Hormonal Contraception and Bone Mineral Density

Mags E Beksinska; Jennifer A Smit

Expert Rev of Obstet Gynecol. 2011;6(3):305-319.

Abstract and Introduction

Abstract

The long-acting progestogen injectable contraceptives depot medroxyprogesterone acetate and norethisterone enanthate have been found to adversely affect bone mineral density in adult premenopausal women and adolescents. The effect of combined oral contraceptives on bone mineral density is variable, with no effect reported in premenopausal women; however, growing evidence suggests that low-dose combined oral contraceptives may be detrimental to bone mineral density in adolescents and young women. Much less information is available on other hormonal methods. Concerns regarding bone loss in depot medroxyprogesterone acetate users resulted in a US FDA black-box warning for this method. No restriction has been placed on the use of other progestogen-only or combined oral contraceptive methods. There are now concerns that these recommendations should be reviewed as new information emerges regarding low-dose combined oral contraceptives and evidence grows that supports recovery of bone mineral density postdiscontinuation of depot medroxyprogesterone acetate. There is a need to balance loss of bone mineral density with the benefit of effective contraception, especially in adolescents.

Introduction

Bone mass increases rapidly from birth, and during adolescence women will gain 40–50% of their skeletal mass.^[1] Up to 90% of total adult bone content will be accumulated by the age of 20 years.^[2] Bone mineral density (BMD) remains fairly stable in adult premenopausal women,^[3] followed by bone loss over and above age-related loss in association with the menopause.^[4] It is important to know what factors affect peak bone mass in young women and bone loss in older women, as these are the chief determinants of a woman's susceptibility to osteoporosis.

Bone mineral density is one way of measuring bone strength. A BMD test measures how many grams of calcium and other bone minerals are packed into a segment of bone.^[5] The WHO has developed a classification system that uses the population mean as a reference against which a BMD measurement can be compared.^[6] A BMD measurement can be reported as a T-score and is expressed in standard deviations (SDs) from the normal population mean. In many studies a Z-score is reported, which is the difference in SDs between the BMD in users of a hormonal contraceptive method and nonuser controls in the same age group. The definition of normal BMD is no more than 1 SD below the young adult normal value. Low bone mass (osteopenia) is defined as 1–2.5 SDs below the population mean, and below this level osteoporosis is diagnosed.^[6]

Hormonal status, including reproductive hormones, are known to affect peak bone mass and bone maintenance.^[7] The relationship between estrogen deficiency and bone loss clearly suggests that hormonal contraceptive use may affect BMD. The noncontraceptive benefits of higher dose estrogen and progestin combined oral contraceptives (COCs) have included treatment of hypoestrogenic conditions in women where BMD is affected.^[8] Conversely, concerns have been raised regarding progestogen-only contraceptives, as the absence of estrogens from these methods and the resulting hypoestrogenic effect could lead to suppression of bone mass acquisition. In particular, concern is greatest in the age groups where BMD is in transition; younger women who have yet to reach peak bone mass and older women entering perimenopause and menopause where age-related bone loss has commenced.

1 2 3 4 5 6 7 8 9 10 11

Next Section

Cite this: Hormonal Contraception and Bone Mineral Density - Medscape - May 01, 2011.

Table 1. Summary of evidence for bone mineral density outcome in users of combined hormonal contraception.
Method	Outcome	Ref.
	BMD outcome
Combined oral	Adolescents:
	Longitudinal studies have found that, although BMD does not decrease in COC users, the comparison control groups, in some studies, show increases in BMD. Some of these studies have, in addition to controls, included DMPA users; COC users generally have higher BMDs in comparison to these. The current literature appears to point towards low-dose COC preparations compromising active bone growth, in that BMD values appear to remain static	[22,29–44]
	Adult premenopausal:
	Both prospective and cross-sectional studies of COC use and BMD outcome in adult users have shown few differences between current users and nonusers. Emerging evidence points to a small loss of BMD in some studies of very low-dose COCs	[21–28]
	Perimenopausal:
	A small number of prospective studies have shown that COC-treated perimenopausal women will maintain or increase their BMD. Most cross-sectional studies do not show any significant difference between COC users and nonusers	[14,22,45–52]
	Postmenopausal:
	In a limited number of prospective studies, including one where women were treated with COCs, researchers found that spinal BMD increased. Evidence from cross-sectional studies suggests that past COC use does not confer any benefits postmenopause.	[22–53]
	In summary, COC use and BMD outcome appears to vary by age group, with few differences found in current adult users in both prospective and cross-sectional studies compared with control nonusers. However, very low-dose COCs may cause small decreases in BMD. In perimenopausal and menopausal women evidence suggests that there may be benefits to using COCs, with users gaining or maintaining their BMD. There is growing concern, as the body of evidence related to adolescent users of COCs use increases, that low-dose COC formulations may be detrimental to BMD in an age group who are yet to reach peak bone mass and should show increases in BMD over time
Combined vaginal ring	Adult premenopausal:
	There is limited evidence from two studies. One 2-year cohort found baseline BMD maintained in ring users, but increased in nonuser controls. One RCT finding observed no difference in BMD between patch, vaginal ring and nonusers	[22,56,57]
Combined injectables	Adult premenopausal:
	Limited evidence exists from two studies for this method. One RCT showed no difference in BMD between Mesigyna (Bayer Schering Pharma, Leverkusen, Germany) and IUD users over 2 years, and one cross-sectional study comparing Mesigyna and Cyclofem® (The Concept Foundation, Geneva, Switzerland) with IUD users found no differences in BMD	[22,54,55]
Combined patch	Adult premenopausal:
	There is limited evidence from one RCT finding no difference in BMD between the patch, vaginal ring and nonusers	[56]
	Fracture outcome
Combined oral	Studies reporting on fracture outcome have produced conflicting results with few good-quality studies. A limited number of cohorts have found increased risks among users while some studies have found no effect or a protective effect. No information available for other methods	[10–20]

BMD: Bone mineral density; COC: Combined oral contraceptive; DMPA: Depot medroxyprogesterone acetate; IUD: Intrauterine device; RCT: Randomized controlled trial.

Table 2. Summary of evidence for bone mineral density outcome in users of progestogen-only hormonal contraception.
Method	Outcome	Ref.
	BMD outcome
DMPA-IM	Adolescents:
	Both longitudinal and cross-sectional studies show evidence of decreases in BMD in adolescent and young women current users of DMPA. Availability of a few longer follow-up studies and many of the prospective studies affected by poor follow-up due to young women discontinuing use of their contraceptive methods	[27,28,33–38, 43,44,76,77, 92–98,114]
	Adult premenopausal:
	Most longitudinal studies have shown that current adult users of DMPA may lose approximately 5–7% of bone; however, the rate of loss decreases over time. This loss appears to commence from approximately 6 months of use and appears linear for the first 2 years. Studies that have followed up users for longer than 2 years have found that the initial loss plateaus and by 5 years the loss may stabilize, although recovery does not occur during use. On discontinuation of DMPA, BMD increases regardless of age, and within a 2–3-year period BMD recovered to the level of a comparable non-DMPA user population. In summary, the cross-sectional studies have generally shown lower BMD values compared with nonuser controls in central sites such as the spine but not consistently with the hip. In most studies where forearm BMD has been measured, there appears to be minimal or no change in BMD. Decrease in BMD appears to be linked to duration of use, with those using DMPA for longer being more compromised	[24,25,28,36, 64,67–91,114]
	Perimenopausal:
	There are limited data available on DMPA use in this group of older women owing to the low prevalence of use in this age group. Information in this age group has come from studies that included a wider age range of women. However, loss of BMD has been found in these older DMPA users	[75,89,99,100,114]
	Post discontinuation:
	Evidence from adult and adolescent studies has shown that BMD recovers postdiscontinuation. Duration of exposure may affect speed of recovery. Studies suggest that recovery takes between 1 and 5 years depending on the site measured	[44,67,73,83, 84,91,94,97,101–104]
DMPA-SC	Adult premenopausal:
	There is limited evidence available from one longitudinal study comparing DMPA-IM with DMPA-SC. Both groups lost a similar percentage of BMD over 2 years. Recovery was found in a small subgroup of discontinuers of both methods postdiscontinuation	[65]
NET-EN	Adolescents:
	One longitudinal study in adolescents found lower BMD values after 5 years; some recovery was seen in a small number of discontinuers	[43,44,92]
	Adult premenopausal:
	One large cross-sectional study found lower values in current users. No difference was found between ex-users and never-users in this study	[67]
	Perimenopausal:
	One cross-sectional study found no difference between long-term current users and nonuser controls	[99]
Contraceptive implants	Adult premenopausal:
	A limited number of studies have shown no effect of implants on BMD. Several have measured the forearm only, including the largest cross-sectional study that found that current users had slightly lower BMD values in the ulna. No information was provided on recovery following discontinuation	[38,73,80,86,105–111]
Progesterone-only oral contraceptives	Adult premenopausal:
	There is very limited evidence from one small study, therefore it is not possible to draw conclusions on the relationship between this method and BMD	[112]
Progesterone vaginal ring	Adult premenopausal:
	Very limited information from one cross-sectional study on breastfeeding ring users compared with IUD users. No difference was found between these two groups in BMD at central sites	[110]
Levonorgestrel-releasing intrauterine systems	Adult premenopausal:
	There is very limited information in one cross-sectional study comparing the levonorgestrel intrauterine system with IUD users, which found no difference in forearm BMD compared with IUD users	[113]
	Fracture outcome
DMPA-IM	Limited data show a slight increase of fracture with DMPA-IM	[17,65,66]

BMD: Bone mineral density; COC: Combined oral contraceptive; DMPA: Depot medroxyprogesterone acetate; DMPA-SC: DMPA-subcutaneous; IUD: Intrauterine device; NET-EN: Norethisterone enanthate.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.