Despite increased access to contraception
over the last 60 years,
unplanned pregnancies continue to contribute to economic disparities
and overpopulation. Additionally, the burden of family planning falls
primarily on women, as a reliable pharmaceutical male contraceptive
has yet to be developed. The objective of this literature-based systematic
review was to identify compounds for future study from natural sources
with potential nonhormonal male contraceptive activity. After the
exclusion of extracts and compounds with known hormonal mechanisms,
26 unique compounds were identified from natural species. The plant
source, compound class, structure, target, mechanism of action, safety/toxicity
profile, and in vitro, in vivo, and human studies for each compound
were evaluated and discussed. β-Caryophyllene, embelin, oleanolic
acid, triptonide, and N-butyldeoxynojirimycin (NB-DNJ)
were selected as the five most promising compounds for future study
using prespecified criteria such as number of studies, efficacy and
safety profile, reversibility, and previous use in humans for any
indication. In order to move forward with development of a male contraceptive
from a natural source, additional studies are needed to determine
the predicted safety and efficacy for in vivo and human clinical trials.