Applied Evidence

DMPA’s effect on bone mineral density: A particular concern for adolescents

Author and Disclosure Information

 

References

These studies established that bone density decreases with the initiation of DMPA, but none of them addressed the key issue of whether BMD remains at lower levels long term (ie, decades) and thereby increases future fracture risk.

Studies of adolescents. Fewer studies have examined the relationship between DMPA use and BMD in adolescents ( TABLE 2 ). Most available studies have small sample sizes and methodological limitations (high dropout rates, different age criteria, and significant differences in the comparison groups). In this population, DMPA seems to cause a mild decrease in BMD. There are not enough data to evaluate BMD recovery after DMPA discontinuation. Therefore, it is hard to extrapolate the information about BMD in an adolescent to future fracture risk.

One study examined serum estradiol levels and BMD in 22 adolescents ages 15 to 19 years who were new users of DMPA.16 Only 6 participants were still using DMPA at 1 year, and 4 used it throughout the 2 years of the study. The trend over 2 years was toward decreasing BMD. Serum estradiol levels were low, but were not correlated with BMD.

Another related study measured bone biochemical markers in 3 groups: 53 adolescents ages 12 to 18 starting DMPA; 165 adolescents starting oral contraceptive pills; and 152 adolescent women not using hormonal contraception.17 There was no relationship between bone biochemical markers and BMD at either the LS spine or the femoral neck.

TABLE 1
DMPA’s effect on BMD in adult women: What the studies reveal

AUTHOR (TYPE OF STUDY)# OF PARTICIPANTS/ POPULATION DESCRIPTIONOUTCOME MEASURERESULTSCOMMENTS
Gbolade, 199824 (cross-sectional) N=185
Ages 17-52 (mean 33)
Using DMPA for 1-16 years
DEXA of LS spine and femoral neckZ-score lower at LS spine (P<.001) but not at the femoral neck (P=.25)No significant association between duration of DMPA use and Z-score
Ryan, 200225 (cross-sectional) N=32
Ages 19-53
Using DMPA >2 years
Low serum estradiol level or menopausal symptoms
DEXA of LS spine and femoral neckZ-scores were lower at both femoral neck (-0.84; 95% confidence interval [CI], -1.17 to -0.52) and LS spine (-0.32; 95% CI, -0.62 to -0.02)18 women had osteopenia at LS spine
3 women had osteoporosis at LS spine
Petitti, 200026 (cross-sectional) n=350 (DMPA)
n=695 (control)
Ages 30-34
Using DMPA ≥2 years
Control group: women who never used hormonal contraception
SXA of wristBMD was lower for DMPA current users vs nonusers 0.465 vs 0.471 g/cm2 in midshaft ulna (P<.001) 0.369 vs 0.382 g/cm2 in distal radius (P<.001)Large WHO-sponsored, multinational study
Past users of DMPA had bone densities not significantly different from nonusers
Large variations in BMD among sites
Wanichsetakul, 200227 (cross-sectional) n=34 (DMPA)
n=62 (comparison)
Ages 30-34
Using DMPA ≥2 years
Comparison groups of women on no steroid contraception in prior 6 months
DEXA of LS spine, distal radius, and femoral neckBMD at femoral neck and distal radius was not different between DMPA users and controls (P=.335 and P=.398)
DMPA users had lower BMD at LS spine (P=.007)
Study conducted in Thailand
Beksinska, 200528 (cross-sectional) n=127 (DMPA)
n=161 (comparison)
Ages 40-49
Using DMPA ≥1 year
DEXA of radius and ulnaNo significant difference in BMD at distal radius (P=.26) or ulna (P=.21)Higher BMD was associated with higher BMI
Higher FSH levels were associated with lower BMD
Tang, 200029 (cohort) N=59
Ages 37-49
Using DMPA for a mean of 10 years
DEXA of LS spine and femoral neck
Annual measurements for 3 years
Small annual decreases in BMD at LS spine (-0.44%), femoral neck (-0.4%), and Ward’s triangle (-1.05%)Duration of DMPA use not related to BMD
Decreases in BMD less than projected for age
Study conducted in China
Scholes, 200213 (cohort) n=183 (DMPA)
n=258 (comparison)
Ages 18-39
Comparison group not exposed to DMPA
DEXA of LS spine and proximal femur
Measurements every 6 months for 4 years
Total hip and LS spine BMD were lower for DMPA users (P=.002 at LS spine; P<.005 for proximal femur)New users lost bone faster than longer-term users
Women who discontinued DMPA showed increasing BMD levels, which reached levels of nonusers after 30 months
33% dropout rate among both groups at 3 years, 44% of DMPA users discontinued use within first 6 months of the study
Cundy, 199411 (cohort) n=36 (DMPA)
n=18 (comparison)
Ages 25-51 (mean 41-45)
14 women had used DMPA for ≥3 years and discontinued
22 women were long-term DMPA users
Individuals in comparison group were never users of DMPA
DEXA of LS spine and femoral neck
Measured twice in each woman
Group I (discontinuers) BMD change at LS spine 3.4% per year (1.6% to 5.2%) and at femoral neck 0.8% per year (-1.8% to 3.4%)
Group II (long-term users) BMD change at LS spine -0.2% per year (-2.0% to 1.6%) and at femoral neck -1.1% per year (-2.6% to 0.4%)
Group III (nonusers) BMD change at LS spine 0.3% per year (-2.2% to 2.8%) and at femoral neck -1.5% per year (-3.2% to 0.2%)
BMD in LS spine in both groups of DMPA users was 9% lower than control group at baseline
Berenson, 200130 (cohort) n=33 (DMPA)
n=59 (comparison)
Ages 18-33
New users of DMPA
Comparison group not using any hormonal contraception
DEXA at LS spine
2 measurements for each participant 12 months apart
Adjusted percent change in BMD for DMPA users was -2.7% (-4.44% to -1.05%) and in nonusers was -0.37% (-1.98% to 1.25%), P=.0139% dropout rate among both groups
Merki-Feld, 200031 (cohort) N=36
Ages 30-45
Using DMPA ≥6 months
Quantitative CT of radius
Measured twice over 12 months
Trabecular bone mass increased 1.6% (P=.8)
Cortical bone mass decreased 0.6% (P<.04)
Duration of DMPA use was not associated with BMD change
Clark, 200414 (cohort) n=178 (DMPA)
n=145 (comparison)
Ages 18-35
New users of DMPA
Comparison group not using hormonal contraception
DEXA of LS spine and total hip
Measured every 3 months for 2 years
At 24 months, change in BMD in DMPA users was -5.8% (SE=0.096) at hip and -5.7% (SE=0.034) at LS spine
Significant difference between DMPA group and comparison group (P=.001)
Dropout rate 22% in both groups over 2 years
Duration of use predicted decrease in BMD
Among DMPA users, increasing BMI was protective against BMD loss at hip
Kaunitz, 200615 (cohort) n=248 (DMPA)
n=360 (comparison)
Ages 25-35
New users of DMPA
Comparison group not using hormonal contraception
DEXA LS spine, total hip, femoral neck, and trochanter
Measured at baseline and every 48 weeks for up to 5 years
Mean decrease in BMD in DMPA users was 5.16% (±3.6) at hip and 5.38% (±3.57) at LS spine
At 96 weeks after discontinuation, change was -0.20% at hip and -1.19% at LS spine
Decreases in BMD were linearly associated with duration of use up to 5 years
17% of DMPA group and 33% of comparison group completed entire 5 years of study
Clark, 200612 (cohort) n=178 (DMPA)
n=145 (comparison)
Ages 18-35
New DMPA users
Comparison group not using hormonal contraception
DEXA total hip and LS spine
Measured every 3 months for up to 4 years
Mean change in BMD in DMPA users was -7.7% (±0.11) at hip and -6.4% (±0.36) at LS spine
DMPA users of 24-36 months had BMD of -4.7% (hip) and -2.9% (spine) compared with baseline 18 months after discontinuation
Most loss was noted first 2 years after initiation of DMPA
Most users of DMPA up to 2 years returned to baseline BMD by 3 years
36% dropout rate in both groups after second year of study
Only 45% of DMPA group completed 4 years of study
BMD, bone mineral density; BMI, body mass index; CT, computed tomography; DEXA, dual-energy x-ray absorptiometry; DMPA, depot- medroxyprogesterone acetate; FSH, follicle-stimulating hormone; LS, lumbosacral; SE, standard error; SXA, single-energy x-ray absorptiometry; WHO, World Health organization.

Pages

Recommended Reading

CA 125 &plus; Ultrasound Find Early Ovarian Cancer
MDedge Family Medicine
Birth Events Unexpectedly Common in Cerebral Palsy
MDedge Family Medicine
Bone Health Advice in Cancer Updated
MDedge Family Medicine
IVF Appears to Increase Risk of Ovarian Cancer
MDedge Family Medicine
Prior Breast Ca Warrants MRI Screen
MDedge Family Medicine
B12 Level May Predict Neural Tube Defect Risk
MDedge Family Medicine
Algorithm Predicts Epithelial Ovarian Cancer Risk
MDedge Family Medicine
Can counseling prevent or treat postpartum depression?
MDedge Family Medicine
Why women risk unintended pregnancy
MDedge Family Medicine
When to suggest this OC alternative
MDedge Family Medicine