Contraception research: from the pill to male methods and wildlife

Contraception research takes what is known about reproduction and looks for points where it can be interrupted safely and, usually, reversibly. The public health stakes are large. According to the World Health Organization (WHO), of the 1.9 billion women of reproductive age worldwide in 2021, 874 million were using a modern contraceptive method and 164 million had an unmet need for contraception.

The journals behind this archive published contraceptive research from the 1960s onwards: steroid compounds tested in laboratory animals, candidate male antifertility drugs, studies of men after vasectomy, and vaccines tested in monkeys, horses and other species. The sections below set that work in its wider context.

Where contraception can act

Biologically, pregnancy can be prevented at several stages: by stopping the release of eggs (ovulation), by stopping sperm production, by blocking the passage of sperm, or by preventing sperm and egg from meeting and fusing. WHO groups current methods by how they are used and how reliable they are:

• highly effective, long-lasting methods: implants, intrauterine devices and sterilisation;
• methods that are effective when used correctly and regularly: pills, injections, patches and vaginal rings;
• barrier methods: condoms, which are also the only method that protects against sexually transmitted infections, including HIV;
• less reliable methods: fertility awareness-based methods and withdrawal.

The pill and the hormonal era

The oral contraceptive pill, first introduced around 1960, works mainly by preventing ovulation. A historical review written for its fiftieth anniversary notes that it was developed before the regulation of ovulation and the menstrual cycle was fully understood. It depended on earlier animal experiments on the effects of sex steroids and on the chemical synthesis of steroid compounds that work when taken by mouth. The review credits a small group of people for its development: the campaigners Margaret Sanger and Katharine McCormick, the biologist Gregory Pincus and the gynaecologist John Rock.

The first pills contained high doses of hormones, and serious side effects soon emerged. This led to preparations with less oestrogen, more selective progestogens and new ways of delivering the hormones. The history illustrates a recurring theme in the field: an effective method is only the start, and its safety profile is refined over decades of use.

Male methods: vasectomy and hormonal approaches

For men, the established options remain condoms and vasectomy. Vasectomy, or male sterilisation, is a permanent method: a minor operation, usually under local anaesthetic, that stops sperm being ejaculated. The NHS notes that reversal is possible but does not always work, and that vasectomy gives no protection against sexually transmitted infections.

A reversible male hormonal method has been pursued since the 1970s. The principle is to give hormones, testosterone alone or combined with a progestogen, that make the brain reduce its output of LH and FSH, the pituitary hormones that drive sperm production. This lowers testosterone inside the testis, where it is normally many times higher than in the blood, and spermatogenesis slows or stops, while the testosterone given covers the needs of the rest of the body. The usual target is a sperm concentration below 1 million per millilitre.

Large trials have shown that the approach can work. In a WHO multicentre trial reported in 1990, 157 of 271 men (65%) stopped producing sperm in the ejaculate within six months, and only one pregnancy occurred during the twelve-month efficacy phase. Response rates differed between populations: in that trial, 91% of men at Chinese centres reached this point, compared with 60% at non-Asian centres. In a later phase III trial of monthly testosterone undecanoate injections in 1,045 men, about 95% reached very low sperm counts or none at all. A later WHO study combining two injectable hormones was stopped because of side effects, including mood changes. Current candidates include a gel combining testosterone with the progestin Nestorone (segesterone acetate), and two oral compounds, DMAU and 11β-MNTDC. None has yet been approved, and larger, longer trials are still needed.

Immunological approaches and contraceptive vaccines

Another line of research uses the immune system. If the body can be prompted to make antibodies against a protein essential for reproduction, fertility can be blocked without daily hormones. Two targets have dominated: the zona pellucida, the protein coat around the egg that sperm must bind to and cross, and gonadotrophin-releasing hormone (GnRH), the brain hormone that sets the whole reproductive axis in motion. Other projects have looked for proteins added to sperm as they mature in the male ducts, with the aim of blocking sperm function without affecting hormones.

Contraception for wildlife

The clearest practical success of contraceptive vaccines has been in animals. Lethal culling is not always legal, safe or publicly acceptable, and immunocontraception offers an alternative for managing some wildlife populations. A 2011 review reported contraceptive success in more than 85 wildlife species, with vaccines based on porcine zona pellucida (PZP) and on GnRH. Population-level programmes have focused on wild horses, urban deer, bison and African elephants. The same review lists the remaining challenges: efficacy varies between species, safety during pregnancy must be established, wary free-ranging animals need suitable delivery systems, and some vaccines can affect behaviour.

What is established and what is debated

• Established: hormonal suppression of ovulation is effective and widely used; vasectomy is an effective permanent method; hormonal suppression of sperm production can prevent pregnancy in trials; zona pellucida and GnRH vaccines can control fertility in many animal species.
• Still open: whether a male hormonal method will combine reliability, acceptable side effects and full reversibility well enough to reach the market; why men differ in how they respond; and how to make wildlife vaccines safe and practical across species.

This page describes research and its history. It is not advice on choosing a method; that is a matter for a doctor, nurse or sexual health service.