Depo-Provera was approved for use as a contraceptive by Health Canada in April,
1997 after several previous applications by the manufacturer had been denied.
Canada now joins over 90 other countries where Depo-Provera is approved, including
the U.S.
A synthetic form of the hormone progesterone, Depo-Provera is a very effective
contraceptive when given to a woman by injection every three months. For the
past 20 years, it has also been the subject of much debate and controversy
in Canada and internationally about its risks and benefits to women's
health and about many of the circumstances of how the drug has been tested
and used.
Many women's health and community agencies, including Women's
Health Clinic, international development organizations and others have monitored
this issue for almost two decades and opposed formal approval of Depo-Provera
for contraceptive use. As part of the Canadian Coalition on Depo-Provera, Women's
Health Clinic took that position largely because of concerns about specific
health risks, because of what is still not known about the drug, and to highlight
the potential social misuses of Depo-Provera. We urged the federal government
to establish a registry of women given the drug.
Prior to its approval, Canadian doctors could prescribe Depo-Provera as a
contraceptive because it was approved in Canada for other uses - endometriosis
and the palliative treatment of certain cancers - but the manufacturer could
not advertise the drug as a contraceptive. (This is true for other drugs that
are known to be effective but do not have formal approval for particular indications.)
With Depo-Provera now marketed as a contraceptive, more doctors may consider
prescribing it; more ads are directed to women consumers (many ads already
reach Canada through U.S. women's and teen magazines although prescription
drugs are only supposed to be advertised to doctors), and the manufacturer,
Upjohn-Pharmacia, gains additional credibility in Canada and internationally.
Approval is also healthy for sales and profits.
Since many concerns regarding its use were not addressed prior to approval,
it is timely to assess what is known about the drug's risks and benefits. Was
there any new information upon which Health Canada may have based its approval?
What lessons have we learned following this issue over the years? How can we
apply this knowledge to improve the delivery of quality reproductive health
care for women, especially young women who in Canada are a particular target
group for Depo-Provera?
Bringing Depo-Provera Home: A Partial History
In 1981, a delegation of Canadian women attended the 2nd International Conference
on Women's Health in Geneva. We met with health providers and activists from
India, Bangladesh, Thailand and Latin America, many of whom were highly critical
about the use of Depo-Provera in population control programs and in clinical
trials in their countries. Accurate information about the drug was scarce;
many women thought it was approved in the U.S. and Canada at that time (it
wasn't) and serious questions were raised about its use in settings such as
refugee camps, where women had no choice but to receive "the shot," often
with no explanation. In this heavy-handed approach, contraceptives were seen
as the key to population control.
There is now greater formal recognition by the U.N. and international agencies
that birth rates fall when women's education and status are improved
and that contraceptives must be available along with a good system of primary
health care, social supports and health education. However, governments rarely
allocate sufficient resources to make this a reality.
Third world delegates at the conference asked us to send them hard-to-find
research data on Depo-Provera, and to ensure that the drug was carefully reviewed
by our regulatory bodies if it was approved. Many of us gathered extensive
files over the next five years which we shared.
In November 1985, after a Food and Drug Administration public inquiry panel
denied approval of Depo-Provera for contraceptive use in the U.S., citing concerns
about long-term safety, the Globe and Mail reported that the drug was about
to be approved in Canada. An Upjohn spokesperson was quoted saying that Depo-Provera
won't be opposed here like in the U.S. “We do things in a more
private way in Canada... Here it is a matter between us and Health and Welfare.” Approval
in Canada would have been strategic for the company at a time of U.S. refusal
and as a possible site of export.
The issue had come home. Concerned health providers, consumers, women's
health, disability and international development NGOs formed the Canadian Coalition
on Depo-Provera to demand: public hearings into long term safety issues; more
research in Canada and internationally on women's experiences with Depo-Provera;
and that submissions by marketing companies be made public and marketing practices
reviewed.
The federal government eventually agreed to closed hearings in 5 cities across
Canada in 1986. Scores of groups and individuals presented briefs. Some supported
approval, but many addressed concerns about the range of the drug's side
effects, possible long-term risks to women's health, and documented cases
of use of the drug in Canada without adequate informed consent, particularly
by women with disabilities in Ontario institutions, immigrant and refugee women,
and Aboriginal women, including many teens. Health Canada did not approve Depo-Provera
for contraceptive use then nor in a subsequent appeal in 1992 (after the U.S.
finally approved it), noting there were unresolved long term health risks for
Canadian women.
The most prominent research studies have focused on Depo-Provera and breast
cancer, based on women from 5 sites in Kenya, Thailand and Mexico (WHO, 1991)
and from New Zealand (Paul et al, 1989), with a recent analysis pooling the
data from these (Skegg et al, 1995). A small study in New Zealand also looked
at the effects of Depo-Provera on bone density (Cundy et al, 1991; 1993). While
some of the data appear reassuring, other findings remain unclear or inadequately
researched. Many concerns remain. We do not know the specific reasons for Health
Canada's decision to approve the drug.
Lessons Learned
From these experiences, we have learned a good deal about what is known and
not known about Depo-Provera, about how scientific research may fail to ask
relevant questions, how the global pharmaceutical industry works, the politics
of drug approval in Canada and internationally, and about the hard decisions
health care providers and clients must make when confronted with complex life
situations. For example, we've learned that:
- Critiques of research must be scientifically accurate and credible, based
on a sound understanding of methods appropriate to the problem. If your facts
are wrong, you lose credibility with health professionals, researchers and
government. If you have been scrupulous in your work, you can often identify
critiques others have missed. The Coalition uses independent epidemiologists
to help interpret research findings.
- It is frustrating, but essential, to try to understand how the Canadian
drug approval process works. Closed to public accountability, consumers have
no way of finding out the basis on which drugs are considered or approved,
except by the lengthy process of applying for documents through the Access
to Information Act (The Coalition did this in 1986; another group is seeking
information on the current approval). A powerful lobby by the Pharmaceutical
Manufacturers' Association of Canada helps ensure close collaboration
between industry and government. Increasing privatisation of the drug review
process raises further concerns.
- As a new reproductive technology administered by a health care provider,
Depo-Provera highlights complex social issues in clinical practice. Because
Depo doesn't require daily client action, it is often considered convenient
for women who do not/cannot remember to take pills or other client-controlled
methods; for women who have had unplanned pregnancies and/or abortions, sometimes
as a result of contraceptive failures and who want a highly effective method;
for women who don't want their partner to know they are on birth control,
for example, women in abusive relationships, subject to coercive sex; women
for whom pregnancy presents high risks, such as those struggling with alcohol
or solvent abuse. These are complex life situations, in which health providers
must help women weigh the risks and difficulties of pregnancy to those of using
Depo.
Depo-Provera may help “buy time” for women in difficult situations,
but it is not the quick fix solution. Social and other supports are needed
to address the often underlying issues of poverty, abuse, and low self-esteem.
As well, some providers too readily assume a woman will be “non-compliant” in
taking other forms of birth control. Immigrant, refugee and Aboriginal women
have complained about providers offering them Depo-Provera as a first choice
contraceptive, not taking time to discuss other alternatives and discouraging
them from having more children. All clients, but particularly women marginalized
in the health care system, need time and sensitive counselling to ensure informed
choice. Since Depo has the potential to be misused and its effects remain in
the body beyond three months, it should not be a first-choice contraceptive,
but considered only after all other alternatives are explored.
The Next Steps:
Guildelines and Protocols
Given these social concerns and the limitations of the research on Depo-Provera
(See Box 2), many health providers and consumers would like to see clearer
guidelines and protocols for contraceptive counselling and use that are specific
to the situations and health status of Canadian women. For example:
- Since Depo-Provera reduces estrogen needed to build healthy bone mass in
young women, particular care should be taken prescribing Depo-Provera to young
women. Women preoccupied with weight and dieting or who have eating disorders
already tend to have lower levels of estrogen. Canadian women have high rates
of osteoporosis; the risk of contributing to such a trend should be an issue
of concern.
- Depo-Provera has a mild, but definite effect on insulin levels. It is suggested
that women with diabetes, or a tendency to diabetes, should be closely followed
if taking Depo. This is a significant issue for Aboriginal women in Canada
who have high rates of diabetes, who as a population do not generally have
good access to health care services, and to whom Depo-Provera is often given.
- While the data on Depo and breast cancer is more reassuring for longer term
users, there is a significant, unexplained risk for younger women who were
recent users of Depo and took it for a short period of time. In particular,
young women considering Depo should be asked about risk factors for breast
cancer, but health care providers and clients must recognize that young women
cannot easily be screened or monitored for breast cancer through mammography
or breast self exam.
- Depo-Provera, like the pill and other hormonal contraceptives, doesn't
protect against sexually transmitted diseases or HIV, and may even facilitate
HIV transmission. For increasing numbers of young women, STDs will cause infertility
and other problems in later years.
Because of its ease of use, Depo-Provera doesn't require a couple to
think about contraception in relation to sex, in contrast, say to barrier methods,
or the pill which encourages more self-awareness, responsibiltiy and forethought
for women. It may be difficult to encourage safer sex practices and use of
condoms with Depo-Provera or other methods that are controlled by providers,
especially for very young women, and others who find it hard to negotiate with
male partners. This is not unique to Depo-Provera, but is an issue that health
care providers must address, given increasing rates of STDs and HIV.
Registry and Research
There is a need for a registry for Depo-Provera users for research and so women
could be notified if future concerns arise. Population health studies are
also needed on the use of Depo-Provera in relation to conditions such as
diabetes, heart disease, its effects post abortion, and post partum, about
which little is known; and for qualitative research on the social issues
and contexts of Depo's use as a contraceptive. Knowing to whom it is
given, under what circumstances and with what outcomes may lead to a deeper
understanding of how to assess social risks, and identify ways clients in
difficult situations can be helped to address the roots of the problems they
are facing.
There must be new opportunities for health care providers and consumers to
work together to develop models of care that empower women /couples to make
appropriate, safer contraceptive choices, and achieve healthy, satisfying relationships,
free of coercion of any kind.
With Depo-Provera approved, the hard work lies ahead.
|
Research on Depo-Provera: A few concerns...
* Much of the research is based on studies of women with very different health
and disease profiles (e.g. rates of breast cancer, osteoporosis, diabetes,
heart disease, etc) and lifestyles, diets, other environmental factors and
genetics, from Canadian women.
* Two studies, one by the World Health Organization (WHO, 1991) and one in
New Zealand (Paul et al, 1989) showed increased risk of breast cancer among
current and recent users of Depo-Provera, but that risk did not increase with
prolonged use. The risk of breast cancer appeared to be increased in women
diagnosed at younger than 35, and in women who had used Depo before age 25.
Both groups of researchers suggested that Depo-Provera may promote the development
of new tumours or accelerate preexisting ones. Because younger women have dense
breast tissue, screening methods like mammography are not effective in monitoring
breast changes.
* A prospective study of sex trade workers in Thailand found higher HIV seroconversion
rates among women using Depo-Provera. The researchers speculate whether the
thinning of the vaginal epithelium may create small tears and facilitate the
transmission of HIV (Ungchusak et al, 1996).
* Research in New Zealand showed that 30 women on Depo-Provera had lower bone
mass than other women of the same age, but that this effect was reversible
when Depo-Provera was discontinued. (Cundy, 1991; 1993) A pilot study showed
a decrease in bone mass among adoloscents on Depo-Provera, while a control
group had increasing bone mass (Blair et al, 1995). Two large-scale prospective
studies currently underway do not include women under age 18. Upjohn is supposed
to have completed a 7 year prospective study on bone density involving 450
women, ages 25-35; as yet there is no report.
* Depo-Provera affects insulin response, but there is little research on the
implications for diabetes, especially in high risk populations.
* Virtually no research has been done on the impacts of Depo-Provera on the
risk factors for heart disease and stroke.
* We don't know much about the impacts of Depo-Provera on a woman's
post partum or post abortion hormonal state. The drug is often administered
at these times.
Some Facts About Depo-Provera
Depo-Provera is an injectable contraceptive, effective when administered every
3 months in doses of 150 mg. It blocks hormonal signals from the hypothalamus
and pituitary gland near the brain necessary for ovulation; thickens cervical
mucus, making it difficult for sperm to pass through and fertilize an egg;
and thins the lining of the uterus, reducing chances for conception and implantation.
For every 100 women taking Depo-Provera at correct intervals for one year,
less than one will become pregnant.
* Synthetic progesterone-only contraceptives (progestins) like Depo-Provera
may be an appropriate option for women who cannot take estrogen-based contraceptives;
who take anti-seizure medication; or who have sickle cell disease.
* Studies suggest Depo-Provera is protective against endometrial cancer and
may protect against ovarian and cervical cancer and pelvic inflammatory disease.
More research is needed.
Side Effects
Most women using Depo-Provera experience menstrual irregularities such as
irregular bleeding or spotting, and for some, heavy bleeding. Amenorrhea (an
absence of periods) commonly develops any time during the first year. This
may make early detection of pregnancy difficult, while other women may worry
unnecessarily that they might be pregnant. Fetal development may be affected
by exposure to Depo-Provera. Menstrual irregularities may also mask the onset
of menopause.
Weight gain affects most women, averaging about 2.3 kg (5 lbs) in the first
year and varying after that; some women gain significantly more. The reasons
are unclear, but it may be that by suppressing estrogen, there is a higher
ratio of androgenic (male) hormones, muscle growth and increased appetite.
Other side effects may include: acne, breast tenderness, headaches, nervousness,
depression and loss of libido. The delay in return to fertility averages 3-6
months, but may be up to 18 months or more for a small number of women. Symptoms
may persist 6-8 months or longer after the drug is discontinued.
Anyone with blood-clotting problems, unexplained vaginal bleeding or other
conditions should discuss these with their health care provider before considering
Depo-Provera or other methods.
Depo-Provera does not protect against STDs or HIV. Condom use is recommended.
Sources: CPS, 1997; R. Hatcher et al., Contraceptive Technology, 1994. |
Fall, 1997.
Prepared by Sari Tudiver, Ph.D., Resource Coordinator, Women's Health
Clinic, Winnipeg, Manitoba, Canada. With special thanks to: WHC staff Carolyn
Clarke, N.P., Catherine Wilkie, M.D., Carol Scurfield, M.D., Gio Guzzi, Coordinator,
Birth Control and Unplanned Pregnancy Program; Madeline Boscoe, R.N., Advocacy
Coordinator, and to Patricia Kaufert, Ph.D., Department of Community Health
Sciences, University of Manitoba.
Originally published in Women's Health Clinic newsletter, 1997
