Medroxyprogesterone side effects
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Side Effects of Medroxyprogesterone: A Comprehensive Review
Introduction to Medroxyprogesterone Side Effects
Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly used in various medical treatments, including contraception and hormone replacement therapy. While effective, MPA is associated with several side effects that can impact patient compliance and overall health outcomes. This article synthesizes findings from multiple studies to provide a clear understanding of the side effects associated with MPA.
Weight Gain and Appetite Changes
One of the most frequently reported side effects of MPA is weight gain. Studies have shown that MPA can lead to significant increases in body weight and fat mass1 2. In a placebo-controlled study involving patients with advanced-stage non-hormone-sensitive cancer, MPA was found to improve appetite and prevent further weight loss, although it did not significantly enhance overall quality of life2.
Menstrual Irregularities
MPA is also known to cause unpredictable bleeding patterns, including irregular bleeding and amenorrhea (absence of menstruation)1 7 9. These menstrual irregularities are a common reason for discontinuation of MPA as a contraceptive method. In a large clinical trial comparing different dosages of depot-medroxyprogesterone acetate (DMPA), amenorrhea was a significant factor leading to discontinuation9.
Mood and Psychological Effects
The impact of MPA on mood and psychological well-being is mixed. Some studies suggest that MPA may cause mood changes, including negative mood symptoms, particularly in women with a history of premenstrual syndrome (PMS)6. However, other studies have found no consistent adverse psychological effects when MPA is used in conjunction with estrogen therapy3 8 10. In a comparison between MPA and norethindrone acetate, MPA was associated with fewer negative mood symptoms in women without a history of PMS6.
Cardiovascular Side Effects
Cardiovascular toxicity is another concern with MPA use, especially in older patients or those with pre-existing cardiovascular conditions. Fluid retention, hypertension, and thromboembolic events have been reported, although the risk is generally lower compared to other hormonal treatments like diethylstilbestrol5. The risk of severe cardiovascular complications is highest during the first six months of treatment5.
Bone Health and Hypoestrogenic Effects
MPA can mitigate some hypoestrogenic side effects when used in combination with gonadotropin-releasing hormone agonists (GnRH-A) for conditions like endometriosis. This combination has been shown to reduce hot flushes, sweating, and urinary calcium excretion, potentially offering a bone-sparing effect4.
Other Physical Symptoms
Physical side effects such as peripheral edema, breast tenderness, and vaginal bleeding have also been reported with MPA use2 8. In a study comparing MPA with micronized progesterone, MPA users reported more instances of vaginal bleeding and breast tenderness8.
Conclusion
Medroxyprogesterone acetate is associated with a range of side effects, including weight gain, menstrual irregularities, mood changes, cardiovascular issues, and other physical symptoms. While it offers benefits in specific medical contexts, patient-centered counseling should incorporate these potential side effects to ensure informed decision-making and improve treatment adherence. Further high-quality research is needed to clarify the full spectrum of MPA's side effects and benefits.
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Most relevant research papers on this topic
Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate: A Systematic Review.
DMPA use may cause weight gain, increased body fat mass, irregular bleeding, and amenorrhea, with limited evidence supporting decreased cancer risk and tubal infertility.
Systematic Review
Rigorous JournalEffects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study.
Medroxyprogesterone acetate improves appetite and may prevent further weight loss in advanced-stage non-hormone-sensitive cancer patients, but does not significantly impact overall quality of life.
RCT
Highly CitedA Randomized, Double-Blind, Placebo- Controlled, Cross-Over Trial to Assess the Side Effects of Medroxyprogesterone Acetate in Hormone Replacement Therapy
Medroxyprogesterone acetate 10 mg/day for 14 days combined with transdermal estrogen therapy does not cause consistent adverse physical or psychological effects on women for one cycle of treatment.
RCTMedroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone agonist without changing its efficacy in endometriosis.
High-dose medroxyprogesterone acetate combined with a GnRH agonist reduces hypoestrogenic side effects and may have a bone-sparing effect in endometriosis treatment without changing its efficacy.
RCTCardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762.
Diethylstilbestrol has higher cardiovascular toxicity than estramustine phosphate or medroxyprogesterone acetate, and cyproterone acetate, with the risk of severe complications increasing during the first 6 months of treatment.
RCT
Large Human TrialHighly CitedNegative mood changes during hormone replacement therapy: a comparison between two progestogens.
Medroxyprogesterone to estrogen is preferable for mood symptoms during hormone replacement therapy in women without a history of premenstrual syndrome.
RCTHighly CitedEffects of depo-medroxyprogesterone acetate as a contraceptive agent.
Depot medroxyprogesterone acetate is a highly effective contraceptive agent with unpredictable bleeding patterns and no deleterious effect on pregnancy outcome.
Observational StudyComparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women
Progesterone and medroxyprogesterone do not affect mood in early postmenopausal women, and micronized progesterone may have lesser side effects than MPA.
RCTA multicentred phase III comparative clinical trial of depot-medroxyprogesterone acetate given three-monthly at doses of 100mg or 150mg: 1. Contraceptive efficacy and side effects
Depot-medroxyprogesterone acetate (DMPA) at 100mg or 150mg doses shows little difference in efficacy and side effects, with no pregnancy occurring in the 150mg dose.
RCTLarge Human TrialNo Adverse Effects of Medroxyprogesterone Treatment Without Estrogen in Postmenopausal Women: Double-Blind, Placebo-Controlled, Crossover Trial
Medroxyprogesterone treatment alone does not cause adverse symptoms in postmenopausal women, and it cannot explain the side effects reported by women taking combined hormones.
RCT