In 1960, the US Food and Drug Administration (FDA) approved the first formulation of oral contraceptive for women, consisting of synthetic estrogen and progestin components. This was a huge development, carrying major societal consequences. In fact, historians of the mid 20th century have sometimes suggested that advent of “the pill” —which, early on, referred to a handful of different oral contraceptive regimens and now consists of numerous— carried major societal consequences. In a very real sense, oral contraception was a liberator. Extremely effective when taken correctly, and made increasingly safer over the years and decades through adjustments of formulations and dosages, oral contraceptives enabled women and their male partners to plan reproduction much more easily than they could previously. Early on this led to the Supreme Court of the United States (SCOTUS) to declare the right of married couples to use contraception in the Griswold versus Connecticut case of 1965. Oral contraception has been a long and eventful history that today has reached a strange point in which there is concern that the SCOTUS might overturn Griswold in some way by applying the same rationale that it applied in the recent (2022) Dobbs versus Jackson Women’s Health Organization case that overturned the 1973 Roe versus Wade decision that had protected the right to abortion..
But amidst all of the ups and downs since oral contraceptives entered the market nearly six decades ago, there has been a goal, a longing for another type of oral contraception — a male type. Would it be possible to create a medication that men could take as birth control? Scientists have been working on this for all those six decades and for most of that time, it seemed like it was always more than a decade ahead, and then something didn’t work. Given that the female oral contraceptive strategy is a hormonal one, much of the early research for male contraception has also been hormonal, but this has been problematic. Giving hormonal treatment aimed at making men temporarily infertile, means pushing back against male hormones. This can cause impotence and carries various other undesirable effects, like reducing or eliminating secondary male characteristics and other systemic problems. This has made male oral contraception more challenging than female oral contraception, which involves giving female hormones in a way that interferes with the timing of those hormones so as to prevent ovulation.
Consequently, for all of these years, options for male contraception have been limited to a barrier method, meaning condoms, or permanent sterilization to prevent conception and consequently to prevent pregnancy. Male sterilization means vasectomy, in which a surgeon cuts the vas deferens in order to prevent sperm traveling from the testes to merge into the ejaculation fluid on its way from the prostate. Effectiveness of vasectomy is more than 99 percent and actually the failure rate is only 1 per 2,000 procedures, but it is permanent. Reversal procedures are possible, but often not successful, so vasectomy is not a good option for a male who is not ready to reproduce and wants to father children later. For such men, there has been a goal-to find a non-hormonal medication strategy that could render males infertile and in a reversible way, and finally such a medication seems to be on the horizon.
Conducted by scientists in Europe and at Weill Cornell Medicine in New York and published recently in the prestigious journal Nature Communications, a new study has demonstrated a medication that renders sperm cells immobile, preventing pregnancy when given to male mice. The basis of the medication is that sperm require adenylyl cyclase (sAC), a protein that enables them to swim. Men with rare genetic mutations in which sAC is abnormal are infertile, because getting sperm into the vagina is not enough, particularly for humans. It’s actually easier for mice to get pregnant, because the mouse vagina and uterus are continuous with not much barrier between them. As a human woman, however, you have a cervix through which sperm must pass and there is limited time. Except during and right after sexual intercourse, the vagina has a very acidic environment, a low pH, that is not friendly to sperm. Those sperm have to swim to the cervix and through it before the environment in the vagina becomes hostile. Then, they have to swim all the way across the uterus to the fallopian tube to meet up with an ovum. While mice sperm don’t need to swim as much as human sperm, even mice sperm were affected in a major way by the anti-sAC drug. Two hours after mice had received the drug, sperm mobility was down to about 6 percent of normal and the drug was 100 percent effective in preventing pregnancy. Over the period from 2 to 24 hours after the medication was given, the effectiveness waned and by 24 hours the effects wore off completely. The drug works, because it is acting on mature sperm located in a system of tubes outside the testicle, called the epididymis, where they wait to be ejaculated. Basically, this is a short-acting medication that, if effective in humans, could be something that men take to achieve contraception rapidly and whose effects reverse very quickly after the last dose is taken. The researchers are so optimistic about the results in the mice study that human trials could begin as soon as 2025.
Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, Huggins DJ, Steegborn C, Miranda IC, Meinke PT, Buck J, Levin LR. On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun. 2023 Feb 14;14(1):637. doi: 10.1038/s41467-023-36119-6. PMID: 36788210.