New Horizons in Male Contraception: Clinical, Cultural and Technological Innovation Aspects

Abstract

Background/Objectives: The main contraceptive options for men are condoms, vasectomy and coitus interruptus. Clinical and preclinical trials are being conducted to develop a new male contraceptive (NMC), which can be either hormonal or non-hormonal. A patent landscape and literature review of clinical studies from the last 10 years were carried out to discuss clinical perspectives and sociocultural aspects related to the use of NMC. Methods: An integrative review of clinical aspects was conducted using eleven clinical trials, and a discussion of sociocultural aspects was conducted using thirteen articles. Results: Studies of non-hormonal contraceptives, particularly vaso-occlusive methods, are in more advanced clinical phases, demonstrating contraceptive potential and reversibility. In addition to clinical trials, efforts to develop NMC include addressing gender disparities and understanding masculinity. Alternative technologies and methods for contraception were identified as key to the development of NMC. Despite clinical and technological advances, there is a need to expand clinical studies on male contraceptives, involving larger samples, long-term follow-ups, and reversibility tests. There is a global social need that both men and women should have a wide variety of contraceptive options. Conclusions: This review emphasizes the importance of exploring new technologies for male contraceptives to expand options while optimizing the satisfaction and safety of these contraceptive options for the population.

1. Introduction

Worldwide, condoms, vasectomies and coitus interruptus (as temporary and ongoing methods) are the main contraceptive options for men. The use of condoms is a very popular method of contraception, especially among those who may have infrequent sexual intercourse, such as young people. Its reported perfect use rate is two possible pregnancies in the first year of use, provided it is used correctly and for every sexual intercourse. Condoms are effective and are seen as a method of preventing pregnancy and sexually transmitted infections [1,2]. Compared to tubal ligation, vasectomy is a shorter and more effective procedure performed on men with the possibility of reversal and with efficacy rates reported as high as 50–80%. However, it is still a method that is not widely accessible globally. The low use of vasectomy may be related to misconceptions about the procedure and its effects [1,3]. Coitus interruptus or withdrawal remains a widely used traditional contraceptive method globally, with 53 million users representing 5.5% of all contraceptive users in 2020 [4]. The World Health Organization cites a 4% failure rate with perfect use and 22% with typical use [5]. This method is considered a “false” or ineffective method [6], however and, in typical use, has a failure rate better than some female barrier methods [4]. This is a method that requires no interaction with the medical community, and something people can do on their own. Clinical and preclinical studies using hormonal and non-hormonal contraceptives are being conducted to develop new male contraceptives (NMC). However, gaps remain in this area, and the choice of contraceptive method depends on the individuals involved as well as their sociocultural contexts and clinical factors.

Access to a wide range of effective contraceptive methods tested in clinical trials is also essential for fertility control and achieving good reproductive health. Although male contraceptives have been in development since the 1970s, new approaches to contraception have only been approved and expanded for women [7,8,9]. Biological factors, such as the difficulty of targeting spermatogenesis without disrupting male reproductive organs; the challenge of achieving consistent and rapid suppression of sperm production; the need to ensure long-term reversibility without causing irreversible infertility or significant side effects; and, the complexity of the blood-testis barrier (BTB) prevents many drug candidates from effectively reaching the seminiferous epithelium to exert their effects, are the main barriers to the use and commercialization of NMC [10]. From a social perspective, contraceptives have a greater impact on women due to the physiological and social challenges associated with unplanned pregnancies, such as social adversities, stress, and depression [8]. Furthermore, the male public’s view of reproductive health is heavily influenced by social constructions of masculinity, or “hegemonic masculinity.” This concept refers to a set of beliefs, expectations, actions, and practices that are considered essential for men in certain cultures, such as self-sufficiency, mastery, self-perceived invulnerability, and emotional control. These pre-established patterns contribute to the discrimination, marginalization, stress, and health problems experienced by this group due to their lower likelihood of seeking help [11,12].

According to the Brazilian Ministry of Health, a total of 155,314 vasectomies and 157,938 tubal ligations were performed in the last 5 years, generating a cost of over 10 million dollars [13]. Given the prospect of using these new contraceptive methods, the role of the multidisciplinary health team is relevant [14]. The challenges involved in NMC require these professionals to have knowledge on topics such as gender equality and equity, masculinity, religion, identity, and gender barriers. Therefore, including this knowledge in the approach to men is fundamental for improving clinical approaches and providing humanized care. Thus, the multidisciplinary health team to develop skill in development, offering, counseling men and motivating them to use those methods.

Hormonal contraception involves the use of exogenous substances that act on the hypothalamic-pituitary-gonadal (HPG) axis, which is the naturally occurring hormonal feedback cycle, to suppress spermatogenesis. New substances in this category include Gonadotropin Releasing Hormone (GnRH) antagonists, dimethandrolone undecanoate (DMU), 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC), and certain progestogens and testosterone. Non-hormonal contraceptives target proteins that affect sperm production or function, and they also use vaso-occlusive methods to block the passage of sperm. One example is “Reversible Inhibition of Sperm under Guidance (RISUG)” [9,15]. Therefore, this category has a large and growing number of potential targets. Additionally, prospecting alternative technologies and methods for contraception is essential for developing new drugs. Like the female hormonal contraceptives, NMC are being tested through different routes of administration: oral, parenteral (intramuscular), implants, and transdermal gels [16].

The literature provided information on the clinical and sociocultural aspects that can help multidisciplinary teams guide and advise male patients on contraceptive use [17]. However, a more comprehensive analysis is still necessary, particularly regarding gender-specific attitudes toward contraceptive responsibility. This study aimed to conduct technological prospecting of patents and articles published in scientific literature within the last 10 years. This article will discuss clinical perspectives and sociocultural aspects related to the use of NMC.

2. Materials and Methods

An integrative review was conducted to examine the current publications and future prospects of NMC usage. The following databases were used: PubMed, Scientific Electronic Library Online (SciELO), Virtual Health Library (VHL), and the Journals Portal of the Coordination for the Improvement of Higher Education Personnel (CAPES) in Brazil. The keywords used for the searches were: “male” AND “contraceptive” AND “clinical”, for the searches related to clinical aspects; and “reproductive health” AND “(masculinity OR gender equality)” AND “male contraceptive”, for searches related to sociocultural aspects. The review included literature reviews and clinical studies limited to the last 10 years that focused on the clinical and sociocultural aspects of NMC. The inclusion criteria were texts that were fully and openly accessible to allow transparency and reproducibility. Only studies that addressed the eligible population (age and physiological condition favorable for reproduction) for contraceptive use (hormonal and non-hormonal) were included. For the clinical approach, only clinical trials and case studies were included, and for the sociocultural approach, only qualitative epidemiological research was included. Articles that were duplicates between or within databases, as well as studies that did not address the issues of this review (e.g., political and regulatory positions studies and other methodological types), were excluded.

The patent search was conducted in Espacenet, the database maintained by the European Patent Office (EPO), focusing on male contraception technologies identified during the prior literature review. Searches were performed in Espacenet using the terms dimethandrolone undecanoate, 11β-methyl-19-nortestosterone, and reversible inhibition of sperm under guidance (RISUG), including orthographic and chemical-name variations (e.g., “11 beta methyl 19-nortestosterone,” hyphenation and spelling variants for RISUG) to maximize retrieval. Only patents available in English or Spanish were included to ensure accuracy and facilitate data extraction. No geographic restrictions were applied, and all jurisdictions indexed by Espacenet were considered eligible. The publication date range was limited to documents published between 1 July and 31 October 2024. Both patent applications and, when available, granted patents mentioning the target terms in the title or abstract and whose technical content addressed male contraception (mechanism of action, dosage form, route of administration, or contraceptive claims) were included.

Records were consolidated at the patent family level to remove duplicates and avoid double counting across jurisdictions. Screening was performed in two sequential phases. First, title screening excluded clearly out-of-scope items (e.g., documents using the search terms in unrelated contexts), resulting in the exclusion of 200 of the initially retrieved 359 records. The remaining records underwent abstract and, when necessary, full-text specification screening to clarify scope and claims. Documents were excluded at this stage if they were unrelated to male contraception, merely cited the search terms without substantive relevance, or lacked sufficient bibliographic or technical information for data extraction.

3. Results and Discussion

3.1. Study Selection and Clinical Aspects of the Articles Analyzed

Figure 1 shows the data selection steps. Eleven studies involving nine substances and/or devices with contraceptive potential were analyzed. Eight of these studies were with potential hormonal contraceptives, three were with non-hormonal contraceptives (two of which were in a more advanced clinical phase, Phase III), and four were for the discussion regarding sociocultural aspects. Six of the eleven clinical trials presented safety, efficacy, and reversibility tests of these contraceptives using similar methodological approaches. Two studies examined only 11β-MNTDC (33.33%), three examined DMU (50%), and one examined both substances (16.67%) (

Table 1. Study variables related to the clinical aspects of the articles analyzed.

Authors/Year	Substance(s)	Clinical Trials Stage	Dosage	Laboratory Parameters	Undesirable Effects	Drug Interactions
Nguyen et al. (2021) [18]	11β-MNTDC	Phase Ib (n = 40)	200 mg (group 1) and 400 mg (group 2) in the morning, orally, 30 min after a high-fat meal, for 28 days.	-	Decreased libido, mood swings, weight gain and fatigue.	Fat intake increases drug bioavailability
Wu et al. (2019) [19]	11β-MNTDC	Preclinical phase and Phase I (n = 12)	100; 200; 400; or 800 mg, orally, on an empty stomach for at least 8 h and, on another occasion, after a meal rich in fat (>50%). Single dose.	No statistically significant suppression of FSH.	Weight gain, decreased hematocrit, without serious adverse effects	Fatty foods increase drug bioavailability
Yuen et al. (2021) [20]	11β-MNTDC and DMU	(n = 78) [38 DMU; 40 11β-MNTDC]	200 and 400 mg once a day, orally, for 28 days, 30 min after a high-fat meal	Adiponectin: DMU (placebo, 1.4 μg/mL; active, −1.7 μg/mL; p < 0.01)/11β-MNTDC (placebo, −1.5 μg/mL; active, −0.4 μg/mL) HDL-C: DMU (200 mg–13 mg/dL and 400 mg–11 mg/dL)/11β-MNTDC (200 mg–11 mg/dL and 400 mg–16 mg/dL) Hematocrit: variations of 1% for 11β-MNTDC 200 mg and 400 mg and 2% for DMU 400 mg	Significant increase in weight and hematocrit; decrease in HDL-C not related to dose	-
Ayoub et al. (2017) [21]	DMU	Phase Ib (n = 44)	100; 200 and 400 mg formulated in castor oil, SEDDS and powder (in capsule). After a fatty meal. Single dose.	Ranges for the two doses (200 and 400 mg): LH: 1.5–2 UI/L FSH: 2–2.5 UI/L T: 200–250 ng/dL Values with 400 mg were lower.	-	Fat administration increases drug absorption and serum concentration.
Thirumalai et al. (2019) [22]	DMAU	Phase Ib (n = 100)	Group C: 100, 200 or 400 mg of 70% castor oil/30% benzyl benzoate. Group P: 200 or 400 mg of powder in capsule form, daily, for 28 days. After breakfast containing 25 to 30 g of fat.	Group C100: 54% LH and FSH < 1 IU/L 46.2% serum T < 50 ng/dL Group C200: 64% LH and FSH < 1 IU/L 64.3% serum T < 50 ng/dL Group C400: 92% LH and FSH < 1 IU/L 92.3% serum T < 50 ng/dL Group P200: 69% LH and FSH < 1 IU/L 76.9% serum T < 50 ng/dL Group P400: 100% LH and FSH < 1 IU/L 100% serum T < 50 ng/dL There was no significant decrease in sperm levels	Headache (13 patients, “mild”); decreased libido (9 patients, “moderate”); erectile dysfunction (3 patients, “mild”); acne (8 patients, “moderate”); Weight gain, elevated hematocrit levels, and decreased HDL-C	Fat administration increases drug absorption
Surampudi et al. (2014) [23]	DMU	Phase I (n = 12)	25; 50; 100; 200; 400 and 800 mg fasting; 200, 400 and 800 mg after high-fat diet (>50%). Single dose.	LH (200 mg): 3.5–4.0 IU/L (fasting) 2.5–3.0 IU/L (post meal) LH (400 and 800 mg): 3.0–3.5 IU/L (fasting) ~2 IU/L (post meal) FSH (200 mg): 3.5–4.0 IU/L (fasting) 3.0–3.5 IU/L (post meal) FSH (400 and 800 mg): ~3.0 (fasting) 3.5–4.0 IU/L (800 mg fasting) 2.5–3.0 IU/L (post meal) T (200 mg): 15–18 nmol/L (fasting) 15–18 nmol/L (post meal) T (400 mg and 800 mg): 15–18 nmol/L (fasting) ~10 mmol/L (after meal)	“Mild” acne	Fat intake increases drug bioavailability
Anwalt et al. (2019) [24]	Segesterone acetate (Nesterone) and testosterone.	Phase 1 (n = 44)	Nes/T Group: Nes (8.3 mg) and 1.62% T (62.5 mg) in 5 mL of gel. T Group: 1.62% T (AndroGel® III T 62.7 mg) in 4.4 mL of gel. Daily application of the gel in the abdominal region for 28 days.	Nes/T Group: (21–28 days) LH and FSH ≤ 1 UI/L. (Day 28) No significant differences in free T value. (Day 28) Sperm concentration decreased significantly (40 ± 43 million/mL). T Group: LH and FSH values ≤ 1 UI/L were not reached. (Day 28) Free T value was significantly higher. (Day 28) Sperm concentration was unchanged (85 ± 72 million/mL)	Rash (dry and scaly) at the application site (1 patient), sunburn at the application site (2 patients), and decreased libido (1 patient)	-
Zitzmann et al. (2017) [25]	Cyproterone acetate (CPA), nesterone (NES), norethisterone acetate (NETA), levonorgestrel (LNG) and testosterone.	Phase I (n = 56)	1st phase (2 weeks, 8 groups): Cyproterone acetate (CPA)—10 mg/day or 20 mg/day; Norethisterone acetate (NETA)—5 mg/day or 10 mg/day; Levonorgestrel (LNG)—120 µg/day or 240 µg/day and Nesterone (transdermal)—1 g of gel per day, 2 mg/g or 3 mg/g gel. 2nd phase (4 weeks, 8 groups): 50 mg of testosterone gel (10 mg/g) in combination with each of the progestins.	FSH: CPA 10 mg/day and 20 mg/day: >0.5 IU/L CPA combined: <0.5 IU/L NES 2 mg/g: >0.5 IU/L NES 3 mg/g: >0.5 IU/L NES combined: >0.5 IU/L (2 mg/g); =0.5 IU/L (3 mg/g) NETA 10 mg/day and 20 mg/day: >0.5 IU/L NETA combined: <0.5 IU/L LNG 10 mg/day and 20 mg/day: >0.5 IU/L LNG combined: <0.5 IU/L LH: CPA 10 mg/day and 20 mg/day: >0.5 IU/L CPA combined: <0.5 IU/L NES 2 mg/g: >0.5 IU/L NES 3 mg/g: >0.5 IU/L NES combined: >0.5 IU/L (2 mg/g); <0.5 IU/L (3 mg/g). NETA 10 mg/day and 20 mg/day: >0.5 IU/L NETA combined: <0.5 IU/L. LNG 10 mg/day and 20 mg/day: >0.5 IU/L LNG combined: <0.5 IU/L	NETA (with T): night sweats (possible), axillary eczema (possible), laryngitis (possible). NES (with T): increased aggression, increased anger, decreased libido (all possible).	-
Bhat et al. (2019) [26]	Silodosin	Phase I (n = 63)	8 mg, 3 h before masturbation or sexual intercourse.	Number of sperm (millions/ejaculate): 1–7th day Group A (silodosin): 0 Group B (placebo): 78.41 ± 1.95 8th–14th Group A (placebo): 73.06 ± 3.13 Group B (silodosin): 0 million/ejaculate 15th–30th Group A (placebo): 75.42 ± 1.37 Group B (placebo): 77.14 ± 1.78	Nasal congestion: >35% Vertigo: >16% Weakness: >15% Scarce ejaculation: >88%	-
Lu et al. (2014) [27]	Non-obstructive polyurethane and barium sulfate intravascular device (IVD-A and IVD-B).	Phase III (n = 1459)	3 groups: IVD-A, IVD-B and no-scalpel vasectomy (VSB). Followed from the 3rd to the 6th month postoperatively and 12 months postoperatively.	3–6 months Sperm concentration = 0 mL−1 IVD-A: 60.22% IVD-B—56.54% VSB—86.50% Sperm without progressive motility IVD-A: 32.96% IVD-B: 35.20% VSB: 60.66% 12 months Sperm concentration = 0 mL−1 IVD-A: 79.96% IVD-B—84.15% VSB—95.98% Sperm without progressive motility IVD-A: 45.56% IVD-B: 50.70% VSB: 68.42%	Congestive epididymitis and granuloma. After 12 months: 0.89% for the IVD-B group and 1.70% for the VSB group. No serious adverse events were observed.	-
Sharma et al. (2019) [7]	Styrene maleic anhydride (SMA) copolymer in dimethyl sulfoxide (DMSO).	Phase III (n = 133)	60 mg of SMA in chemical complex with 120 μL of DMSO = 120 μL of RISUG.	Azoospermia in all individuals (133) in the period of 1–6 months. Azoospermia: 82.7% in 2 months 17.3% in 3–6 months	Diffuse edema of scrotal tissue and mild scrotal pain (disappeared within one month of use). Scrotal lump at the injection site (disappeared within six months).	-

The numbers of laboratory parameters in the study by Yuen et al. (2021) [20] are given in variations in the values of each test. CPA: Cyproterone acetate; DMU: Dimethandrolone undecanoate; FSH: follicle-stimulating hormone; HDL: high-density lipoprotein; IVD-A: Intravas A device; IVD-B: Intravas B device; 11β-MNTDC: oral 11β-methyl-19-nortestosterone; LH: luteinizing hormone; NHL: levonorgestrel; Nes: Nesterone; T: Testosterone; SEDDS: self-emulsifying drug delivery systems; PO: Oral route, NES: nestorone; NETA: norethisterone acetate; VSB: no-scalpel vasectomy.

).

3.2. Pharmacology and Clinical Approach of NMC: Hormonal Contraceptives

Oral hormonal contraceptives operate via a similar mechanism involving negative feedback from the hypothalamic–pituitary–gonadal axis (Figure 2).

DMU, an ester that converts to dimethandrolone (DMA), which in time suppresses LH and FSH secretion from the pituitary gland by acting on both androgen and progesterone receptors [23]. In studies of absorption, a dose-finding study compared bioavailability of DMU when it was given fasting versus when it was taken with a high fat diet (fats more than 50% of calories value of the meal). High fat diet was associated with nearly 80-fold higher levels of DMA than with fasting conditions [23]. Castor oil formulations of DMU in a self-emulsifying drug delivery system (SEDDs) improved DMU conversion to DMA compared to DMU in powder in capsules. This study also suggested that administering the contraceptive in oil would be advantageous for multiple-dose studies because it would allow for significantly lower serum levels of DMU [21]. The rapid and potent impact of DMU (administered once daily at doses of 0, 100, 200 or 400 mg) on suppressed gonadotropin secretion and endogenous testosterone production was evaluated after seven to ten days (with greater suppression observed at the 400 mg dose) [22].

Similar to DMU, the 11β-methyl-19-nortestosterone 11 (β-MNTDC) is an oral prodrug of a synthetic androgen with progestational activity. Its active metabolite, 11β-methyl-19-nortestosterone (11β-MNTE), has a high binding affinity to the androgen receptor, greater than that of testosterone. However, it has a lower binding affinity to the progesterone receptor than progesterone [20,28]. The literature presents comparative studies between DMU and 11β-MNTDC that evaluate their clinical effects and undesirable side effects (e.g., decreased libido, acne, and erectile dysfunction), and the acceptability in healthy men over 28 days. In these studies, the undesirable effects were not separated by group according to dose (200 or 400 mg), making it unclear whether the effects depend on the contraceptive dose. Other adverse effects may arise with prolonged use of 11β-MNTDC [18,22].

The oral administration of 11β-MNTDC was well tolerated by healthy men at single doses of up to 800 mg without any serious adverse effects. There was no suppression of FSH, and statistically significant suppression of LH was observed only in the 200 mg group [19]. These values differ greatly from those in previous studies involving DMU. The authors noted the reduced sample size (n = 12) and the lack of a dose–response relationship with a single 11β-MNTDC dose, which may be insufficient to suppress gonadotropins. Despite testosterone suppression, most individuals did not experience symptoms of acute androgen deficiency, such as hot flashes. This suggests that the androgenic effects of DMA at the studied doses may approach those of endogenous testosterone. Therefore, greater dose definition is needed for optimal DMU tolerability [22,29]. No studies proposing this dose refinement were found in searches of the scientific literature until the year 2024.

The metabolic and adverse effects of DMU and 11β-MNTDC in healthy men after 28 days of daily dosing [20]. Adiponectin, a hormone secreted by fat cells that improves insulin sensitivity, was evaluated because low levels of this hormone contribute to insulin resistance and the increased cardiovascular risk associated with obesity and metabolic syndrome [30,31]. In this clinical trial, there was a slight decrease in adiponectin levels, but no changes in insulin levels or insulin resistance. Due to the short duration of the study and the small number of participants (n = 40), further research is necessary to draw conclusions about the effects on adiponectin. Regarding weight gain, it is suggested that it may be secondary to an increase in muscle or fat mass or to sodium and water retention, and future studies are necessary to determine the etiology [20]. Regarding variations in HDL-C levels (desirable values > 40 mg/dL fasting and non-fasting), contraceptives can trigger secondary dyslipidemias, which can cause an increase in total cholesterol and triglycerides and a decrease in HDL-C [32]. Therefore, these individuals must be monitored in terms of cardiovascular risk stratification.

Nesterone (segesterone acetate), a progestin derived from 19-norprogesterone (a synthetic progesterone analog), has minimal androgenic, estrogenic, and glucocorticoid activity. It has minimal effects at therapeutic doses and is associated with fewer side effects than many other synthetic progestins [24]. Different doses of some progestogens (oral and transdermal) were compared with and without transdermal testosterone [25]. In terms of gonadotropin suppression, the most robust effect was observed with cyproterone acetate (CPA) in combination with testosterone gel. No dose-dependent suppression effect was observed between groups [25]. Therefore, lower progestogen doses could be used in the future, reducing the likelihood of undesirable effects.

The effects of Nestorone^® gel with testosterone (Nes-T) and testosterone alone (AndroGel^®) were compared for 28 days [24]. Serum gonadotropin concentrations were suppressed more significantly with the combined gel (less than 1 IU/L for two days after the last application in the Nes-T group). This suggests that missing a dose (or two) does not affect the contraceptive efficacy of the combined gel. Also, may indicate better adherence to and adaptation with the contraceptive in question compared to others, such as the combination of oral progestogens and testosterone gels [25]. However, it should be noted that poor absorption of steroid hormones can result from lack of adherence to the regimen, differences in the surface area of application, or removal of the gel soon after application (e.g., cleaning or washing the application site) [24]. There is extensive discussion about the characteristics of the formulation and mechanisms of action of this transdermal gel, which combines Nestorone and testosterone [24,33]. The transdermal gel that releases NES and T is considered the most advanced male contraceptive because the exogenous androgen replaces the testosterone that has been suppressed, thereby minimizing side effects for users. Reports confirm the product’s efficacy, safety, and high user acceptance. Thus, the NES/T gel is an innovative, user-controlled contraceptive method that can transform how couples decide to regulate their fertility [33]. Meanwhile, studies have found that transdermal transfer of testosterone from men (using this gel) to women can be prevented by washing or covering the application sites with clothing [20,34].

Male hormonal contraception works by inhibiting sperm production in the testicles. This process is controlled by FSH, which is produced by the anterior pituitary gland. The release of FSH depends on GnRH, which is secreted in pulses by the hypothalamus and acts on receptors in the gonadotropic cells of the pituitary gland. These cells produce both FSH and LH (luteinizing hormone), releasing them into the bloodstream. The major challenge in developing a male hormonal contraceptive is not suppressing FSH because this can be effectively achieved using androgens, progestins, or GnRH analogs. However, these compounds also reduce LH, which is responsible for testosterone production in men by Leydig cells in the testes and in women by theca cells in the ovaries [35].

DMU and Relugolix—a gonadotropin-releasing hormone (GnRH) receptor antagonist—have different yet complementary mechanisms of action for contraceptive and therapeutic treatments [36]. DMU has shown significantly increased bioavailability when administered on an empty stomach with a high-fat diet. It has the potential to suppress testosterone and other gonadotropins, favoring control of DMA concentration [36]. This is particularly noted when DMU is administered in oil formulations [21]. However, prolonged clinical trials have revealed adverse effects, such as decreased libido and erectile dysfunction. This highlights the need for further studies on tolerability and optimal dosage [22]. In contrast, Relugolix is notable for its rapid and potent inhibition of FSH and LH release, providing sustained suppression of testosterone levels, particularly in the treatment of advanced prostate cancer. Though they have different mechanisms of action, both treatments demonstrate the potential of hormonal antagonists and modulators in treating various clinical conditions. Therefore, there is an ongoing need to optimize dosages to minimize adverse effects and maximize therapeutic benefits [33].

3.3. Pharmacology and Clinical Approach of NMC: Non-Hormonal Contraceptives

Non-hormonal vaso-occlusive contraceptive methods, such as non-obstructive polyurethane and barium sulfate intravascular devices (IVD-A and IVD-B), as well as “reversible inhibition of sperm under guidance (RISUG)”, have a similar mechanism of action based on creating a temporary physical blockage in the lumen of the vas deferens. This blockage prevents the passage of sperm and alters the sperm acrosome membrane [9,10]. The mechanism of action of IVD-A, IVD-B, and RISUG involves blocking the release of sperm through the use of reversible physical barriers. RISUG consists of injecting a styrene maleic anhydride polymer mixed with a dimethyl sulfoxide solvent into the ducts deferens, which are responsible for transporting sperm from the epididymis. This polymer is understood to have the ability to damage sperm, rendering them ineffective [28,37].

Of the three studies on potential non-hormonal contraceptives, the oldest compares two groups: one that uses the IVD-A and IVD-B devices, and one that undergoes the no-scalpel vasectomy procedure [27]. Pregnancy rates in the IVD group were not higher than those in the vasectomy group. Contraceptive failures were explained in the groups as possible motile sperm in the epididymal fluid transported through the IVD. Alternatively, they could be due to the passage of motile sperm through the spaces between the device and the wall of the vas deferens due to the loose ligature and fixation. Adverse effects and long-term complications were significantly less common in the IVD group than in the vasectomy group [27].

The efficacy of RISUG as a non-hormonal contraceptive has been evaluated. Most individuals who received the full RISUG injection dose achieved oligospermia or azoospermia within two months (82.7%), while the remainder achieved azoospermia within six months [7]. These results were more favorable than those of the IVD-A and IVD-B devices [27]. However, the reversibility of RISUG has not been tested in humans, and successful reversal has only been observed in studies with rats, rabbits, and langur monkeys [7].

One of the arguments that distances pharmaceutical companies from new male contraceptives is the reversibility of the contraceptive method [38,39]. Previous results reported the efficacy, safety, and reversibility of IVD sterilization in rabbits compared to vasectomy. Reversal operations resulted in less trauma in the IVD group than in the vasectomy group, suggesting that this may be an undisclosed mechanism [27]. However, the reviewed studies had some methodological limitations, including small sample sizes and short durations. For instance, the silodosin study included fewer than 100 men, which made it difficult to calculate the contraceptive efficacy rate. Additionally, analyses of changes in spermatogenesis were hindered in DMAU studies due to their short duration since a normal spermatogenesis cycle takes 74 days. Therefore, despite advances, significant challenges remain in this field of research [40,41].

Silodosin acts to decrease semen volume during ejaculation (abnormal or retrograde ejaculation) by blocking α-1A adrenergic and P2X1 purine receptors [26]. The α-1A adrenergic receptors are located in the lower urinary tract and primarily regulate smooth muscle tone in the bladder neck, prostate, and prostatic urethra. Antagonizing this receptor can improve urinary symptoms by relaxing the lower urinary tract. The Food and Drug Administration (FDA) approved this drug in 2008 for the treatment of benign prostatic hyperplasia; however, it can cause azoospermia during ejaculation and is therefore being studied as a potential contraceptive agent [26,42]. The most common side effects of silodosin are retrograde ejaculation and anejaculation (reduced volume or absence of sperm). Because α-1A adrenergic receptors are primarily expressed in the bladder neck, ducts deferens, and seminal vesicles, silodosin’s high selectivity for this receptor subtype causes relaxation of the smooth muscle in the prostate, urethra, bladder neck, and ducts deferens. This may result in retrograde ejaculation [43]. The oral potential of silodosin (8 mg) was evaluated, achieving total and reversible azoospermia with a reduction in semen volume (less than 1 mL) after the first dose within a 30-day treatment period [26]. This reduction in ejaculate volume may influence volunteers’ perception of the change from drug to placebo, which is one limitation of the study.

3.4. Aspects Related to Technological Innovation of NMC from Patent Applications

After applying all inclusion and exclusion criteria, 32 patent documents met eligibility requirements and were included in the final analysis. For each included document, bibliographic and technical information was systematically extracted into a structured spreadsheet, recording at minimum: title, applicants/assignees, publication and priority numbers/dates, jurisdictions, International Patent Classification (IPC)/Cooperative Patent Classification (CPC) classifications, target contraceptive agent or approach, claimed mechanism of action, dosage form and route of administration, key embodiments/claims, and any disclosed experimental or clinical context relevant to male contraception. These data were cross-checked within each patent family to ensure internal consistency. The final corpus and extracted variables constitute the evidence base for the results and discussion presented in the manuscript (

Table 2. Patent applications for the most promising substances in studies for male contraception (period between July and October 2024).

Promising Substances	Quantity	Patents
Undecanoate dimethandrolone	1	US2008167283A1
118-methyl-19-nortestosterone	10	EP1846434A1 RS20050049A PL207582B1 HRP20050172A2 CN1923841A CN1257181C EP1212345A2 WO2021252761A2 CN1481388A CN101945853A
Reversible sperm inhibition under guidance	21	WO2016205239A1 US6011013A WO2023066923A1 WO2020167789A1 AU2016353345A1 WO0121829A1 US2004161824A1 WO2005019457A2 CN1840544A WO2023225692A1 WO2010014253A2 WO2005019448A2 US6610657B1 WO2005018657A2 WO2005018660A1 US2018028715A1 WO2022232259A1 US2005054576A1 CN1812746A CN115335367A WO0194621A1

). The majority of these patents (22; 68.8%) originate from the United States of America (USA), attributed to public health institutions (3), private companies (12) and universities (6). Germany follows with 5 (15.6%) patents, all from private companies (pharmaceutical sector). The Netherlands and China each contribute 2 (6.2%) patents filed by private companies, in pharmaceutical research. South Africa and Finland each have 1 (3.2%) patent, both from universities, demonstrating the contribution of academic research in these countries.

Based on these data, it is worth highlighting the high influence of private research in the development of these new substances, very focused and driven by the strong interest and profitable potential of the new drugs. Still regarding the disparity observed in the number of patents already registered by the United States American (USA) in comparison with other regions of the planet, its hegemony is expressive and understandable, since, since 2013, this country alone was already responsible for a total of 126,747 patents in the general pharmaceutical area. Furthermore, the significant volume of China and Germany stands out, with 39,460 and 32,534 patents, respectively, in the general pharmaceutical area, in current projects to prospect contraceptives for the male population [44]. There has been growing acceptance of male hormonal contraceptives by both men and women, overcoming social barriers [34]. Furthermore, this is in line with the growing demand for patents in this area, since, particularly in developed countries, it is possible to observe high rates of vasectomy and other methods of removal for unwanted pregnancies.

Male acceptance (70%) was achieved following treatment involving a quarterly injection and a daily transdermal dose of NMC [45]. In China, men described the NMC as “good news for women who do not want or can not use a female method”, but they considered widespread acceptance unlikely [46,47]. The men interviewed rated the new methods as “good” or “excellent,” but emphasized their lack of protection against possible sexually transmitted infections [17]. The development and approval of patents are of extreme importance, since world market reflects the great lucrative potential of these new drugs [48].

3.5. Sociocultural Approach to NMC

Table 3. Study variables related to the sociocultural aspects of the articles analyzed.

Authors/Year	Name/Type of Study	Number of Participants (n)	Main Results
Hamm et al. (2019) [49]	Men’s Fertility Attitudes and Behaviors (MFAB), qualitative study	58 low-income cisgender men	No influence on the choice of contraceptive methods and reproductive decisions (~50%) Known people who had already suffered some form of deception regarding contraception (46.55%). “It’s her body”: low-income men described feeling a lack of autonomy regarding pregnancy and fatherhood. The main reported factors were the belief that women should control contraception, reluctance to discuss the subject, the lack of acceptable male contraceptive methods, and fatalistic attitudes toward pregnancy.
Nguyen et al. (2023) [50]	Online cross-sectional survey with a Gender Equitable Men’s Scale (GEMS) Exploratory online survey on men’s willingness to use NMC and gender-equitable attitudes.	2066 cisgender men	“Couples should decide together whether they want to have children” (69%; 1466/2066) “Men should be tough” (46%; 944/2066) Willing to use a hormonal NAPCF (75%; 1540/2060) “Men should feel ashamed if they can’t maintain an erection” (>33.33%). Men’s willingness to use NMC is associated with their attitudes toward gender equality. 54% of men were willing to use a male hormonal method, and 65% were willing to use any type of new male contraceptive. Higher scores on the Gender Equity Measure for Men (GEMS) and prior experience with abortion were positively associated with the willingness to use NMC.
Newmann et al. (2021) [37]	Measuring men’s beliefs and gender norms related to contraception: development of the Male Norms and Family Planning Acceptance (MNFPA) scale.	150 men	Development and validation of the MNFPA scale. MNFPA scores were associated with greater self-efficacy and contraceptive intention. This indicates a greater perceived ability to use contraceptives and less difficulty accepting their use by a partner. There was no significant correlation between MNFPA scores and actual contraceptive use.
Newmann et al. (2023) [28]	Masculinity norms to improve men’s acceptance of contraceptive methods: results from a pilot intervention with men in western Kenya.	150 men (75 intervention/75 control)	Participation in the intervention was associated with increased scores on the MNFPA scale for contraceptive acceptance, including knowledge of contraceptive methods and discussions about contraception with partners and others. The intervention was not associated with increased behavioral intention or use of modern contraceptive methods. Men have the final say in contraceptive decisions (~50%)
Brewer & Nguyen (2025) [51]	Growing interest in new male contraceptive methods following the U.S. Supreme Court’s Dobbs v. Jackson decision.	Web traffic data and Google searches.	Following the Dobbs v. Jackson decision, there was an accentuated increase in Google search volumes for “male birth control” and traffic to related websites. The average number of searches increased significantly (45.4%) in the two weeks after the decision compared to the two weeks before (19.6%).
Gipson et al., 2025 [52]	Clinical trials on male hormonal contraceptives	30 men	There are many reasons why people use male hormonal contraceptives, including social concerns such as overpopulation and responsible pregnancy, partnership factors such as sharing contraceptive responsibility and concerns about the “trap,” and individual factors such as pleasure, intimacy, and bodily autonomy. Single men viewed male hormonal contraceptives as a form of protection, whereas men in committed relationships wanted to share responsibility and minimize potential side effects for their partners.
Jacobsohn et al., 2022 [53]	Male contraception is coming: who do men want to prescribe their contraceptive method?	124 men (participants in clinical trials on male hormonal contraceptives)	Most people chose to obtain male hormonal contraceptives from their regular doctor (43.5%) or community pharmacist (17.7%). Specialists in family planning, men’s health, reproductive health, or hormones were the least preferred. Participants with more education tended to prefer specialists more often.
Nguyen, 2024 [54]	Research using secondary data obtained from the U.S. National Survey of Family Growth	3340 respondents	Estimate the potential market for NMC in the EUA. 23.2% of men did not use any method of contraception during their last sexual encounter. A significant proportion of these men would be “very upset” if they got someone pregnant: 4.3% of those who do not use contraception and 19.7% of condom users. The potential market for NMC is estimated to be between 7 and 15.5 million men.
Nguyen, 2024 [34]	Review of more than 30 studies on the acceptability of male contraceptives versus male acceptance of contraceptive responsibility.	Own survey with 2066 men	Despite men’s consistent interest and willingness to use NMC, investments remain limited. Men’s views on their role in preventing pregnancy are shifting toward greater gender equality, which is reflected in their willingness to use NMC. Increase awareness among men about their reproductive freedoms. Men prefer to consult primary care physicians for NMC.
Gomez-Torres et al., 2023 [55]	Systematic review on the acceptability and determinants of NMC use from a gender perspective	-	The acceptability of NMC in men and women is high (over 70%). Acceptability is influenced by factors such as side effects, route and frequency of administration, efficacy, and cost. The use of NMC varies by country and culture. The daily NMC pill would be the most acceptable option for men. However, women would prefer a quarterly injectable MHC because they are concerned that men would forget to take the daily pill.
Blitzer, 2025 [56]	Theoretical essay on male contraception—Part of gender medicine and men’s reproductive rights	-	Two historical models of contraceptive practice overlap: the patriarchal model, in which men have exclusive control over reproductive decisions and women’s health is disregarded, and the female emancipation model, in which women have access to means of deciding whether to reproduce, such as the pill, which has reduced the cost for women to invest in their careers. The Collaborative Model is a future project in which both individuals decide together on reproduction and the methods to use. This increases choice and awareness of shared responsibilities.
Kidula et al. (2025) [57]	Review and synthesis of published literature on the impacts of male contraception on global sexual and reproductive health and rights	-	Global policies and structures neglect men’s sexual and reproductive health, and data on the topic is scarce. Failing to address men’s sexual and reproductive health perpetuates the sexual and reproductive burdens faced by women. Advances in male contraception can raise awareness of and investment in men’s sexual and reproductive health. This promotes gender equality and shared responsibility in preventing pregnancy, sexually transmitted infections, and human immunodeficiency virus (HIV) infection.

presents the sociocultural aspects for NMC. A qualitative study interviewed 58 low-income men about their perspectives on contraception, pregnancy, fatherhood, and relationships. The goal was to better contextualize reproductive decision-making in low-income and minority populations. Men often share the idea that women are responsible, or should be, especially in controlling contraception and pregnancy [49]. In this context, the study presents a certain urgency with the need to increase male contraceptive options, as well as encourage the transformation of male gender norms to encourage men to consider contraception as being within their competence and involve them in reproductive decision-making.

The willingness of cisgender men was examined to use an NMC in relation to their attitudes about gender equality (i.e., gender roles, relationships, masculinity, and sexuality) [50]. However, the development of male contraceptives continues to be limited by investors’ and industries’ doubts about cisgender men’s willingness to use these new contraceptives and tolerate their potential side effects. Respondents who reported a willingness to use an NMC (hormonal or non-hormonal) achieved higher gender equity scores (GEMS total score: 48.3 ± 7.7 vs. 44.4 ± 5.6, p < 0.001). These results suggest that efforts to develop NMCs may benefit from technological innovations and therapeutic strategies that are both effective contraceptives and have fewer undesirable effects. These efforts could also benefit from sociocultural changes, specifically regarding men’s views on gender roles and masculinity. A masculinity-based instrument was developed to measure men’s acceptance of contraceptives [28,37]. However, about half of the men “strongly” agreed or agreed that the man has the “final say” in contraceptive decisions. This is contrary to a survey conducted by Nguyen et al. (2023) [50], in which the majority of respondents said that contraceptive decisions are made jointly with women.

Sociocultural findings reveal that gender norms influence acceptance of male contraception. Many men consider this responsibility to be women’s alone. Men who demonstrate egalitarian attitudes and participate in family planning, such as expressing interest in contraceptive counseling, represent a growing proportion of those willing to use new contraceptives [50]. However, there are concerns about side effects, particularly hormonal ones, as well as the lack of protection against sexually transmitted infections. The research underscored the importance of including other gender identities beyond cisgender men to foster a more inclusive perspective.

Considerable interest and a high willingness to use new NMC (reaching over 70% in some studies) have been observed among men (and women for their partners) [52,54,55,56]. A systematic review confirmed this high acceptability, with data primarily from Europe and North America [55]. It projects a potential U.S. market of seven to 15.5 million men who would use NMC, depending on the switching method criteria [54]. This demand is corroborated by in-depth, qualitative interviews with clinical trial participants who used NMC [52]. These interviews revealed individual and partnership-related motivations. The main social reasons are linked to men’s greater involvement and shared contraceptive responsibility, financial interference with the ideal time to have children, and concerns about well-being and adequately caring for a child at the right time. Therefore, the need for men to have greater reproductive autonomy through NMC is evident.

Despite a general trend toward more equitable attitudes, some traditional gender norms persist. For instance, studies demonstrated that even when men are more accepting of contraceptives, some still believe that women should ask their partners for permission to use them or that men should have the final say in family planning decisions [28,37]. This perpetuates the patriarchal model of contraceptive practice. Historically, contraceptive responsibility has fallen on women [55,56,57]. Meanwhile, low-income men often lack reproductive autonomy, which reinforces the idea that women are in control of pregnancy prevention [49]. This norm structures the model of female emancipation through contraceptive practice. However, views on male roles are shifting toward greater gender equality and shared reproductive responsibility, representing the collaborative model of contraceptive practice [50,52,54]. The development and widespread availability of NMC can serve as tools to achieve gender equality in reproductive rights and responsibilities [49,54,55,56,57]. Following the U.S. Supreme Court’s decision in Dobbs v. Jackson (which overturned federal protections for abortion), there have been reports of increased public interest in male contraception (including vasectomies and new methods) [51,54]. This suggests greater male awareness of threats to reproductive freedoms and a desire for greater autonomy.

Concerns about side effects, especially those affecting male identity and sexual function, are a barrier to accepting NMC for both the industry and men themselves [50,55,56]. However, a clinical trial was published in which 80% of men and women reported satisfaction and willingness to use the method if available, despite adverse effects that led to discontinuation [54]. This suggests that users’ perception of “acceptable risk” may differ from that of development and safety committees, especially when the benefits of shared responsibility and reproductive autonomy are prioritized.

As for barriers to development and access, the pharmaceutical industry is perceived as reluctant to invest in NMC due to the high costs of research and development, the availability of female methods, and concerns about male acceptance. This resistance is based on the belief that men will not use the method, will be afraid of side effects, or that women will not trust it [56]. This persistence of doubt despite the evidence suggests deeply rooted prejudices about male reproductive responsibility [54]. Much of the evidence of acceptability is based on “hypothetical use” [55], which may not directly translate into actual use. However, participants in a clinical trial who actually used an NMC helped fill this gap [52].

The main barriers to researching, producing, and accessing male contraceptives are regulatory and scientific challenges, as well as the reluctance of the pharmaceutical industry [58]. The main challenge is the lack of clear guidelines and regulatory precedents for approving NMC due to uncertainty about its clinical efficacy and the absence of a consensus on surrogate markers. The effectiveness and results of NMC are measured in cisgender women who are in a relationship with cisgender men, and not in men themselves, as the outcome of pregnancy in the female body is analyzed. This complicates the development of a male contraceptive because the effectiveness of the treatment in preventing pregnancy is not measured in the man receiving it. Therefore, the consent of the female partner is required for inclusion in NMC studies. In addition, neither the FDA nor the European Medicines Agency (EMA) has publicly stated whether a surrogate biomarker of efficacy would be acceptable for marketing approval. Although the WHO and expert groups have recommended using a very low sperm concentration (less than 1 million/mL) as the primary endpoint for pregnancy prevention, product developers still face regulatory uncertainty regarding the acceptance of this threshold in Phase III (registration) studies [58].

The literature has also highlighted specific challenges associated with different methods. Clinical trials involving hormonal methods should monitor specific adverse events such as acne, changes in libido and mood swings. Although a reversible decrease in testicle size is a sign of effectiveness, adequate counseling is required to reassure men that the change is temporary. A different set of evidence is required for the approval of new products using non-hormonal methods. These types of approach present a significant challenge due to the lack of precedents and information on potential biomarkers based on the mechanism of action. And, in relation to reversible vaso-occlusive methods, new devices for vascular occlusion (alternatives to vasectomy) also lack regulatory precedents. In these cases, the validation of new biological markers (in addition to sperm count, such as motility or sperm function) is necessary, which is a challenging and laborious process [58].

This discussion has highlighted that the lack of involvement by pharmaceutical companies results in limited options and inequalities for men. The main arguments or beliefs that lead to this industrial reluctance are: (1) potential side effects that may lead to low adherence. This is related to the belief that men ‘will not use it because they are afraid of the side effects and short- and long-term risks, and will not accept these risks, which are new to them; (2) the difficulty of producing and researching methods, as there is a perception that male reproductive processes are ‘more difficult to control’ in order to produce short-term, reversible and highly effective methods; (3) the high cost of development, which requires ‘large clinical trials’ that are considered ‘extremely expensive’; (4) mistrust of partners (cisgender women), due to the belief that ‘women do not trust men’ and that women are ‘victims of the method’s failure’, which would discourage investment in research; (5) psychological factors, due to the assumption that men will not use methods for psychological reasons, such as fear of affecting their masculine identity, ambivalence, or desire to avoid new responsibilities. Thus, regulatory uncertainty is just one of many potential obstacles to be overcome in developing male contraceptive products [58].

Poor infrastructure and a shortage of qualified health professionals capable of delivering effective male sexual and reproductive health services also pose challenges. In the face of so many challenges, the importance of the NMC prescriber and the health service through which these drugs will be offered stands out [57,58,59,60,61]. Men prefer to obtain NMC from family doctors (general practitioners) or community pharmacists rather than from specialists, such as urologists or endocrinologists. This preference contrasts with the environment of specialist-led clinical trials and the current structure of procedures such as vasectomy, which are predominantly performed by urologists [53]. There is a lack of adequate medical training and a shortage of specialists in male sexual and reproductive health in primary care units [57]. This raises the question of how the health system will adapt to meet men’s preference for primary care professionals for NMC.

The development of NMC, whether hormonal, non-hormonal, or vaso-occlusive, faces an unprecedented lack of regulatory procedures and guidelines from the FDA and EMA regarding the evidence required for marketing approval. In addition to the issues already reported regarding the search for surrogate markers and measuring the effects of the intervention on women in heterosexual relationships, the lack of a clear precedent means that developers have to consider demonstrating the pregnancy rate of partners, which is more expensive and time-consuming. The challenge for non-hormonal methods is even greater, as there are no precedents. In order to enter clinical efficacy trials, new biological markers capable of determining the suppression of a specific sperm function (such as motility, capacitation, or acrosome reaction) must be validated. As NCM will be used by healthy individuals over extended periods, the FDA and EMA recommend collecting safety data from 1500 men exposed to the experimental drug. Full reversibility of sperm suppression must be demonstrated in phases II and III of clinical studies. The acceptable recovery goal is for the sperm concentration of 95% of the male population studied to return to the normal range for adult men within 6 to 12 months [58].

Men’s willingness to use NMC is associated with more equitable attitudes towards gender. Therefore, efforts to increase uptake should focus on sociocultural changes that challenge restrictive notions of masculinity. Men who participated in clinical trials viewed male contraceptives as a means of gaining greater control and avoiding pregnancy by untrustworthy partners. However, a new ethical debate arises with the possibility of a man using a method ‘secretly’ (i.e., covertly) without his partner’s knowledge, which is a new concept for men. While the ultimate goal is mutual responsibility, there is a risk that male involvement in contraception could lead to reproductive interference or coercion against women in some cases [54,55,56,57,58].

To ensure universal access, it is essential that men’s sexual and reproductive health, including male contraception, is included in global, national and local health policies, as well as in the Health Benefits Package (PBS) of Universal Health Coverage (UHC) and the Brazilian Unified Health System, and all other universal systems worldwide. This will mitigate direct expenses for users [50,58]. Introducing NCM requires strengthening health systems and preparing health professionals to integrate male sexual and reproductive health, as NCM can encourage men to seek preventive health services.

4. Conclusions

According to the reviewed studies, all of the tested chemical substances have contraceptive potential and show promise for the development of NMC. Most of the studies were classified as Phase I, requiring further clinical studies and evaluation. These studies have limited analysis because they involve a small number of participants and are carried out over a short period (up to 28 days). New studies with larger samples, long-term follow-up, and reversibility tests indicate the necessity of technological advances in the progression of clinical studies of male contraceptives. However, the studies emphasized the need for new studies with larger samples, long-term follow-up, and reversibility studies for RISUG. There is a global social need for equal access to contraceptives and options for both men and women. The studies and patents demonstrated positive effects on the acceptance and knowledge of masculinity-driven contraceptives. Furthermore, creating a cultural environment of gender equality and redefining what is understood as masculinity will facilitate acceptance when NMC reach the market.

Optimism about the demand for and potential of NMCs to rebalance reproductive responsibilities is growing, driven by social changes and events such as the Dobbs v. Jackson decision, eliminating the constitutional right to abortion in the United States. The ruling removed the ‘rebalancing’ that had historically taken reproductive autonomy into account. This enabled the legal framework to shift towards state-level restrictions and a greater emphasis on state authority in medical practice. And, this could have consequences for reproductive equity and access to care. However, this progress is challenged by deeply held beliefs about gender roles in industry and society, as well as by regulatory and systemic barriers in the healthcare field. Widespread availability and adoption of NMCs will require overcoming many of these perceived and real barriers, making it a preventative behavior.

The development of male contraception can be compared to an orchestra preparing for a new symphony. The sheet music (the need and demand) is clear, and many musicians (researchers and participants) are eager to perform. However, some members of the orchestra, such as industry and regulatory agencies, are accustomed to old melodies and are reluctant (or do not know how) to provide new instruments that sometimes sound out of tune. For the symphony to succeed, the instruments must be tuned, the musicians must rehearse, and all musicians must understand and embrace the new composition. They must adapt their roles to create complete and equitable harmony.