Does the Pill affect bone mineral density?

When you name the noncontraceptive benefits offered by today’s low-dose oral contraceptives (OCs), you can list protective effects against endometrial cancer, ovarian cancer, benign breast disease, ovarian cysts, ectopic pregnancy, pelvic inflammatory disease, and anemia. What if a definitive study could show that use of pills is associated with favorable effects on bone mineral density (BMD)?

Osteoporosis is a major public health threat for 28 million Americans, 80% of whom are women, according to the National Institutes of Health’s Osteoporosis and Related Bone Diseases National Resource Center in Washington, DC.1 One of every two women over 50 will have an osteoporosis-related fracture in her lifetime. (For more on osteoporosis, see Contraceptive Technology Update, June 2000, p. 71.)

Researchers at the Boston University School of Medicine have performed a retrospective review of the literature to determine the association of OC use and BMD.2 Their conclusion? Based on the review of 13 studies, fair evidence supports the hypothesis that the use of low-dose OCs is associated with favorable effects on BMD.

"The review was motivated by curiosity, since low-dose OCs have not been considered separately. Perhaps they should be," says Lynn Borgatta, MD, clinical associate professor in the obstetrics/gynecology department in Boston University’s medical school and a review co-author.

The just-published review was limited to studies of women using low-dose OCs with BMD measurement analyzed by bone densitometry. A total of 13 studies met the inclusion criteria. Nine of the studies showed a positive effect of OC use on BMD,3-11 and four did not show an association.12-15 However, none of the studies showed a decrease in BMD with OC use. The researchers classified the level of evidence from each study according to the guidelines of the U.S. Preventive Services Task Force.16

The researchers offer suggestions for a randomized, controlled study design to yield more definitive results.

Can OCs make an impact?

Will a randomized, controlled study be able to show that OC use does have a major impact on the BMD of healthy, ovulatory women? Andrew Kaunitz, MD, says he is skeptical. Kaunitz is professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville and director of menopause and gynecology services at the Medicus Women’s Diagnostic Center in Jacksonville. Based on the existing literature, he does not see OC use having a major positive effect on the BMD of healthy, ovulatory women. That should not be surprising, because such women are already estrogen replete, he notes.

"In contrast, combination OCs have consistently been found to positively impact BMD in hypoestrogenic women, including those with eating disorders [anorexia], hypothalamic amenorrhea, and perimenopausal women," Kaunitz says. "It is in these latter high-risk women where use of OCs can make an important positive impact."

A recently published study that measured BMD in long-term OC users and compared it to levels in menstruating women who had never used pills found no differences in bone density.17 This finding should not be a surprising one, says John Guillebaud, MA, FRCS(Ed), FRCOG, MFFP, professor of family planning and reproductive health at University College and medical director of the Margaret Pyke Family Planning Centre, both in London.

"You cannot expect the OC estrogen to provide an additional advantage in comparison with women with normal ovarian function, only in a population which includes a good proportion who have diminished ovarian function," he explains. "That is why the positive studies tend to be in the older age groups when the comparison population has an increasing proportion of women with hypo-estrogen levels, due to the beginnings of ovarian failure prior to their menopause."

According to Guillebaud, in studies of younger women, only about 2% to 5% would be expected to be short of estrogen. Although those women certainly would benefit from the Pill, there would be too few of them in the average study to show a population difference, he concludes.

"There is no particular need for a definitive study; in my view, our study shows the Pill is as good as a woman’s own ovaries, and the positive studies show it is better than a woman’s defective ovaries," he says. "To confirm the latter, one could randomly allocate underweight athletes with oligomenorrhea to the combined OC or to nonhormonal contraception, or target older women above age 45 [who are without contraindications] for a similar randomized controlled trial."

Guillebaud says the results of such a study would show that the estrogen of the OC works just as well as ERT and neither better nor worse than a woman’s own ovarian estrogen with respect to bone health. "What is often overlooked is that estrogen is estrogen wherever it comes from."

References

1. National Institutes of Health. "Osteoporosis and Related Bone Diseases National Resource Center." Osteoporosis Overview. Washington, DC. Web: www.osteo.org/ osteo.html.

2. Kuohung W, Borgatta L, Stubblefield P. Low-dose oral contraceptives and bone mineral density: An evidence-based analysis. Contraception 2000; 61:77-82.

3. Kanders B, Lindsay R, Dempster D, et al. Determinants of bone mass in healthy young women. Proceedings of the Copenhagen International Symposium of Osteoporosis. Copenhagen: 1984, pp. 337-339.

4. Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: A three-year prospective study. Int J Fertil 1985; 30:15, 18-28.

5. Recker RR, Davies KM, Hinders SM, et al. Bone gain in young adult women. JAMA 1992; 268:2,403-2,408.

6. Mais V, Fruzzetti F, Ajossa S, et al. Bone metabolism in young women taking a monophasic pill containing 20 mcg ethinyl estradiol: A prospective study. Contraception 1993; 48:445-452.

7. Volpe A, Silferi M, Genazzani AD, et al. Contraception in older woman. Contraception 1993; 47:229-239.

8. Gambacciani M, Spinetti A, Cappagli B, et al. Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: Effects on bone mineral density and metabolism. Maturitas 1994; 19:125-131.

9. Gambacciani M, Spinetti A, Taponeco F, et al. Longitudinal evaluation of perimenopausal vertebral bone loss: Effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism. Obstet Gynecol 1994; 83:392-396.

10. Volpe A, Amram A, Cagnacci A, et al. Biochemical aspects of hormonal contraception: Effects on bone metabolism. Eur J Contraception Repro Health Care 1997; 2:123-126.

11. Masaryk P, Lunt M, Benevolenskaya L, et al. Effects of menstrual history and use of medications on bone mineral density: The EVOS Study. Calcif Tissue Int 1998; 63:271-276.

12. Sowers M, Wallace RB, Lemke JH. Correlates of forearm bone mass among women during maximal bone mineralization. Prev Med 1985; 14:585-596.

13. Mazess RB, Barden HS. Bone density in premenopausal women: Effects of age, dietary intake, physical activity, smoking, and birth-control pills. Am J Clin Nutr 1991; 53:132-142.

14. Rodin A, Chapman M, Fogelman I. Bone density in users of combined oral contraception. Br J Fam Plann 1991; 16:125.

15. Murphy S, Khaw KT, Compston JE. Lack of relationship between hip and spine bone mineral density and oral contraceptive use. Eur J Clin Invest 1993; 23:108-111.

16. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Washington, DC: U.S. Department of Health and Human Services; 1996.

17. MacDougall J, Davies MC, Overton CE, et al. Bone density in a population of long term oral contraceptive pill users does not differ from that in menstruating women. Br J Fam Plann 1999; 25:96-100.