Does progesterone cause weight gain?

Progesterone and Weight Gain

Yes, progesterone can cause weight gain, primarily by increasing fat mass rather than lean body mass. This effect is well-documented in clinical guidelines, particularly with progestational agents like megestrol acetate and medroxyprogesterone acetate.

Evidence for Progesterone-Related Weight Gain

Progestins in Clinical Guidelines

The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines clearly state that progestins increase appetite and body weight 1. Specifically:

• Progestins like megestrol acetate increase appetite, nutritional intake, and body weight
• The weight gain is primarily in fat mass, not in fat-free or muscle mass
• This effect is so reliable that progestins are actually recommended to stimulate appetite in cancer patients with cachexia

Mechanism and Pattern of Weight Gain

Progesterone-related weight gain occurs through several mechanisms:

• Increased appetite stimulation 1
• Fluid retention leading to edema 1
• Increased fat deposition rather than lean mass 1

The 2021 ESPEN guidelines specifically note that "progestins (megestrol acetate and medroxyprogesterone acetate) increase appetite and body weight but not fat-free mass" 1.

Specific Progestin Formulations and Weight Gain

Depot Medroxyprogesterone Acetate (DMPA)

DMPA shows the strongest evidence for weight gain among progestin-only contraceptives:

• About 25% of DMPA users experience significant early weight gain (>5% of baseline weight within 6 months) 2
• Those who gain >5% weight in the first 6 months continue to gain weight at a much faster rate (0.35 kg/month vs 0.08 kg/month) 2
• Risk factors for excessive weight gain include:
  • BMI less than 30 (OR 4.00)
  • Prior pregnancies (OR 2.23)
  • Self-reported increased appetite (OR 3.06)

Other Progestin-Only Contraceptives

Research on progestin-only contraceptives shows variable effects:

• Norplant users showed greater weight gain than IUD users or those using no hormonal method 3
• For most progestin-only contraceptives, mean weight gain is typically less than 2 kg over 12 months 3

Important Clinical Considerations

Predicting and Monitoring Weight Gain

• Early weight gain (>5% within 6 months) strongly predicts continued excessive weight gain 2
• Adolescents may be particularly vulnerable to progesterone-induced weight gain 4
• Overweight teens have increased risk for weight gain while using DMPA 4

Patient Perception vs. Reality

Patient perception of weight gain with progestin methods is generally accurate:

• The sensitivity and specificity of perceived weight gain are 74.6% and 84.4%, respectively 5
• Women who perceived weight gain experienced a mean weight gain of 10.3 pounds 5

Clinical Applications

When considering progesterone therapy:

1. Assess baseline risk factors for excessive weight gain:

   • Age (adolescents at higher risk)
   • Current BMI (overweight individuals may be more susceptible)
   • Prior history of weight gain with hormonal methods

2. Monitor weight regularly, especially during the first 6 months of therapy

   • Early weight gain >5% of baseline is a strong predictor of continued excessive gain

3. Consider alternative options if weight gain is a significant concern for the patient

   • Non-hormonal methods may be preferable for patients highly concerned about weight gain

4. Recognize therapeutic uses of progesterone's weight gain effect

   • In cancer patients with cachexia, progestins are deliberately used to increase appetite and weight 1, 6

While low-dose progesterone may not significantly affect weight in some contexts 7, clinical evidence strongly supports that therapeutic doses of progesterone, particularly in formulations like DMPA and megestrol acetate, do cause weight gain primarily through increased fat mass.