The major complaint about injectable hormonal contraceptives, e.g., Depo-Provera (DMPA), is changes in menstrual patterns. In fact, menstrual alterations are the leading reasons women opt to discontinue their use. Injectables' ability to suppress ovulation over a long period and to cause extended endometrial atrophy can delay a return to fertility. Prior to 1967, clinicians used DMPA to treat endometrial cancer. In 1967, its manufacture, Upjohn, requested the Food and Drug Administration's (FDA) permission to expand its use as a contraceptive. FDA wanted more clinical data because it was concerned about its effect on future fertility. It also requested animal studies on DMPA's effect on bone deposition and cancer risk. By 1978, there was so much evidence of increase risk of cervical and breast cancer in animal models and of birth defects that FDA decided not to approve DMPA. Upjohn had exhausted all options by 1986. WHO clinical research (conducted in Kenya, Mexico, and Thailand) revealed in 1991 that DMPA was not a carcinogen. In fact, DMPA users had a significantly lower risk of endometrial cancer than women who did not use DMPA. Clinical research in Thailand suggested that DMPA causes an increased risk of low birth weight and neonatal mortality. A case-control study in New Zealand indicated that DMPA users experienced more bond density loss than non-DMPA users. Nevertheless, FDA approved DMPA as a contraceptive in October 1992. It did order Upjohn to do a postmarket study of DMPA's effect on bone density and risk of osteoporosis, however. Despite its approval, the controversies would continue until further research provided more details about cancer and other risks. Before January 1993, Upjohn sold vials of DMPA to clinicians at $11 to $12 per injection. After January 1993, it began selling it in single-dose disposable syringes at a cost of $29.50. When the cost of a clinic visit is added, the cost per DMPA injection increases to about $50 ($200/year).