Use of Medroxyprogesterone Acetate Injectable Suspension, USP reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD) as bone metabolism accommodates to a lower estrogen level. This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if use of Medroxyprogesterone Acetate Injectable Suspension, USP by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. In both adults and adolescents, the decrease in BMD appears to be at least partially reversible after Medroxyprogesterone Acetate Injectable Suspension, USP is discontinued and ovarian estrogen production increases. A study to assess the reversibility of loss of BMD in adolescents is ongoing.

Medroxyprogesterone Acetate Injectable Suspension, USP should be used as a long-term birth control method (e.g. longer than 2 years) only if other birth control methods are inadequate. BMD should be evaluated when a woman needs to continue to use Medroxyprogesterone Acetate Injectable Suspension, USP long term. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity.

Other birth control methods should be considered in the risk/benefit analysis for the use of Medroxyprogesterone Acetate Injectable Suspension, USP in women with osteoporosis risk factors. Medroxyprogesterone Acetate Injectable Suspension, USP can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids). Although there are no studies addressing whether calcium and Vitamin D may lessen BMD loss in women using Medroxyprogesterone Acetate Injectable Suspension, USP, all patients should have adequate calcium and Vitamin D intake.

### BMD Changes in Adult Women

In a controlled, clinical study, adult women using Medroxyprogesterone Acetate Injectable Suspension, USP for up to 5 years showed spine and hip BMD mean decreases of 5–6%, compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the first two years of use, with smaller declines in subsequent years. Mean changes in lumbar spine BMD of -2.86%, -4.11%, -4.89%, -4.93% and -5.38% after 1, 2, 3, 4, and 5 years, respectively, were observed. Mean decreases in BMD of the total hip and femoral neck were similar.

After stopping use of Medroxyprogesterone Acetate Injectable Suspension, USP (150 mg), there was partial recovery of BMD toward baseline values during the 2-year post-therapy period. Longer duration of treatment was associated with less complete recovery during this 2-year period following the last injection. Table 2 shows the extent of recovery of BMD for women who completed 5 years of treatment.

### BMD Changes in Adolescent Females (12–18 years of age)

Preliminary results from an ongoing, open-label, self-selected, non-randomized clinical study of adolescent females (12–18 years) also showed that Medroxyprogesterone Acetate Injectable Suspension, USP use was associated with a significant decline in BMD from baseline (Table 3). In general, adolescents increase bone density during the period of growth following menarche, as seen in the untreated cohort. However, the two cohorts were not matched at baseline for age, gynecologic age, race, BMD and other factors that influence the rate of acquisition of bone mineral density, with the result that they differed with respect to these demographic factors.

Preliminary data from the small number of adolescents participating in the 2-year post-use observation period demonstrated partial recovery of BMD.