Can Medroxyprogesterone Acetate Cause Hyperglycemia?
Yes, medroxyprogesterone acetate (MPA) can cause hyperglycemia and impair glucose metabolism, particularly in women at high risk for diabetes, those with existing insulin resistance, and patients with lipodystrophy.
Evidence from Guidelines and Drug Labeling
The FDA drug label for medroxyprogesterone acetate explicitly warns that "a decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination treatment" and specifically states that "diabetic patients should be carefully observed while receiving such therapy" 1. This represents the highest level of regulatory guidance on this issue.
Multiple clinical practice guidelines corroborate this concern:
The 2007 Diabetes Care guidelines on gestational diabetes specifically note that in Latino breastfeeding women, depot medroxyprogesterone acetate (DMPA) was associated with a two- to threefold increase in diabetes risk, leading to the recommendation that "progestin-only agents should be used with caution during breastfeeding" 2.
The 2021 Blood Reviews guidelines on hormone replacement therapy acknowledge that MPA may negatively impact carbohydrate metabolism more than alternative treatment options 2.
The 2012 U.S. Preventive Services Task Force systematic review found that diabetes incidence was reduced in women receiving estrogen plus progestin (HR 0.79), but this protective effect was not seen with estrogen-only therapy, suggesting the metabolic effects vary by formulation 2.
Mechanism and Clinical Impact
MPA causes a persistent increase in insulin levels during glucose loading, indicating insulin resistance 3. The metabolic effects include:
Elevated fasting glucose levels: DMPA users experience increases of 2-3 mg/dL over the first 30 months of use 4.
Elevated insulin levels: Increases of 3-4 units occur within the first 18 months, then plateau 4.
Impaired glucose tolerance: Both fasting and post-load glucose values are affected, with the mean area under the glucose curve significantly elevated as early as 1 month after initiation 5.
High-Risk Populations Requiring Special Caution
Obese and overweight women using DMPA show more pronounced elevations in insulin and glucose levels compared to normal-weight users 4. This is particularly concerning given that:
Navajo women using DMPA had 3.8 times higher odds of developing diabetes compared to those using combination oral contraceptives (95% CI 1.8-7.9), with risk persisting after adjustment for BMI 6.
Longer duration of use is associated with greater diabetes risk 6.
Women with lipodystrophy can experience severe hyperglycemia requiring extremely high insulin doses (up to 1,700 units/day) after a single DMPA injection 7.
Clinical Management Algorithm
For women considering MPA:
Screen for diabetes risk factors before initiation, including family history, obesity (BMI ≥25), history of gestational diabetes, and metabolic syndrome 2.
Obtain baseline fasting glucose and consider HbA1c in high-risk patients 1.
Monitor glucose levels at 6-month intervals for the first 18-30 months, as this is when metabolic changes are most pronounced 4.
Weight gain exceeding 5% at 6 months predicts excessive future weight gain and should prompt consideration of alternative contraception 8.
For diabetic patients, intensify glucose monitoring and anticipate need for medication adjustments 1, 7.
Common Pitfalls to Avoid
Failing to counsel patients about metabolic effects before initiation, which can lead to poor adherence when hyperglycemia develops 8.
Not monitoring glucose in high-risk populations, particularly women with prior gestational diabetes, obesity, or strong family history 2, 4.
Overlooking the cumulative effect of duration of use on diabetes risk 6.
Assuming all progestin-only methods have equivalent metabolic effects—levonorgestrel IUDs and progestin-only pills do not appear to increase glucose or insulin levels to the same degree as injectable DMPA 4, 5.
Alternative Contraceptive Options
For women at high risk for diabetes or with existing glucose intolerance, consider:
- Copper IUD (non-hormonal, no metabolic effects) 2
- Levonorgestrel IUD (minimal systemic absorption, no demonstrated glucose effects) 2
- Very-low-dose combined oral contraceptives (containing desogestrel 0.15 mg) do not significantly affect glucose or insulin levels 4
The evidence consistently demonstrates that MPA, particularly in injectable depot form, adversely affects glucose metabolism through increased insulin resistance, with clinically significant risk of hyperglycemia and diabetes development in susceptible populations 2, 1, 7, 4, 6.