Bone-sparing properties of oral contraceptives

doi:10.1016/S0002-9378(96)70366-6

American Journal of Obstetrics and Gynecology

Volume 174, Issue 1, Part 1, January 1996, Pages 15-20

https://doi.org/10.1016/S0002-9378(96)70366-6 Get rights and content

Abstract

Postmenopausal osteoporosis is a major health care problem that affects 20 million women in the United States and accounts for >1 million fractures per year. Hormone replacement therapy is effective for reducing bone loss in the postmenopausal women. However, intervention before menopause may delay or prevent the decline in bone mass that begins between ages 30 and 40 years. The effects of oral contraceptives on bone mass have been investigated, and a positive association between oral contraceptive use and bone mass that is directly related to the duration of oral contraceptive use was observed. The effects of oral contraceptives on bone mass may be related to the specific formation. The effect of estrogens is dose related, and the optimal dose appears to be 25 to 35 μg of ethinyl estradiol or its equivalent. Results from several studies show that norethindrone has a positive effect on bone mass. An oral contraceptive may offer optimal birth control for the older premenopausal woman who currently uses other forms of birth control. (AM J OBSTET GYNECOL 1996;174:15-20.)

Section snippets

EPIDEMIOLOGIC FACTORS IN POSTMENOPAUSAL OSTEOPOROSIS

Total body bone mass increases in women through the second decade of life, peaks during the third decade, and then stabilizes or begins to decrease up to the time of menopause.⁸ By the fifth decade approximately 10% of vertebral bone mass is lost.⁸ After menopause bone loss accelerates rapidly, ultimately leading to osteoporosis and an increased risk of hip fracture in the sixth through eighth decades. Bone loss occurs from the proximal femur, distal radius, metacarpals, and vertebral column.

EFFICACY OF ORAL CONTRACEPTIVES FOR PRESERVATION OF BONE MASS IN THE PREMENOPAUSAL OR PERIMENOPAUSAL WOMAN

In the postmenopausal woman hormone replacement therapy is effective for maintaining bone mass; however, strategies to maintain, stabilize, or preserve bone mass in the premenopause or perimenopause may be equally important. Although it has not been conclusively demonstrated that oral contraceptives preserve bone mass, a number of studies have been conducted to investigate their effects (Table I).3, 4, 5, 6, 7, 10, 11, 12 Although most studies have found that premenopausal use of oral

DOSE-RELATED EFFECTS OF ESTROGEN ON BONE

To obtain optimal benefits from the bone-sparing effects of estrogen, the appropriate contraceptive formulation must be selected. Because of the thrombotic risks of excessive estrogen doses, the United States Food and Drug Administration has recommended that the dose of the estrogenic component of oral contraceptives be as low as possible. The advent of very-low-dose oral contraceptives (≤20 μg/day) has helped reduce these thrombotic complications; however, at these very low doses the

IMPACT OF PROGESTIN COMPONENT OF ORAL CONTRACEPTIVES ON BONE MASS

The progestogenic component of oral contraceptives may also have an impact on bone mineral density, although evidence supporting the benefit of progestins is less conclusive than that of estrogens. The exact mechanism for the effect of progestins on bone metabolism is unknown. Norethindrone has demonstrated estrogen-like properties in animal models and has been shown to interact at the estrogen receptor in rats.²⁰ In perimenopausal women a portion of norethindrone was shown to be converted in

COMMENT

In healthy women >35 years old there is a need for effective, reliable birth control. Oral contraceptives may be exceptionally effective in this patient because of the lower fertility rates, less sexual frequency, and improved compliance. In addition, oral contraceptives offer noncontraceptive benefits in the older woman, such as a reduced risk of endometrial and ovarian cancer and improved control of intermenstrual bleeding.² However, the most important noncontraceptive benefit of oral

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Cited by (86)

Low BMD is an independent predictor of fracture and early menopause of mortality in post-menopausal women-A 34-year prospective study
2013, Maturitas
Identify risk factors for fragility fractures and mortality in women aged 48.
Prospective population-based observational study on 390 white north European women aged 48 at study start. At study start, we measured bone mineral density (BMD) by single-photon absorptiometry (SPA) in the distal forearm, anthropometry by standard equipment and registered menopausal status, health and lifestyle factors. Menopause before age 47 was defined as early menopause. Incident fragility fractures and mortality were recorded until the women reached age 82. Potential risk factors for fragility fracture and mortality were evaluated with Cox's proportional hazard regression analysis. Data are presented as risk ratios (RR) with 95% confidence intervals in brackets.
Incidence of fragility fractures and mortality.
In the univariate analysis, low BMD and early menopause predicted fractures. In the multivariate analysis, only BMD remained as an independent risk factor with a RR of 1.36 (1.15, 1.62) per standard deviation (SD) decrease in baseline BMD. In the univariate analysis, early menopause and smoking predicted mortality, and remained as independent risk factors in the multivariate analysis with RR 1.62 (1.09, 2.39) for early menopause and 2.16 (1.53, 3,06) for smoking.
Low BMD at age 48 is an independent predictor for fragility fractures. The predictive ability of early menopause is at least partially attributed to other associated risk factors. Early menopause and smoking were found in this study to be independent predictors for mortality.
Estrogen-progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study
2008, Contraception
Citation Excerpt :
The groups of this study did not have significant menstrual irregularities; thus, the female athlete triad does not explain the BMC differences despite the differences in baseline physical activity amounts and energy expenditure. Estrogen dose of 25–35 mcg in the premenopausal OC use seemed to be optimal in preventing or delaying the postmenopausal bone loss [43]. In this present study, all participants used formulations containing 35 mcg or less estrogen, 81% (57/70) even less than 30 mcg.
Estrogen–progestin contraception may affect estrogen production and alter the development of peak bone mass.
A 4-year follow-up with 122 adolescent women aged 12-19 years. The data were divided into three groups based on estrogen–progestin contraceptive (EPC) use: (i) nonusers (n=52), (ii) 1–2 years of use (n=24) and (iii) use for more than 2 years (n=46). The estrogen dose of the preparations was ≤35 mcg. Height, weight, and the amount of exercise (ratio of work metabolic rate, h/week) as well as bone mineral content (BMC) of lumbar spine and femoral neck were measured repeatedly.
There was a significant trend showing less of an increase in the mean adjusted BMC of lumbar spine in the group of adolescent women who had used EPC for more than 2 years compared with the two other groups. In the mean adjusted BMC of the femoral neck, there was a significant trend of a smaller increase in EPC users for more than 2 years compared with 1–2 years of use.
Long-term EPC with low-dose estrogen preparations seems to suppress normal bone mineral accrual in adolescent women.
Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study
2008, Contraception
Citation Excerpt :
Given the well-known bone protective actions of estrogens [14], the dose of these hormones in OCs can be considered one of the main factors influencing the results. Indeed, results of several clinical studies have demonstrated that the bone-sparing properties of estrogen show an extremely sensitive dose-response effect [15]. In the last few years, most clinical and experimental studies have focused on the effect exerted by the estrogen component of COCs on the skeleton and on identifying the minimal estrogen dose necessary for maintaining such beneficial actions on the bone [6,16,17].
The effects of a 21-day combined oral contraceptive containing 30 mcg ethinyl estradiol plus 3 mg drospirenone with a 21-day preparation containing 20 mcg ethinyl estradiol plus 3 mg drospirenone on bone turnover and bone mineral density (BMD) in young fertile women were compared.
A randomized, controlled trial was conducted on healthy fertile women treated with 30 mcg ethinyl estradiol plus 3 mg drospirenone (Group A; n=21), 20 mcg ethinyl estradiol plus 3 mg drospirenone (Group B; n=23) and healthy controls (Group C; n=21). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin (BGP), urinary pyridinoline and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry.
In Groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Groups A and B in urinary levels of pyridinoline and deoxypyridinoline, in calcium levels and in BGP levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values.
Both combined oral contraceptives exert a similar positive influence on bone turnover in young postadolescent women.
Combined hormonal contraception and bone health: a systematic review
2006, Contraception
This systematic review examined whether women who use combined hormonal contraception experience changes in risk of fracture or bone mineral density (BMD) that differ from nonusers. We identified 86 articles from PubMed and EMBASE (published 1966 to August 2005) that reported on fracture or BMD outcomes by use of combined hormonal contraceptives. The evidence relating to combined oral contraceptives (COCs) and fracture is inconclusive, as results from the available studies conflict. Studies of adolescent and young adult women generally found lower BMD among COC users than nonusers. Evidence for premenopausal adult women suggested no differences in BMD between COC users and nonusers. COC use in perimenopausal and postmenopausal women preserved bone mass, while nonusers lost BMD, but BMD among former COC users in this age group was the same as for never-users. Evidence for other combined hormonal methods was very limited, with one study indicating no effect of combined hormonal injectable use among premenopausal women on BMD and one study suggesting lower BMD among premenopausal users of the NuvaRing than in nonusers.
Prior oral contraception and postmenopausal fracture: A Women's Health Initiative observational cohort study
2005, Fertility and Sterility
To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.
A prospective cohort of 93,725 postmenopausal women.
Forty Women’s Health Initiative (WHI) clinical centers across the United States.
Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old.
None.
The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire.
The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01–1.15). Among women without any postmenopausal hormone treatment, past OC use for ≤5 years led to an HR of 1.15 (95% CI, 1.04–1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97–1.23) compared with never users.
This study does not support the idea that past OC use protects against later fracture.
Health benefits of combined oral contraceptives–a narrative review
2024, European Journal of Contraception and Reproductive Health Care

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^☆: From the Department of Obstetrics and Gynecology, Tufts University School of Medicine, New England Medical Center.

^☆☆: Reprint requests: Alan DeCherney, MD, Department of Obstetrics and Gynecology, Tufts University School of Medicine, New England Medical Center, 750 Washington St., Boston, MA 02111.

^★: 0002-9378/96 $5.00 + 0 6/1/65579

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Bone-sparing properties of oral contraceptives☆,☆☆,★

Abstract

Section snippets

EPIDEMIOLOGIC FACTORS IN POSTMENOPAUSAL OSTEOPOROSIS

EFFICACY OF ORAL CONTRACEPTIVES FOR PRESERVATION OF BONE MASS IN THE PREMENOPAUSAL OR PERIMENOPAUSAL WOMAN

DOSE-RELATED EFFECTS OF ESTROGEN ON BONE

IMPACT OF PROGESTIN COMPONENT OF ORAL CONTRACEPTIVES ON BONE MASS

COMMENT

Contraception

Maturitas

Bone

AM J OBSTET GYNECOL

Am J Clin Nutr

Contraception

J Steroid Biochem Med Biol

Fertil Steril

Maturitas

Lancet

HRT and osteoporosis

Reproductive health in the perimenopause

Contracept Rep