Plant-Based Contraceptives on the Horizon

Hormone-based contraceptives can cause adverse events in women, including weight gain, nausea, and mood changes. Some women may even experience more severe adverse events, such as stomach or chest pain. These side effects may make obtaining contraceptives difficult for some individuals.

The authors of a new study published by the Proceedings of the National Academy of Sciences have discovered that 2 chemicals commonly used in folk medicine may prevent the fertilization of an egg. As an added benefit, the chemicals were observed to be effective at low doses.

The chemicals work by preventing sperm from pushing through the cells surrounding the egg and the membrane. This action is typically stimulated by progesterone, which is secreted by the cells around the egg to make the sperm propel forcefully.

"Because these 2 plant compounds block fertilization at very, very low concentrations -- about 10 times lower than levels of levonorgestrel in Plan B -- they could be a new generation of emergency contraceptive we nicknamed 'molecular condoms,'" said researcher Polina Lishko, PhD. "If one can use a plant-derived, non-toxic, non-hormonal compound in lesser concentration to prevent fertilization in the first place, it could potentially be a better option."

The authors hypothesize that the chemicals could be used as a permanent contraception or as emergency contraception. Since sperm takes 5 to 6 hours to mature once inside of the female reproductive system, the drug has enough time to block fertilization.

The investigators studied different factors in reproduction, including the hormones that trigger sperm to swim towards the egg. Once the sperm reaches the protective cluster of cells surrounding the egg, the tail of the sperm operates in a whiplike motion to enter the egg, according to the study.

The powerkick used to enter the egg is the result of calcium flooding the tail from the opening of the CatSper calcium channel.

"The massive influx of calcium into the sperm tail changes the sperm tail's beating pattern, making it highly asymmetrical," said first author Nadja Mannowetz, PhD. "This asymmetrical bending gives the sperm cell enough force to drill through the tenacious egg vestment."

The authors discovered that progesterone opens the channel by binding to the ABHD2 protein. Then, they began looking for other chemicals that would open or block the channel.

In the new study, the authors examined testosterone, estrogen, and cortisol. They found that all 3 competed with progesterone and blocked tail whipping, according to the study. However, only testosterone and cortisol were observed to be effective at normal hormone levels.

The authors believe that their findings may explain why women with high levels and/or testosterone and stress may have decreased fertility.

Additionally, another hormone, pregnenolone, was also found to trigger tail whipping.

Additionally, the investigators explored natural contraceptives used by indigenous people around the globe, which revealed multiple non-steroid chemicals similar to the steroids that bind to ABHD2 and block the calcium channel.

One of the chemicals—pristimerin—from the plant Tripterygium wilfordii, has been used in Chinese traditional medicine as an antifertility drug. Another chemical—lupeol—is derived from the mango and dandelion root, and was not believed to have contraceptive properties.

The investigators discovered that both pristimerin and lupeol blocked progesterone from binding to ADHD2 and prevented fertility, according to the study.

"These compounds not only blocked calcium channel activation, but also blocked sperm hyperactivated motility, reducing their activity to the level of nonactivated sperm cells," Dr Lishko said. "It doesn't kill sperm basal motility. It is not toxic to sperm cells; they still can move. But they cannot develop this powerful stroke, because this whole activation pathway is shut down."

The authors are now testing the efficacy of these chemicals in in vitro models of human sperm and are searching for low cost versions of the chemicals, the study concluded.