News | Nonhormonal Male Contraceptive Was 99% Effective Without Side Effects in Mice
At the American Chemical Society (ACS) Spring 2022 meeting, University of Minnesota researchers announced a nonhormonal oral male contraceptive that was 99% effective in mice with no apparent side effects. The finding could offer men a reversible, safe, hormone-free contraceptive option and reduce the long-standing contraceptive burden on women.
Limited male options create an unequal burden
Women have many contraceptive options, including oral pills, patches, and intrauterine devices, while men remain limited to condoms and vasectomy. Condoms may be used incorrectly or fail, while vasectomy is considered permanent or difficult to reverse. This lack of options has left women carrying much of the responsibility for contraception.
A nonhormonal approach may avoid side effects
“Scientists have been trying to develop an effective oral male contraceptive for decades, but none has been approved,” said project co-leader Md Abdullah Al Noman, a doctoral student at the University of Minnesota College of Pharmacy. Most male contraceptives in clinical trials target sex hormones such as testosterone, but may cause weight gain, depression, and increased low-density lipoprotein (LDL) cholesterol.
“We wanted to develop a nonhormonal male contraceptive to avoid these side effects,” Noman said.
Targeting RAR-α to suppress fertility selectively
The team focused on retinoic acid receptor alpha (RAR-α), one of three retinoic acid receptors. Retinoic acid, a form of vitamin A, plays an important role in cell growth and differentiation, including sperm production, and embryonic development. Earlier research found that deleting the RAR-α gene in male mice caused infertility without obvious health effects.
By analyzing differences in the crystal structures through which RAR-α and the related receptors RAR-β and RAR-γ bind retinoic acid, the team screened and synthesized about 100 candidate compounds. They selected YCT529, which inhibits RAR-α nearly 500 times more strongly than RAR-β and RAR-γ, demonstrating high selectivity.
Mouse study: 99% contraception after four weeks
After male mice took oral YCT529 for four weeks, their sperm counts fell significantly and the drug was 99% effective in mating trials, with no visible side effects. Fertility fully returned 4 to 6 weeks after treatment stopped, showing good reversibility.
Human clinical trials expected within the year
According to co-leader Dr. Gunda Georg of the University of Minnesota College of Pharmacy, human clinical trials of YCT529 were expected to begin in the third or fourth quarter of 2022. “Although the animal results are encouraging, effectiveness in humans remains uncertain,” Georg said. The team is also exploring next-generation candidates by optimizing the current compound or developing drugs with new chemical scaffolds to further improve effectiveness and safety.
The researchers hope their work will overcome long-standing technical barriers to an oral male contraceptive and support a more equal distribution of contraceptive responsibility worldwide.
News | Nonhormonal Male Contraceptive Was 99% Effective Without Side Effects in Mice
News | Nonhormonal Male Contraceptive Was 99% Effective Without Side Effects in Mice
At the American Chemical Society (ACS) Spring 2022 meeting, University of Minnesota researchers announced a nonhormonal oral male contraceptive that was 99% effective in mice with no apparent side effects. The finding could offer men a reversible, safe, hormone-free contraceptive option and reduce the long-standing contraceptive burden on women.
Limited male options create an unequal burden
Women have many contraceptive options, including oral pills, patches, and intrauterine devices, while men remain limited to condoms and vasectomy. Condoms may be used incorrectly or fail, while vasectomy is considered permanent or difficult to reverse. This lack of options has left women carrying much of the responsibility for contraception.
A nonhormonal approach may avoid side effects
“Scientists have been trying to develop an effective oral male contraceptive for decades, but none has been approved,” said project co-leader Md Abdullah Al Noman, a doctoral student at the University of Minnesota College of Pharmacy. Most male contraceptives in clinical trials target sex hormones such as testosterone, but may cause weight gain, depression, and increased low-density lipoprotein (LDL) cholesterol.
“We wanted to develop a nonhormonal male contraceptive to avoid these side effects,” Noman said.
Targeting RAR-α to suppress fertility selectively
The team focused on retinoic acid receptor alpha (RAR-α), one of three retinoic acid receptors. Retinoic acid, a form of vitamin A, plays an important role in cell growth and differentiation, including sperm production, and embryonic development. Earlier research found that deleting the RAR-α gene in male mice caused infertility without obvious health effects.
By analyzing differences in the crystal structures through which RAR-α and the related receptors RAR-β and RAR-γ bind retinoic acid, the team screened and synthesized about 100 candidate compounds. They selected YCT529, which inhibits RAR-α nearly 500 times more strongly than RAR-β and RAR-γ, demonstrating high selectivity.
Mouse study: 99% contraception after four weeks
After male mice took oral YCT529 for four weeks, their sperm counts fell significantly and the drug was 99% effective in mating trials, with no visible side effects. Fertility fully returned 4 to 6 weeks after treatment stopped, showing good reversibility.
Human clinical trials expected within the year
According to co-leader Dr. Gunda Georg of the University of Minnesota College of Pharmacy, human clinical trials of YCT529 were expected to begin in the third or fourth quarter of 2022. “Although the animal results are encouraging, effectiveness in humans remains uncertain,” Georg said. The team is also exploring next-generation candidates by optimizing the current compound or developing drugs with new chemical scaffolds to further improve effectiveness and safety.
The researchers hope their work will overcome long-standing technical barriers to an oral male contraceptive and support a more equal distribution of contraceptive responsibility worldwide.
Source:
Collected online