Almost 50 years ago the combined oral contraceptive pill was approved by the Food and Drug Administration (FDA) for use in preventing pregnancy, ushering in a new era of hormonally-based birth control. Now, in addition to the original “Pill” women can chose from an overwhelming variety of oral contraceptives, from different hormone combinations and doses to different Pill schedules that result in skipping or stopping menstruation entirely. Most of us have heard that the Pill contains hormones that suppress ovulation, but how does this really work? And with the recent marketing of Lybrel — a Pill designed to stop menstrual cycling entirely — we might wonder how far we can reasonably take this hormonal control. Simply put, how does the mechanism of oral contraceptives guide us in their use, and what (if any) are the repercussions of eliminating menstruation?
The story of how the Pill was engineered to suppress ovulation is one of the first examples of researchers using naturally occurring hormones to re-direct normal human biology. As far back as the 1920s, scientists had determined that transplanting ovaries from pregnant rabbits into other fertile rabbits prevented pregnancy, and by the mid-1940s it was known that the hormone Progesterone was responsible for this effect. Researchers then wondered: What is the role of Progesterone and other hormones in regulating normal reproductive biology, and could this knowledge be safely used to suppress ovulation in humans?
How does the Pill work?
Before pills could be formulated to modify human ovulation, researchers needed to figure out how the menstrual cycle usually works. The normal cycle consists of several distinct phases that average approximately 28 days in total; each phase corresponding to physical changes that occur to “build up” and “break down” the uterus in preparation for pregnancy, with ovulation occurring at the midpoint of the cycle. These phases are associated with dramatic changes in the levels of certain hormones that follow carefully scripted roles in promoting ovulation and subsequently (in the absence of fertilization) menstruation.
The shedding of uterine lining leading to the observed bleeding is the Menstrual Phase. As bleeding ends, Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) show small peaks above their normal low levels, leading to thickening of the uterine lining and maturing of oocyte(egg)-containing follicles in the ovary. Meanwhile, the estrogen, Estradiol (E), is steadily rising to a peak a few days before ovulation, after which point FSH and LH spike once more, triggering the release of a mature oocyte. Levels of Progesterone (P) and E rise for the next two weeks, preparing the uterine lining for implantation of an embryo. If no implantation occurs, both hormone levels drop sharply, triggering menstruation. If fertilization and implantation do occur, levels of P and E remain high throughout pregnancy, suppressing the spikes of FSH and LH that drive ovulation.
Because of the intricate feedback loops controlling the menstrual cycle, artificially altering one or two hormones can affect the entire cycle. This fundamental knowledge has been used both to suppress the cycle, with the goal of contraception, as well as to stimulate ovulation with the hopes of promoting fertility. Two ideal targets for hormonal contraception would be the hormones FSH and LH, which play dual roles in the normal menstrual cycle, first re-starting the cycle after menstrual bleeding and then triggering ovulation at the mid-point of the cycle. Because FSH and LH are required to trigger ovulation, artificially blocking these two hormones would therefore robustly suppress ovulation. Why then are the hormones P and E commonly used in the Pill instead? It is generally easier to add something to a biological system than to remove something, and since P and E suppress the release of FSH and LH these are logical choices for halting the sequence of events that lead to ovulation. Because both P and E are at high levels throughout pregnancy, some people describe taking the Pill as “tricking the body into thinking it’s pregnant”. While not entirely accurate, this statement does have some truth to it.
How well does the Pill regimen mimic the normal menstrual cycle?
The standard combined oral contraceptive consists of both hormones P and E, taken daily for three weeks, followed by a week of no pills (or placebo pills) that trigger what’s known as “breakthrough bleeding”, induced by the drop in hormones. Although the outward appearance is the same (menstrual bleeding in week 1 of a 28 day cycle) the constant high levels of P and E for a woman taking the Pill actually abolish the normal hormonal cycling that underlies ovulation. The Pill therefore replaces the normal menstrual cycle with an artificial cycle (3 weeks of “mimicking pregnancy”, followed by 1 week with breakthrough bleeding). Historically, women have been pregnant or nursing much of their adult lives and thereby suppressing ovulation naturally, suggesting that halting menstruation is not inherently harmful. Yet, many women still wonder if it is safe to eliminate menstruation using oral contraceptives.
Actually, women have been using the Pill in this off-label manner under medical supervision since the time it debuted — skipping the week of placebo pills in order to postpone their periods during a vacation or special event, for example. Continuous menstrual suppression via the Pill has also been used to treat endometriosis, debilitating menstrual pains and other menstruation-related ailments. However, it is only recently that certain formulations of the Pill began to be marketed for the specific purpose of eliminating periods. The first widely available Pill of this nature was Seasonale, FDA approved in 2003. Each packet of Seasonale contains 84 Pills and 7 placebos, resulting in 4 periods per year. In 2007, the Pill, Lybrel, was introduced, eliminating the placebos entirely with the goal of suppressing menstruation as long as the Pill is taken. So, although at first glance it may seem unusual to provide an oral contraceptive regimen that eliminates periods, the use of Seasonale, Lybrel and other similar formulations is a logical progression from the original concepts behind the Pill. These new formulations contain the same types and amounts of hormones as the standard Pills, so should be comparable in terms of side effects (both immediate and potentially long-term). However, the lack of menstruation does mean that a woman who becomes pregnant on this regimen may not realize it as soon as she otherwise would. How popular this newly-advertised birth control regimen will be (given that it removes the visible monthly proof of its efficacy) remains to be seen.
–Amanda Nottke, Harvard Medical School
For More Information:
Information regarding the FDA’s approval of the prescription drug, Lybrel:
< http://www.fda.gov/bbs/topics/NEWS/2007/NEW01637.html >
Science Daily article about menstruation suppression using oral contraceptives:
< http://www.sciencedaily.com/releases/2007/10/071003140446.htm >
“A Short History of Oral Contraception” Wolfgang Oelkers, The Endocrinologist, Issue 80, p.15.