Science / Medicine : Beyond ‘The Pill’: New Birth Control Devices Are Still Long Way Off
In a society that fairly reeks of technological advances, birth control seems stuck in the ‘60s. On the surface, it appears the contraceptive revolution that ushered in the birth control pill has come to a screeching halt. For almost three decades, women and men have had to be content with the same limited choices.
Can we hope for more options in the immediate future? “Don’t hold your breath,” responds pharmacologist Gabriel Bialy, chief of the contraceptive development branch at the National Institute of Child Health and Human Development.
But while the picture is bleak for the consumer searching the pharmacy shelves, a look behind laboratory doors reveals that long-term prospects are a bit brighter. The small group of scientists is investigating a full arrat of potential contraceptives, all at various stages of development.
Most of these products rely on the basic building blocks of the oral contraceptive, estrogen and progestin. These steroid hormones are released in a cyclic fashion naturally by the ovaries. In birth control pills, the continuous flow of hormones inhibits ovulation through a feedback loop operation.
While scientists capitalized on this manipulation of hormones to develop the pill, today they have expanded beyond the one-a-day concept, packing the hormones into an variety of alternative delivery systems. Researchers hope eventually to offer implants, injectables and vaginal rings. All of these techniques release steroid hormones in a slow and steady dose over various lengths of time.
Norplant, one of the most promising methods, is now available in 15 countries outside the United States--including Finland, Sweden and Czechoslovakia--and will soon complete clinical trials in the United States. The device consists of six match-stick size capsules, filled with the progestin levonorgestrel and inserted with a tiny incision under a woman’s arm.
After the simple, 15-minute procedure, the woman remains protected from pregnancy for five years. If for any reason, she wishes to discontinue use, a practitioner can remove the capsules.
Unlike the birth control pill, Norplant and many of the other long-acting contraceptives contain a single hormone, progestin. Working alone, without the accompanying estrogen, progestin will still inhibit ovulation by blocking gonadotropin releasing hormone(GnRH). The hormone also causes thickening of the cervical mucus, which prevents fertilization.
Dr. David Archer, clinical investigator in the Contraceptive Research and Development Program (CONRAD) at Eastern Virginia Medical School, says scientists excluded estrogen from the formulation to eliminate the cardiovascular and blood clotting risks of the birth control pill. However, this non-estrogen package comes with its own trade-offs. The single-steroid contraceptives cause abnormal bleeding in many women during the first year. Some spot continuously throughout their cycle, while others lose their periods altogether.
According to some, this annoying side effect may place a damper on the marketing potential of progestin-only contraceptives. Dr. Daniel Mishell, chairman of the department of obstetrics and gynecology at Los Angeles County, University of Southern California Medical Center, has been running Norplant clinical trials. He predicts Norplant won’t ever achieve the pill’s popularity in the United States because unpredictable bleeding patterns will scare away potential users.
A few variations on the implant theme are also under scrutiny. Scientists at Family Health International in North Carolina have created an injectable formulation in which the progestin norethindrone is encased in tiny, biodegradable microspheres. Over a 9O-day period the smallest spheres dissolve first, releasing hormone into the blood stream, with the larger ones progressively disintegrating over time.
For those wary of needles or incisions, researchers have an additional hormone-based option up their sleeves. The flexible, doughnut-shaped, vaginal ring can be formulated with both estrogen and progestin. Women place the one size-fits-all ring on the cervix like a diaphragm. This localized form of birth control pill remains in place for three weeks and is then removed during the menstrual cycle. The hormone supply lasts four to six months.
Mishell speaks optimistically about the ring. The hormones enter the bloodstream directly by diffusing through the vaginal wall. This allows for a low, even infusion of drug, as opposed to the peaks and valleys associated with oral medications. One key advantage: women who have used the ring say they don’t experience any of the nausea common to the pill.
USC plans to begin large, “phase three” trials of soon to establish whether or not the vaginal ring works. Mishell says that of the approximately 70 women participating in the study over the last few years, no one has ovulated.
Taking a different tack from the steroid approach, some research groups are pursuing vaccines and other methods of specifically blocking sex-related hormones.
At CONRAD, scientists have been investigating two avenues. They are attempting to develop vaccines that would inhibit sperm from attaching to the egg. The researchers also plan to construct agents that block gonadotropin-releasing hormone, the choreographer of ovarian and testicular hormone release.
Scientists hope to develop an antagonist to GnRH and suppress GnRH activity. Without the stimulus of GnRH, ovulation and sperm production would be inhibited.
However, by turning off the GnRH faucet, scientists block a repertoire of other essential functions, including the release of estrogen, progestin and testosterone. Men would no longer need to shave; they would also loose their libido. Women could experience vaginal dryness along with a potential decrease in sex drive. According to Archer, if such a compound were marketed, both men and women would need to take supplemental hormones.
Archer’s group, also working in vaccine research, has identified a unique protein, called ZP3, which protrudes from the oocyte, the developing egg. ZP3 represents one of the many protein receptors to which sperm bind during fertilization.
Scientists aim to develop a vaccine that would stimulate the body to produce an antibody against the ZP3 protein. The compound would cap the protein, effectively shielding the sperm binding site and preventing fertilization.
But what if a woman decides after being vaccinated that she wants to become pregnant? How reversible would this process be? Archer’s group is struggling with this issue, and in animal studies thus far they’ve found immunization against ZP3 wears off in a short period of time. For a woman wanting to become pregnant, that’s good news. On the other hand, those who desire long-term protection would need regular booster shots. For this reason, researchers hope to identify other proteins that could impart permanent immunity, producing, in effect, sterilization.
When can we expect to see any of these new methods offered to the public? No one knows for sure, but many are willing to speculate. According to the Population Council, the nonprofit Norplant should be approved by the Food and Drug Administration this year. Thereafter, it will require a few more years before the logistics are in place for marketing.
It is certain that vaccines won’t be appearing in the immediate future. Opinions diverge greatly: Mishell states, “I don’t think they will ever be used in humans because the response is too variable,” while Archer optimistically predicts their arrival around the year 2000.
Then there is the question of public acceptance. Bialy isn’t willing to place any bets on that, but he says, “The field is not standing still. Research is ongoing. But the . . . the immediate horizon is still very, very foggy.”
HOW BIRTH CONTROL WORKS
Under normal circumstances, the hypothalamus conducts a complex symphony of hormones, orchestrating first the release of gonadotropin releasing hormone(GnRH). This signals the pituitary to secrete luteinizing hormone (LH), which in turn facilitates ovulation and coordinates release of estrogen and progestin from the ovaries.
In contrast, a woman using a hormone-based birth control method, like the Norplant or vaginal ring, maintains a steady circulation of estrogen and progestin. The hypothalamus senses this constant presence of steroids and shuts off GnRH production in reaction. Without this key player, LH is also inhibited and ovulation ceases to take place.
NORPLANT METHOD
The Norplant, six match-stick-size capsules implanted under the skin, continuously releases a minute dose of progestin, providing pregnancy protection for five years. The progestin blocks the gonadotropin releasing hormone (GnRH) which in turn, inhibits ovulation and causes the cervical mucus to thicken, preventing fertilization.
VACCINE METHODS
Two different types of vaccines under development are designed to block sex-related hormones. One vaccine, which could be used by men and women, contains a “blocker” for GnRH, which inhibits ovulation and sperm production. Another method would be a vaccine to produce an antibody against the protein ZP3, the chemical that helps bind the sperm to the egg.
VAGINAL RING METHOD
Another time-release method is a plastic ring formulated with both estrogen and progestin to inhibit ovulation. The flexible ring, inserted like a diaphragm, remains in place for three weeks and is removed during the menstrual cycle. The hormone supply, which diffuses into the blood stream through the vaginal wall, lasts four to six months.
