What is the effect of progesterone injections on blood sugar levels?

Effect of Progesterone Injections on Blood Sugar Levels

Vaginal progesterone has not been associated with an increased risk of gestational diabetes mellitus or glucose intolerance. 1

Mechanism and Impact

Progesterone is a steroid hormone with multiple physiological effects beyond its traditional role in female fertility and pregnancy. When considering its impact on blood glucose levels:

• The FDA label for injectable progesterone notes that "a decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination treatment," though the mechanism is described as "obscure" 2
• The FDA specifically recommends that "diabetic patients should be carefully observed while receiving such therapy" 2
• This effect appears to be more pronounced with combination hormone therapy rather than with progesterone alone

Route of Administration Considerations

The effect of progesterone on blood sugar may vary based on the route of administration:

• Intramuscular (IM) progesterone: May have higher systemic absorption and potentially greater metabolic effects
• Vaginal progesterone: Has a "first uterine pass effect" with preferential distribution to the uterus rather than systemic circulation 3, which may result in fewer systemic side effects including metabolic changes
• Oral progesterone: Undergoes significant first-pass metabolism (>90%) in the liver, resulting in high levels of progesterone metabolites that may have different effects than the parent compound 4

Clinical Evidence

The Society for Maternal-Fetal Medicine (SMFM) specifically addresses this concern in their 2024 guidelines, stating:

• "Vaginal progesterone has not been associated with an increased risk of gestational diabetes mellitus or glucose intolerance" 1
• This statement is made in the context of discussing potential risks or contraindications to treatment with vaginal progesterone

Special Populations

Pregnant Women

For pregnant women receiving progesterone for preterm birth prevention:

• No significant association between vaginal progesterone and gestational diabetes has been reported in clinical trials 1
• The SMFM recommends continuous monitoring of blood glucose in the postoperative period for patients undergoing CABG to maintain levels ≤180 mg/dL to reduce adverse events 1

Diabetic Patients

For patients with pre-existing diabetes:

• More careful monitoring of blood glucose levels is recommended when initiating progesterone therapy 2
• The FDA label specifically advises that "diabetic patients should be carefully observed while receiving such therapy" 2

Clinical Recommendations

1. For non-diabetic patients: Routine monitoring of blood glucose is not necessary when using progesterone, particularly with vaginal administration

2. For diabetic patients or those at risk for diabetes:

   • Monitor blood glucose more frequently when initiating progesterone therapy
   • Consider vaginal rather than intramuscular or oral routes when possible, as this may minimize systemic effects
   • Be vigilant for signs of worsening glucose control

3. For pregnant women receiving progesterone for preterm birth prevention:

   • Standard gestational diabetes screening is sufficient, as progesterone (particularly vaginal) has not been associated with increased risk of gestational diabetes 1

While progesterone may theoretically affect glucose metabolism, clinical evidence suggests this effect is minimal with modern formulations and routes of administration, particularly with vaginal progesterone. The most authoritative and recent guideline from SMFM (2024) specifically states that vaginal progesterone has not been associated with increased risk of glucose intolerance.