Differential effects on bone density of progestogen-only methods for contraception in premenopausal women

Abstract

The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed. Data from a prospective randomized clinical trial among 22 premenopausal women, age 32.6 (range 20-45 years), who were randomly assigned to either of two treatments with continuous progestogens for contraception were analyzed; depot-medroxyprogesterone acetate (DMPA) or continuous levonorgestrel treatment with subdermal implants (Norplant), respectively. Forearm bone density (BMDprox) increased with 2.94% (p = 0.006) in women who were prescribed levonorgestrel, which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate; group difference at 6 months for BMDprox 3.4% (95% CI 1.3, 5.5; p = 0.025) and BMDdist 4.1% (95% CI - 1.3, 9.6; p = 0.077). The changes in bone density were consistent with the changes in biochemical indices for bone metabolism; DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase (p = 0.004) and osteocalcin (p = 0.007). The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA, in standard clinical doses for contraception.

PIP: Researchers randomly allocated 22 premenopausal women aged 20-45 to treatment with either Depo-Provera (150 mg depot-medroxyprogesterone acetate [DMPA] injected intramuscularly every 3 months) or Norplant (30-60 g levonorgestrel/day during 1st year of use) to determine the differences in the short-term effects (at 6 months) on bone mass and bone metabolism. The women, clients of the Family Planning Unit of the University Hospital in Uppsala, Sweden, gave their informed consent to try either of the types of continuous progestogen contraception. The researchers examined biochemical indices for bone metabolism. Alkaline phosphatase and osteocalcin increased significantly in the levonorgestrel group (1.88-2.26 mckat/l [p = 0.004] and 1.22-3.05 mcg/l [p = 0.007], respectively). DMPA increased bone turnover (serum calcium: 2.33-2.38 [p = 0.038]; urine hydroxyproline/creatinine ratio: 12.1-24) and bone formation (serum osteocalcin: 1.2-1.61). Women treated with levonorgestrel experienced a 2.94% increase in forearm bone mineral density (BMDprox) (p = 0.006), while women treated with DMPA experienced an insignificant 0.41% decrease in BMDprox. These changes in BMDprox corresponded with the changes in the biochemical indices for bone metabolism. These findings reveal that treatment with levonorgestrel at standard clinical doses for contraception increases bone density, while treatment with DMPA at standard clinical doses for contraception does not affect bone density.