CONTENTS
Chapters
- Research and Regulatory Approval
- Use of Injectables
- Effectiveness and Reversibility
- Side Effects and Complications
- More Evidence in the Cancer Debate
- Noncontraceptive Health Benefits
- Counseling Issues
- Communicating with the Public
- Maximizing Access and Quality
Published with this issue:
HIGHLIGHTS
Published by the Population Information Program, Center for Communication
Programs, The Johns Hopkins School of Public Health, 111 Market Place, Suite 310, Baltimore, Maryland
21202-4012, USA
Volume XXIII, Number 2
August 1995 |
Research and Regulatory Approval
Three events signal a new era for injectable contraceptives:
- A multinational epidemiological study by the World Health Organization (WHO) produced largely reassuring findings about the 3-month injectable depot medroxyprogesterone acetate (DMPA) and cancer. Previous controversy about DMPA had arisen from animal studies.
- The United States Food and Drug Administration (US FDA) approved DMPA as a contraceptive in 1992, 25 years after the manufacturer, the Upjohn Company, first applied. As a result, the United States Agency for International Development (USAID) has begun providing DMPA to developing countries; and
- Two new monthly injectables, Cyclofem™ and Mesigyna™, are
being introduced after thorough clinical studies by WHO (see Chapter
1.4 Monthly Injectables).
Together, these events may clear away some of the constraints that have limited widespread use of this 30-year-old method to a few countries.
Research on injectable contraceptives began shortly after
the development of oral contraceptives. Karl Junkmann and
colleague at the German pharmaceutical firm Schering AG
synthesized the first injectable progestins in 1953 (64, 149) and
in 1957 developed norethindrone enanthate (NET EN, or
Noristerat®), the first injectable contraceptive, which is
injected every two months (150). The US pharmaceutical firm the
Upjohn Company synthesized medroxyprogesterone acetate (Provera®)
in the late 1950s (17). Upjohn conducted the first clinical
trials of Provera in its depot, or injectable,
form—Depo-Provera®—in 1963 (313, 321). Researchers developed the
first monthly injectables and conducted clinical trials in the
1960s. The combination of progestin and estrogen that became
Cyclofem was first tested in 1968, and the combination that
became Mesigyna was first tested in 1974 (223).
US Regulatory History of DMPA
DMPA has always been the most widely used injectable, but
the long wait for approval in the US has made it controversial.
Upjohn applied for US FDA approval in 1967. At the time
progestin-only methods seemed promising because the estrogen in
combined oral contraceptives (OCs) caused nausea and vomiting in
some women. Researchers suspected as well that estrogen caused
blood clots (thromboembolic disease) in some users of combined
OCs. These suspicions were later confirmed. Also, progestin-only
contraceptive injections fulfilled many of the goals of
researchers and family planning providers who wanted to be able
to offer a method that was effective, reversible, did not
interfere with lactation or require action at the time of sexual
relations, and could be easily delivered by rural health care
providers.
Nevertheless, the US FDA denied approval of DMPA in 1978,
saying that it lacked sufficient evidence demonstrating safety,
particularly with regard to breast and cervical cancer (35). A
3-member expert review panel, convened in 1983 at Upjohn's
request, upheld the US FDA decision (322). |
