sponsor: Health Decisions | Active, not recruiting ➔ Completed | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion • Trial primary completion date

Development of a transdermal gel for reversible male contraception. (PubMed, Contraception) - "Using the skin to deliver steroids in the systemic circulation is a well-accepted concept both for treatment of hypogonadism and contraception. A transdermal gel delivering Nestorone® (segesterone acetate) and testosterone is under development and is leading the way in advancing novel, self-delivered methods of male hormonal contraception."

Journal • Review • Endocrine Disorders

Anti-inflammatory effect of nestorone in a lipopolysaccharide-induced acute lung injury model through regulation of the TLR-4/Myd88/NF-κB signaling pathway. (PubMed, Inflammopharmacology) - "Progesterone plays a crucial and indispensable role in regulating immunity and attenuating inflammation...Interestingly, our findings indicate that NES at a dosage of 1 mg/kg (91.67%) was more effective than at dosages of 0.1 mg/kg (70.83%) or 10 mg/kg (87.50%), as well as more effective than dexamethasone (DEX, 5 mg/kg, 83.34%), in extending survival in mice subjected to lethal LPS-induced injury...Our study indicates that concentration is a critical determinant of the anti-inflammatory efficacy of NES. Consequently, NES emerges as a potentially promising therapeutic agent for the treatment of pulmonary inflammatory conditions through the modulation of TLR-4 signaling pathways."

Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • MYD88 • TLR4

Progesterone Receptor Agonist, Nestorone, Exerts Long-Term Neuroprotective Effects Against Permanent Focal Cerebral Ischemia in Adult and Aged Male Rats. (PubMed, Transl Stroke Res) - "These results suggested that nestorone exerts long-term neuroprotective effects against permanent focal cerebral ischemia in adult and aged male rats. Nestorone is thus a promising agent for post-stroke treatment owing to its wide age-independent therapeutic time window (18 h after symptom onset), which is longer than that of tPA therapy."

Journal • Preclinical • Cardiovascular

Testosterone and male contraception. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative."

Journal

Time to Sperm Suppression With Daily Transdermal Use of Nestorone and Testosterone Combination Gel for Male Contraception Is Faster Than Expected (ENDO 2024) - "More than 80% of participants using this novel male hormonal contraceptive gel formulation containing Nestorone 8 mg and Testosterone 74 mg showed suppressed sperm output within 12 weeks, a rate that appears to be faster than prior studies with other hormonal regimens. In view of this timeline based on the available data, more complete early assessment at weeks 4, 5, and 6 may have revealed a faster average time to suppression. A more rapid time to suppression may increase the attractiveness and acceptability to potential users.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation."

Development of new hormonal male contraception for the couple. (PubMed, Andrology) - "There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice."

Journal • Review

Male contraception: scientific progress and pending questions, a literature review (ESCRH 2024) - "Regarding methods whose biggest limitation is the route of application, two articles elucidated on transdermal HMC based on testosterone and nestorone gels, showing that washing on site limits the absorption of nestorone, even after a few hours of application... Recent studies reflect promising advancements in male contraception using various hormonal methods. Despite their advantages and disadvantages, these methods effectively suppress sperm production. However, concerns over adverse effects and acceptance persist."

Review • Acne Vulgaris • CNS Disorders • Long-acting Reversible Contraceptives • Mood Disorders • Psychiatry

Update on Transdermal NES/T Gel for Male Contraception (ESCRH 2024) - "The most advanced method in development is a transdermal gel delivering a progestin (Nestorone®) and testosterone to suppress the production of sperm...This hormonal male contraceptive gel is fully reversible, and results so far are very promising. Research must continue to develop effective, reversible options for men, to allow shared responsibility in the couple's fertility regulation and to curb maternal mortality."

Long-acting Reversible Contraceptives

Nestorone (segesterone acetate) effects on neuroregeneration. (PubMed, Front Neuroendocrinol) - "Nestorone® (segesterone acetate) is a progestin with a chemical structure closely related to progesterone with high affinity and selectivity for the progesterone receptor without significant interaction with other steroid receptors. Nestorone was found to display neuroprotective and neuroregenerative activity in animal models of various central nervous system diseases, including multiple sclerosis, stroke, and amyotrophic lateral sclerosis. Reviewed herein are neuroprotective and myelin- regenerating properties of Nestorone in various animal models and its translational potential as a therapeutic agent for debilitating neurological diseases for which limited therapeutic options are available (Table 1)."

Journal • Review • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Multiple Sclerosis • PGR

Risk Factors for and Outcomes of Ring Expulsions with a One Year Contraceptive Vaginal System. (PubMed, Am J Obstet Gynecol) - "Expulsions were infrequent overall, decreased with subsequent cycles of use and were not associated with BMI or parity. Early discontinuation of product use was higher among participants who experienced an expulsion during Cycle 1. While it is unclear whether pregnancy risk is associated with expulsions, early recognition of expulsions among users may identify those at higher risk for discontinuation and may highlight, where enhanced anticipatory counselling and guidance may be advantageous."

Journal

Male contraception: narrative review of ongoing research. (PubMed, Basic Clin Androl) - "There exist several hurdles to novel male contraception. Therapeutic development takes decades of time, meticulous work, and financial investment, but with so many strong candidates it is our hope that there will soon be several safe, effective, and reversible contraceptive options available to male patients."

Journal • Review

Clinical Approaches to Nestorone Subdermal Implant Therapy in Women's Health. (PubMed, Biomedicines) - "However, the absence of a standardized dose and the long-term safety of SA implant therapy in women is still controversial. Here, we present the possible indications, doses, limitations, and side effects of SA implant therapy."

Journal • Review • Endometriosis • Gynecology • Polycystic Ovary Syndrome • Women's Health

Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception (clinicaltrials.gov) - P2 | N=420 | Active, not recruiting | Sponsor: Health Decisions | Trial completion date: Dec 2024 ➔ Jul 2024

Trial completion date

Design of an International Male Contraceptive Efficacy Trial Using a Self-Administered Daily Topical Gel Containing Testosterone and Nestorone™ (ENDO 2023) - P2 | "We present the design of the first study to examine contraceptive efficacy, side effect profile and acceptability of a self-administered, reversible, male hormonal contraceptive product.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference."

Clinical • Endocrine Disorders

Design of an International Male Contraceptive Efficacy Trial Using a Self-Administered Daily Transdermal Gel Containing Testosterone and Segesterone Acetate (Nestorone®). (PubMed, Contraception) - "This manuscript outlines the study design and analysis plan for an ongoing large international trial of a novel transdermal hormone gel for male contraception. Successful completion of this and future studies of this formulation may lead to the approval of a male contraceptive."

Journal • Endocrine Disorders

Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception (clinicaltrials.gov) - P2 | N=420 | Active, not recruiting | Sponsor: Health Decisions | Recruiting ➔ Active, not recruiting

Enrollment closed

DESIGN OF AN INTERNATIONAL MALE CONTRACEPTIVE EFFICACY TRIAL USING A SELF-ADMINISTERED DAILY TRANSDERMAL GEL CONTAINING TESTOSTERONE AND NESTORONE™. (WSMRF 2023) - No abstract available

Clinical

Male Contraception Development: Monitoring Effective Spermatogenesis Suppression Utilizing a User-Controlled Sperm Concentration Test Compared with Standard Semen Analysis. (PubMed, Fertil Steril) - "Participants undergoing spermatogenesis suppression in a hormonal male contraceptive trial performed user-controlled test to determine whether their semen sperm concentration was ≤ or >0.2 million sperm/ml. Compared to standard semen analyses, participants correctly identified 100% of samples with sperm counts >0.2 million/ml as positive (Sensitivity 100%). A positive result when the couple is using a male contraceptive method triggers the need for semen analysis by a laboratory while the couple uses another method of contraception. Participants correctly diagnosed samples ≤0.2 million sperm/ml as negative in 99% of samples (Specificity 99%). A negative result indicates a sperm concentration ≤0.2 million/ml, well below the threshold of ≤1 million/ml offering contraceptive efficacy demonstrated by prior studies. At-home sperm concentration test would minimize the need for users to return to the clinic to monitor suppression of spermatogenesis, decreasing cost and..."

Journal

Short-acting but not a pill: what to expect? (ESCRH 2022) - "Several male hormonal methods are currently under development; the most advanced being a Nestorone/testosterone transdermal gel applied daily, able to suppress spermatogenesis while maintaining sexual function...Improved contraceptive technologies can offer more choices to couples and help meet their disparate needs that emerge at different times of their reproductive lives. More investment in contraceptive research and development can help in that direction."

Risk factors for and outcomes of expulsions with a one year contraceptive vaginal system (ESCRH 2022) - "Objectives: Annovera®, a newly FDA-approved Nestorone®/ethinyl estradiol contraceptive vaginal system (CVS) is inserted and removed under a woman’s control for a 21 day in/7 day out regimen for up to 13 cycles of use... Expulsions were infrequent overall, decreased with subsequent cycles of use and was not associated with BMI or parity. Pregnancy risk appeared higher and early discontinuation of product use was higher among women who did experience an expulsion during cycle 1. Early recognition of expulsions among users may identify those at higher risk for discontinuation and pregnancy, where enhanced counselling may be advantageous."

Clinical

Moving forward with the hormonal approach to male contraception (ESCRH 2022) - "Currently, these novel steroids hold promise as both a “male pill” and long-acting injections. A contraceptive efficacy trial of Nestorone®/testosterone gel is ongoing."

Long-acting Reversible Contraceptives