Does progesterone replacement therapy cause weight gain or increased hunger?

Progesterone Replacement Effects on Appetite and Weight

Yes, progesterone replacement therapy can increase appetite and lead to weight gain in some individuals, particularly when used as a progestin analog for cancer cachexia treatment.

Effects on Appetite

• Progesterone analogs (such as megestrol acetate) significantly improve appetite compared to placebo, with a relative risk of 2.57 (95% CI, 1.48 to 4.49) according to a Cochrane review 1
• Multiple randomized controlled trials have demonstrated that progestins improve appetite, nutritional intake, and mood in patients with cancer cachexia 1
• The appetite-stimulating effect is one of the primary reasons progestins are recommended for cancer patients experiencing anorexia 1
• The mechanism may involve a decrease in cytokine levels, which appears to be involved in the anti-anorectic effects of progestins 1

Effects on Weight

• Progesterone replacement therapy is associated with weight gain, with a relative risk of 1.55 (95% CI, 1.06 to 2.26) for weight gain compared to placebo 1
• The weight gain tends to be modest and primarily affects body fat mass rather than lean body mass 1
• Higher doses of progestins (such as megestrol acetate 480-800 mg/day) are associated with greater improvement in weight than lower doses 1
• In cancer patients, stabilization or improvement in body fat mass can be achieved with progestins, whereas no impact on fat-free or muscle mass has been reported 1

Considerations for Menopausal Women

• For menopausal women using hormone replacement therapy (HRT), the evidence on weight gain is different from that seen with high-dose progestin therapy for cancer cachexia 1
• A Cochrane review found no statistically significant difference in mean weight gain between those using estrogen/progestogen therapy and non-HRT users (-0.47 kg, 95% CI -1.63,0.69) 2
• Some studies suggest that combined HRT may actually help prevent an increase in body fat mass and fat redistribution that typically occurs during menopause 3
• One small study found that combined HRT with estradiol and medroxyprogesterone acetate favored weight loss by significantly increasing lipid oxidation after 3 months of treatment 4

Potential Side Effects and Risks

• Progestin therapy is associated with increased risks of edema (RR, 1.36; 95% CI, 1.07 to 1.72) 1
• There is a significant risk of thromboembolic events (RR, 1.84; 95% CI, 1.07 to 3.18) with progestin therapy 1
• In some studies, progestin therapy was associated with increased risk of death (RR, 1.42; 95% CI, 1.04 to 1.94) 1
• For women concerned specifically about weight gain with contraceptives, copper IUDs and barrier methods are more weight-neutral options than hormonal methods 5

Special Populations

• Adolescents who are overweight or obese and using depot medroxyprogesterone acetate (DMPA) may gain more weight than normal-weight DMPA users 6
• Individual responses to hormonal treatments vary considerably, and some women may be more susceptible to weight changes than others 5

In summary, progesterone replacement therapy, particularly at higher doses used for conditions like cancer cachexia, can increase appetite and lead to weight gain. However, standard hormone replacement therapy for menopausal symptoms appears to have minimal impact on weight compared to the natural weight changes that occur during menopause.