DepoProvera®:
A Monthly ContraceptiveIntroduction
It may be the birth control compromise many woman have been
looking for. Falling in between the daily effort of remembering the pill and the
once-every-five-years appointment for the implant, one injection of Depo-Provera
in the muscle of the arm or buttocks protects against pregnancy for three
months.
The Food and Drug Administration approved Depo-Provera, manufactured by The
Upjohn Co., Kalamazoo, Mich., for contraception last October. The active
ingredient in Depo-Provera is a synthetic hormone similar to the natural hormone
progesterone.
"I was not happy with other methods," says Becky Schroder, of Jacksonville,
Fla. "I was a poor pill taker. I forgot. And I thought that barrier methods were
inconvenient and messy."
Schroder, 31, started on Depo-Provera three years ago, when its use as a
contraceptive was still investigational. (FDA had previously approved the drug
for treating endometrial and renal cancers.)
Depo-Provera inhibits the production of another hormone,
gonadotropin, which,
in turn, prevents ovulation. Depo-Provera also causes changes in the lining of
the uterus that make pregnancy less likely to occur.
Depo-Provera's estimated effectiveness in preventing pregnancy is 99 percent,
on a par with Norplant, the contraceptive implant. Norplant contains another
synthetic progestin hormone, levonorgestrel. (See "Norplant: Birth Control at
Arm's Reach" in the May 1991 FDA Consumer.)
Mark Your
Calendar
The amount of Depo-Provera in the bloodstream is at the highest
level just after injection. Over time, the level drops and after three months,
the level may no longer offer enough protection against conception.
"Go back on time for the next injection," says Ridgely Bennett, M.D., the FDA
medical officer responsible for reviewing the new drug application for
Depo-Provera. "That should be made abundantly clear."
He adds that if the time between injections is greater than 14 weeks, the
physician should make sure the woman isn't pregnant before giving her the next
injection.
Getting
Started
A woman should get her first injection of Depo-Provera within five
days after the start of her menstrual period. The drug is effective immediately,
so no other birth control is necessary.
Because Depo-Provera is not a barrier contraceptive, however, it offers no
protection against sexually transmitted diseases such as AIDS, herpes, chlamydia, and gonorrhea. For optimum protection from both disease and
pregnancy, couples may choose to use both Depo-Provera and a condom.
A woman who has just had a baby--and wants to wait before having
another--should get her shot within five days after the birth if she is not
breast-feeding, and six weeks after the baby is born, if she is.
Although numerous studies by the World Health Organization have shown that
Depo-Provera does not have any adverse effects on breast milk production or
composition, or on the health of the nursing infant, it's best not to expose a
newborn to the drug in the first six weeks, according to Philip Corfman, M.D., a
supervisory medical officer in FDA's division of metabolism and endocrine drug
products. "It's just a precaution," he says.
If a woman decides at the end of three months that she wants to get pregnant,
she simply doesn't get the next injection. But, because the length of time
between the last injection and becoming pregnant varies widely, any woman
starting Depo-Provera should be sure she doesn't want to become pregnant for the
next year or two, says Susan Wysocki, executive director of the National
Association of Nurse Practitioners in Reproductive Health.
According to the approved physician's label, "the median time to conception
for those who do conceive is 10 months following the last injection with a range
of four to 31 months." Since Depo-Provera does not accumulate in the body, the
return to fertility is independent of the number of injections received, but may
be affected by a woman's age or weight.
A woman should not take Depo-Provera if she has acute liver disease,
unexplained vaginal bleeding, breast cancer, or blood clots in the legs, lungs
or eyes.
"She also shouldn't have a fear of injections," Wysocki says.
Side
Effects
Change in the menstrual cycle is the most common side effect of
Depo-Provera. At first there may be irregular bleeding or spotting, but that
usually diminishes and eventually disappears after several injections. After a
year on Depo-Provera, menstruation will stop completely in approximately half of
the women.
Normal menstruation will usually return within a few months once the
injections stop.
Women who continue to menstruate while on Depo-Provera may have decreased
blood flow, which, in turn, reduces the chance of anemia. There may also be a
decrease in menstrual cramps and pain, as well as ovulatory pain.
Schroder, who had very painful premenstrual symptoms before starting
Depo-Provera, says she thinks of these side effects as benefits.
After menstrual changes, the most common side effect is weight gain. "It's
not clear whether the weight gain is due to water retention or a metabolic
effect that increases appetite and body fat," says David Grimes, M.D., a
professor with the department of obstetrics and gynecology at the University of
Southern California School of Medicine. "But it is real, and women should know
about it."
In addition, some patients may experience headache, nervousness, abdominal
pain, dizziness, weakness, or fatigue.
Breast
Cancer Concerns
The possibility of a link between Depo-Provera and breast
cancer was first considered in the early 1970s, after breast cancers were found
in beagles treated for more than three years with a dose of Depo-Provera
equivalent to 25 times that of the human contraceptive dose. However, those
studies were eventually discounted at an October 1981 meeting of the World
Health Organization. Experts at that meeting concluded, and FDA later agreed,
that beagles were not appropriate animal models for determining what the
potential effects of Depo-Provera would be on women.
Ten years later, WHO presented the results of a study of over 11,000 women
who used Depo-Provera, mainly in Thailand and New Zealand. (The drug has been
approved for contraception in about 90 countries.) Based on the study, published
in the Oct. 5, 1991, issue of The Lancer, WHO concluded that, overall,
women on Depo-Provera are not at increased risk of breast cancer. In addition,
breast cancer risk did not increase the longer a woman stayed on the injectable
contraceptive.
The study did find a slight increase in the risk of breast cancer during the
first four years of use, primarily in women under 35. That increase, however, is
statistically weak and comparable to the risk associated with oral
contraceptives, according to the researchers.
But the National Women's Health Network disagrees with the researchers'
conclusion. In testimony presented to FDA's Fertility and Maternal Health Drugs
Advisory Committee last June, Cindy Pearson, a representative of the National
Women's Health Network, said that the WHO studies were conducted in countries
with breast cancer rates less than half that of the United States and therefore
can't be accurately applied to women in this country.
She adds that comparing the breast cancer risk to that associated with oral
contraceptives is also misleading. "These disturbing data are emerging from much
smaller groups of women than was the case with oral contraceptives," she said.
"Only three epidemiologic studies have been done on Depo-Provera and breast
cancer, and all three raise a red flag."
However, to Grimes, that increased risk in younger women isn't a link to
Depo-Provera. Instead, "It suggests to me that women who start taking
Depo-Provera may be coming into the health-care system for the first time and
having preexisting tumors discovered."
"It should be noted," says FDA's Bennett, "that more data on breast cancer
risk is now available for Depo-Provera than has been required for any other drug
prior to marketing."
The results of the WHO study also indicated that Depo-Provera use did not
increase the overall risk of cancer of the liver, ovaries, endometrium, or
cervix.
Osteoporosis
Risk?
A study by Tim Cundy and colleagues, published in the July 6, 1991,
issue of the British Medical Journal found that the bone density in 30 women who
had been using Depo-Provera for at least five years was less than the bone
density of other women of similar age. Cundy recommends "that women with more
than one risk factor for osteoporosis [family history, underweight, cigarette
smoking, European or Asian origin] should have bone mineral density measurements
undertaken if they are considering Depo-Provera use on a continuing basis, and
those in the lower third of the normal range are advised to consider other
contraceptive methods."
While FDA's Corfman agrees that a woman considering Depo-Provera needs to
discuss the possibility of bone thinning with her doctor, he adds, "[the risk
of] osteoporosis is just part of the calculation. There are many other issues
involved."
FDA is requiring Upjohn to conduct additional research on the effects of
Depo-Provera on bone density.
Best
Candidates
"[Depo-Provera] has been a godsend for women who've been unable
or unwilling to use other methods," says Grimes.
Becky Schroder's plans to have a baby in the next two or three years made her
decide against Norplant. Although the implant can be removed at any time, "it
isn't cost effective if it's taken out early," she says.
But Pearson, of the National Women's Health Network, is concerned that
Depo-Provera will be forced on poor women. She told FDA's advisory committee
that "the women's health movement has already documented many cases of coercion
even while Depo-Provera was not approved as a contraceptive."
Wysocki acknowledges Pearson's concern. "That concern stems from some very
real things that happened back in the 60s, particularly with sterilization, but
there's no reason to believe that because the technology is available that it
will be abused. The problem itself should be addressed, not the drug."
Wysocki adds that Depo-Provera is a safe, low-cost method of contraception
that requires little attention. "No one method of contraception is perfect for
all women at all times during their reproductive years," she says. "However,
additional options increase the likelihood that a method of contraception that
matches each woman's need will be found."
(For more information on all methods of contraception, see the FDA
Consumer reprint "Comparing Contraceptives." Write to FDA, HFE-88, 5600
Fishers Lane, Rockville, MD 20857, for single copies.)
About the Author
Dori Stehlin is a staff writer for FDA Consumer.
Document Source:
U.S. Department of Health and Human Services
Public
Health Service
Food and Drug Administration
FDA
Consumer
March 1993
[Thanks to Rees AM (ed): Consumer
Health USA. Phoenix, Oryx Press, 1995, pp 83-85. and Medscape's full text
articles and Medline] |
