The FDA approval journey of medroxyprogesterone acetate DMPA, marketed under the brand name Depo Provera, represents one of the most contentious medical regulatory battles in U.S. history, spanning from the 1960s to 1992.
While initially approved by the FDA in 1959 for treating conditions like irregular uterine bleeding, its path to contraceptive approval involved three major FDA rejections in 1974, 1978, and 1983, with concerns ranging from potential cancer risks to ethical questions about clinical trials conducted primarily on vulnerable populations in developing countries without proper informed consent.
Controversial Clinical Trials and Initial FDA Rejections
Testing of Depo Provera as a contraceptive began in the mid-1960s when Upjohn Company initiated human clinical trials that quickly drew criticism for targeting vulnerable populations, including low-income women, women in developing countries, and those with limited access to alternative family planning methods.
These trials raised serious ethical concerns as researchers often failed to obtain proper informed consent, with reports of inadequate record-keeping, lost patient files, and failure to track serious side effects, making meaningful follow-up studies nearly impossible.
The three major rejections reflecting the FDA’s safety concerns include:
- 1974 Rejection: Cited potential cancer risks and questions about long-term safety
- 1978 Rejection: Followed disturbing results from a beagle study where animals developed malignant tumors
- 1983 Rejection: Came after an unusual “Public Board of Inquiry” where gender and power dynamics played central roles
Throughout this process, advocacy groups like the National Women’s Health Network strongly opposed approval based on concerns about study objectivity and potential health impacts on women.
FDA Approval of Depo Provera as a Contraceptive Injection
Despite persistent opposition from women’s health advocates, the FDA finally approved Depo Provera as a contraceptive in October 1992, expanding the range of available hormonal contraceptives in the United States while acknowledging potential side effects like bone mineral density loss and menstrual irregularities.
The approval came after the World Health Organization presented a review to the FDA involving the drug’s use in four developing countries, though critics noted the WHO had already been distributing the drug internationally for years, raising questions about conflicts of interest in the approval process.
The Depo Provera story didn’t end with the 1992 approval, as subsequent innovations led to the development and 2004 FDA approval of Depo subQ Provera, a formulation using a smaller needle and lower dose (104 mg compared to 150 mg) administered subcutaneously rather than intramuscularly.
While these injections remain among the most effective reversible contraceptive options, with failure rates of only about 0.3% when administered on schedule, ongoing concerns about long-term health impacts have led to recommendations limiting continuous use to no more than two years unless other contraceptive methods are inadequate.
