Used for centuries by African hunters, poisonouabin it became an inspiration to create a new way to reversibly limit male fertility. To what extent is the new method effective and what chance does it have to accept?
Often modern methods of contraception are compared to shooting with sharp bullets to a person in a bulletproof vest. The responsibility for using the majority of contraceptives available on the market lies with women: typically only contraception remains the use of condoms, vasectomy and abstinence.
Attempts have been made to create a male hormonal contraception in the shape of this woman. The effectiveness of the new method, consisting of administering two hormonal injections to the masters, was comparable with the results achieved for a female contraceptive pill. 320 volunteers from Europe, North America and Australia who remained in monogamous heterosexual relationships, aged 18-45, took part in clinical trials. For 26 weeks, gentlemen were given three series of two hormonal injections: the first one with progestagen (affecting the pituitary gland reduces the number of sperms produced), the second with a testosterone derivative (to reduce the side effects of the therapy). In 96 percent of participants in the study, the number of sperms decreased to a level that did not give practically the chance of fertilization. Then every 8 weeks for a year the gentlemen took injections to maintain the effects of therapy. During this time only 4 pairs were born. Gentlemen, however, reported many side effects: changes in mood, muscle pain or increased libido. The authors of male hormonal contraception are now working to reduce the nuisance of therapy.
An alternative to interfering with male hormones may be temporarily limiting sperm motility. The inspiration for her was African poisonouabainused by hunters during hunting. Its active substance is strofantine, a fast and potent inhibitor of the sodium potassium pump. The soda-potassium pump itself consists of two subunits: α and β. Strofantine acts on the α-subunit, which results in blocking the pump and increasing the concentration of ions in the cell. In the case of myocardial tissue, such a blockage can cause very strong contractions, which is why the animals poisoned by the poisoned arrow fall due to cardiac arrest. The effect of strophantine on the sodium-potassium pump made it found in low concentrations in medicine for the treatment of cardiac arrhythmias and hypertension.
It may turn out that this is not the end of the medical career of strophantine. Researchers at the University of Minnesota decided to use chemically modified strophantin as a precise, male contraceptive. Sperm, like other body cells, use the action of a sodium-potassium pump. However, the α-subunit in spermatozoa is differently constructed than in other cells of the body. This difference inspired scientists to look for this derivative of strophantin, which could selectively affect the α-subunit of the sodium-potassium pump, present in male reproductive cells.
In rats - success
Researchers have created several chemical structures based on strophantin, which are capable of blocking the α-subunit only in sperm cells. They gave them to rat sperm and noticed that sperm motility was inhibited. Then the modified strophantin was given to live rodents. This did not cause any symptoms of poisoning, sperm production remained normal. The only effect that was achieved was that the sperm were half less active than the controls.
It seems that the path to the male contraceptive pill on the basis of chemically modified strophantin is still far away. However, the authors of the study emphasize that their discovery may open a new gate in research on male contraceptives.
S. S. Syeda, G. Sánchez, K. H. Hong, J. E. Hawkinson, G. I. Georg, G. Blanco, Design,Synthesis, and in Vitro and in Vivo Evaluation of Ouabain Analogues as Potent and Selective Na, K-ATPaseα4 Isoform Inhibitors for Male Contraception.J. Med. Chem. (2018)