Contraception: Beyond the Pill
Introduction
In 2010, the United States celebrated the 50th anniversary of the oral contraceptive pill. Created in 1960 by Margaret Sanger and Katherine McCormick, the oral contraceptive pill was the first form of safe, effective contraception that enabled women to control their reproductive cycles (1). Today, 100 million women use a form of the oral contraceptive pill to prevent pregnancy; the oral contraceptive pill is the contraceptive of choice for about 30% of women using contraception (2,3). The other 70% of women choose from a variety of other contraceptive options, including non-oral hormonal contraceptives, non-hormonal contraceptives, and permanent sterilization. This article will focus on the current options for non-permanent contraceptives and potential future contraceptives.
Contraceptives aim to prevent the fusion of an egg and a sperm by inhibiting one or multiple steps involved in fertilization and implantation. For fertilization to occur, first, the male must produce viable sperm. Sperm are formed in the testes throughout a male’s reproductive life (4). During sexual intercourse, the sperm travel through the epididymis and vas deferens, and are ejaculated through the urethra into the female (4). On average, over 100 million sperm are present in the ejaculate, but most are incapable of fertilization due to poor motility or immaturity; 85% of the sperm are incapable of traveling to the egg (4). Once inside the female reproductive tract, the sperm must journey across the cervix and through the uterus to the fallopian tubes where the sperm might find an egg (5). Sperm have a lifespan of 12-48 hours depending on the environment encountered in the female reproductive tract, so for fertilization to occur, the female must either have recently ovulated or release an egg while sperm are present in the reproductive tract (5). Ovulation is controlled by female hormones, specifically luteinizing hormone (LH) and progesterone (6). A surge of LH midway through the menstrual cycle triggers ovulation in women, leaving them at their most fertile (6,7). As the egg travels down the fallopian tube, progesterone levels increase, causing the endometrial lining to thicken to facilitate implantation of a fertilized egg (6). Without the lining, implantation cannot occur, and the egg, even if fertilized, will pass out of the female reproductive tract. In summary, successful fertilization is the result of many events happening at precise times under precise conditions. Contraceptives alter the timing of these events, or the environmental conditions, to disrupt and prevent fertilization.
Hormonal Contraceptives
Since the days of Sanger and McCormick, a variety of hormonal contraceptives has been developed. Today, the most commonly used contraceptive is the oral contraceptive pill. In his book The Pill: A Biography of the Drug That Changed the World, Bernard Asbell argues “the Pill has been swallowed as a daily routine by more humans than perhaps any other prescribed medication in the world” (1). After the first oral contraceptive pill was developed and approved by the FDA, in only five years, one in four married women had used it (1). Today, 100 million women utilize the drug due to its high rate of effectiveness and safety (3).
The oral contraception pill exists in two main forms: progestin-only pills and combined hormonal pills. Combined hormonal pills contain daily doses of progestin and estrogen and usually come in packs of 28 or 21. Both packs have 21 pills that contain active hormone, but where the last seven pills of the 28-pack are inert, 21-pill packs recommend a seven-day period of no pills (8). The seven days without active hormone allow for shedding of the endometrial wall to convey a semblance of the natural menstrual cycle (8). However, the FDA has recently approved several extended cycle pills, which contain lower doses of hormone and can be used without the week of placebo pills to postpone or fully eliminate withdrawal bleeding (9). In combined pills, the progestin keeps LH levels low so that ovulation does not occur, thickens cervical mucus so that sperm cannot cross into the uterus, and thins the endometrial wall so that the uterine environment is more hostile to fertilization and implantation (8,10,11). The estrogen also works to suppress LH levels and prevent ovulation (11).
Progestin-only pills are less widely used than combination pills and are usually reserved for women with medical problems or women experiencing severe side effects from combined pills (8). Like combined pills, progestin-only pills thin the endometrial lining, thicken cervical mucus, and block ovulation, but ovulation may occasionally still occurs (8).
Oral contraceptive pills are very effective at preventing pregnancy. Combined oral contraceptive pills have a failure rate of 0.3% when taken perfectly (correct and consistent use) or a failure rate of 8% when taken typically (10). Progestin-only pills have a slightly higher failure rate because of their inability to fully suppress ovulation (10). However, the failure rate for oral contraceptives can vary greatly if the pills are misused (12).
In addition to preventing pregnancy, oral contraceptives provide many health benefits to women. A study done by the Collaborative Group on Epidemiological Studies of Ovarian Cancer found that women who used oral contraceptives had a reduced risk of developing ovarian cancer for decades after ending use of oral contraceptives (13). Oral contraceptive use also decreases the risk of developing endometrial cancer (10). Additionally, use of oral contraceptives relieves menstrual symptoms in many women by leveling estrogen production, and reduces the amount of bleeding by suppressing growth of the endometrial wall (8).
A third form of the oral contraceptive pill is emergency contraception, commonly known as the “morning-after pill.” Emergency contraception is similar to the daily oral contraception pill but contains a significantly higher dose of hormones (8). Thus, emergency contraception inhibits or delays the natural surge of LH that precedes ovulation (9). However, if emergency contraception is used after ovulation, it is ineffective. Emergency contraception has been a controversial issue in the twenty-first century as politicians have argued over who should be able to buy and use emergency contraception (14-16). In a move to increase access to emergency contraception, in 2013, the FDA approved Plan B One-Step, a form of emergency contraception, to be sold over the counter to all individuals aged 15 and older without a prescription (15).
Not all hormonal contraceptives are oral. Many women cannot adhere to the rigorous daily regimen of pills, so they turn to other forms of hormonal contraception. Many hormonal contraceptives act as the pills do, releasing daily doses of progestin and estrogen, but exist in different physical forms (10). These hormonal contraceptives include patches worn on the skin, rings placed in the vagina, implants that release hormones, and periodic hormonal injections (8).
However, the most effective contraceptive device is the intrauterine device (IUD). The IUD is a device placed in the uterus to change the uterine environment and make it more hostile to fertilization (2,8). IUDs release either the hormone progestin or copper ions to reduce the motility and viability of sperm in order to prevent fertilization (2,10). Once in place, the IUD is an almost 100% effective contraceptive for five years (10).
Non-Hormonal Contraceptives
While hormonal contraceptives block the ability of sperm to reach the egg by altering hormones levels to change the environment of the female reproductive tract, non-hormonal contraceptives physically bar the passage of sperm to the egg. Of the non-hormonal contraceptives, the condom is the most widely used (2). Both male and female condoms exist, the male condom acting as a sheath, and the female condom acting as a pouch (2). Male condoms have a higher success rate than female condoms, and both types protect against the transmission of sexually transmitted diseases (10).
Females also have the option of using diaphragms or cervical caps as a contraceptive. Like condoms, diaphragms and caps are also barriers that prevent sperm from entering the cervix. However, to be most effective, diaphragms and caps must be coated with spermicide before insertion (2). Spermicides contain a detergent that inhibits sperm mobility and ultimately kills the sperm (2). However, the detergent can damage the vaginal wall, which then facilitates transmission of HIV between partners (10). Thus, although they are as effective as condoms at preventing pregnancy, diaphragms and cervical caps are not as popular (2).
Future Contraceptives
The vast majority of the contraceptive options explored above exist for female use. In fact, the male condom is currently the only non-permanent male contraceptive option, but research into alternatives has yielded some promising results. In 2012, Martin Matzuk et al. developed a small molecule that inhibits the ability of sperm to mature as they move through the male reproductive tract (17). The molecule targets a protein in the testes that is needed for proper development and motility of sperm cells. When the molecule was injected into mice, Matzuk et al. found that the mice developed smaller testes, fewer sperm, and sperm with poorer motility. Matzuk et al. also discovered that upon stopping injections, the mice returned to original testes size and normal sperm function (17). Due to the overlap between mouse and human genes, the small molecule holds great potential as a future contraceptive for human males.
Another potential male contraceptive acts via a mechanism similar to the female oral contraceptive pill: by releasing progestin. In 2003, Leo Turner et al. studied the effects of administering testosterone plus progestin to males as a form of contraception. Turner et al. discovered that men receiving the hormonal combination developed fewer sperm and had a higher contraceptive success rate than men who used condoms (18). In 2009, Vahid Mahabadi et al. expanded on Turner’s research and tested a gel containing nestorone, a type of progestin, and testosterone. Mahabadi et al. found that the gel safely suppressed gonadotropins, or sex hormones, so the gel has the potential to also suppress sperm development (19).
A third approach to male contraceptives centers on the use of ultrasound treatment to block sperm production. In 2012, Catherine VandeVoort and Theodore Tollner investigated the contraceptive effects of ultrasound treatment in the rhesus monkey. VandeVoort and Tollner used ultrasound on the monkeys’ scrotums and measured the quality of the monkeys’ semen over time. VandeVoort and Tollner observed that the monkeys undergoing the ultrasound treatment developed sperm with less motility, due to misshaped flagella, and lower overall sperm count (20). Applied to humans, ultrasound treatment could be a successful, easy-to-use, non-hormonal contraceptive.
Conclusion
For individuals currently not interested in having children, contraceptives are an important protective measure to consider. Hormonal contraceptives have a higher rate of preventing pregnancy when taken as instructed than do non-hormonal contraceptives, but they do not protect against sexually transmitted diseases. Additionally, hormonal contraceptives have only been developed for women, placing the burden of contraception solely on the female partners. Ongoing research into male contraceptives has revealed several promising options for the future of contraception. The United States recently celebrated the 50th anniversary of female hormonal contraception – in another fifty years, perhaps both sexes will have a form of contraception to celebrate.
Contact Kristen Flint at
kristen.l.flint.14@dartmouth.edu
References
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