Does Depo-Provera (medroxyprogesterone) cause side effects?
Depo-Provera (medroxyprogesterone) contains a derivative of the naturally occurring female progestin, progesterone used to treat missed menstrual periods (amenorrhea), abnormal uterine bleeding, endometrial cancer, and renal cancer.
Progestins are responsible for changes in the mucus and inner lining of the uterus (endometrium) during the second half (secretory phase) of the menstrual cycle. Progestins prepare the endometrium for implantation of the embryo.
Once an embryo implants in the endometrium and pregnancy occurs, progestins help maintain the pregnancy. At high doses, progestins can prevent ovulation (release of the egg from the ovary) and thereby prevent pregnancy.
Common side effects of Depo-Provera include
- breast tenderness,
- leakage of liquid from the nipple,
- skin reactions (hives, acne, hair growth, and hair loss),
- break-through bleeding (menstrual-like bleeding in the middle of the menstrual cycle),
- vaginal spotting of blood,
- changes in menstrual flow,
- changes in weight,
- insomnia, and
- yellowing skin and eyes (jaundice).
Serious side effects of Depo-Provera include blood clots and difficulty controlling blood glucose in diabetic patients.
Drug interactions of Depo-Provera include aminoglutethimide, because it may increase the elimination of Depo-Provera by the liver leading to a decrease in the concentration of Depo-Provera in blood and possibly a reduction in the effectiveness of the Depo-Provera. Depo-Provera inhibits fertility at high doses. It should not be given during pregnancy.
What are the important side effects of Depo-Provera (medroxyprogesterone)?
Breast tenderness and leakage of liquid from the nipple occur rarely with medroxyprogesterone. Various skin reactions, including hives, acne, hair growth and hair loss, also have been reported occasionally. Break-through bleeding (menstrual-like bleeding in the middle of the menstrual cycle), vaginal spotting of blood, changes in menstrual flow, increased or decreased weight, nausea, fever, insomnia, and jaundice have all been reported.
Blood clots are an occasional serious side effect of progestin therapy, and cigarette smokers are at a higher risk for clots. Therefore, females requiring progestin therapy are strongly encouraged to quit smoking.
People with diabetes may experience difficulty controlling blood glucose when taking medroxyprogesterone for unclear reasons. Therefore, increased monitoring of blood sugar and adjustment of medications for diabetes is recommended.
The Women's Health Initiative (WHI) study found an increased risk of heart attacks, stroke, breast cancer, blood clots, and pulmonary emboli (blood clots that lodge in the lungs) in postmenopausal women (50 to 79 years of age) who took medroxyprogesterone in combination with estrogens for 5 years, as well as an increased risk of dementia in the women over age 65.
Therefore, medroxyprogesterone should not be used for the prevention of heart disease or dementia. Although medroxyprogesterone alone has not been demonstrated to promote breast cancer, since breast cancer has progesterone receptors, physicians usually avoid using progestins in women who have had breast cancer.
Depo-Provera (medroxyprogesterone) side effects list for healthcare professionals
See prescribing information for possible adverse effects on the fetus.
Reproductive System And Breast Disorders
- breakthrough bleeding
- change in menstrual flow
- changes in cervical erosion and cervical secretions
- breast tenderness and galactorrhea
- erectile dysfunction
Nervous System Disorders
General Disorders And Administration Site Conditions
- injection site reaction, injection site pain/tenderness, injection site persistent atrophy/indentation/dimpling, lipodystrophy acquired, injection site nodule/lump
In a few instances there have been undesirable sequelae at the site of injection, such as residual lump, change in color of skin, or sterile abscess.
- change in weight (increase or decrease)
- cholestatic jaundice, including neonatal jaundice
Skin And Subcutaneous Tissue Disorders
- skin sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash
- acne, alopecia and hirsutism
- rash (allergic) with and without pruritis
Immune System Disorders
- corticoid-like effects (e.g., Cushingoid syndrome)
Metabolism And Nutrition Disorders
A statistically significant association has been demonstrated between use of estrogen-progestin combination drugs and pulmonary embolism and cerebral thrombosis and embolism. For this reason patients on progestin therapy should be carefully observed. There is also evidence suggestive of an association with neuro-ocular lesions, e.g. retinal thrombosis and optic neuritis.
The following adverse reactions have been observed in patients receiving estrogenprogestin combination drugs:
- rise in blood pressure in susceptible individuals
- premenstrual syndrome
- changes in libido
- changes in appetite
- cystitis-like syndrome
- loss of scalp hair
- erythema multiforma
- erythema nodosum
- hemorrhagic eruption
The following laboratory results may be altered by the use of estrogen-progestin combination drugs:
- increased sulfobromophthalein retention and other hepatic function tests
- coagulation tests: increase in prothrombin factors VII, VIII, IX, and X
- metyrapone test
- pregnanediol determinations
- thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in T3 uptake values
What drugs interact with Depo-Provera (medroxyprogesterone)?
Aminoglutethimide administered concomitantly with Depo-Provera Sterile Aqueous Suspension may significantly depress the serum concentrations of medroxyprogesterone acetate. Depo-Provera users should be warned of the possibility of decreased efficacy with the use of this or any related drugs.
Medroxyprogesterone acetate is metabolized primarily by hydroxylation via the CYP3A4. Though no formal drug interaction trials have been conducted, concomitant administration of strong CYP3A inhibitors is expected to increase concentrations of medroxyprogesterone acetate, whereas the concomitant administration of strong CYP3A inducers is expected to decrease medroxyprogesterone acetate concentrations.
Therefore, coadministration with strong CYP3A inhibitors, including the following should be avoided:
- voriconazole, or
- strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort).
Laboratory Test Interactions
The pathologist should be advised of progestin therapy when relevant specimens are submitted. The following laboratory tests may be affected by progestins including Depo-Provera Sterile Aqueous Suspension:
- Plasma and urinary steroid levels are decreased (e.g. progesterone, estradiol, pregnanediol, testosterone, cortisol).
- Gonadotropin levels are decreased.
- Sex-hormone binding globulin concentrations are decreased.
- Protein bound iodine and butanol extractable protein bound iodine may increase. T3 uptake values may decrease.
- Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X may increase.
- Sulfobromophthalein and other liver function test values may be increased.
- The effects of medroxyprogesterone acetate on lipid metabolism are inconsistent. Both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been observed in studies.
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Related Disease Conditions
Birth Control Options
Birth control is available in a variety of methods and types. The method of birth control varies from person to person, and their preferences to either become pregnant or not. Examples of barrier methods include barrier methods (sponge, spermicides, condoms), hormonal methods (pill, patch), surgical sterilization (tubal ligation, vasectomy), natural methods, and the morning after pill. Side effects and risks of each birth control option should be reviewed prior to using any birth control method.
Which Birth Control Has Least Side Effects?
No form of birth control is free of side effects, but there are some that have the least noticeable ones.
Amenorrhea (including hypothalmic amenorrhea) is a condition in which there is an absence of menstrual periods in a woman. There are two types of amenorrhea: primary and secondary. Treatment of amenorrhea depends on the type. In primary, surgery may be an option and in secondary amenorrhea medication or lifestyle changes may be treatment options. We go over the definition of amenorrhea, causes, and treatment options for amenorrhea.
Birth Control Pill vs. Depo-Provera Shot
Birth control pills (oral contraceptives) and the Depo-Provera shot are two hormonal methods of birth control. Both methods work by changing the hormone levels in your body, which prevents pregnancy, or conception. Differences between "the pill" and "the shot." Birth control pills are available as combination pills, which contain the hormones estrogen and progestin, or mini-pills that only contain progestin. In comparison to the Depo-Provera injection, which prevents pregnancy for three consecutive months. Both methods of birth control are very effective in preventing pregnancy. Both the combination pill (if you take them as directed) and shot are up to 99% effective in preventing pregnancy. While the mini-pill is only about 95% effective in preventing pregnancy. Both methods cause weight gain, and have other similar side effects like breast pain, soreness or tenderness, headaches, and mood changes. They may lead to decreased interest in sex in some women. There are differences between the other side effects of these methods (depending upon the method) that include breakthrough bleeding or spotting, acne, depression, fatigue, and weakness. Both oral contraceptives and the Depo-Provera shot have health risks associated with them, such as, heart attack, stroke, blood clots, and cervical cancer. Birth control pills appear to increase the risk of cervical cancer. Talk with your OB/GYN or other doctor or health care professional about which birth control method is right for you.
DVT and Birth Control Pills (Oral Contraceptives)
Deep vein thrombosis (DVT) is a blood clot that has traveled deep into the veins of the arm, pelvis, or lower extremities. Oral contraceptives or birth control pills can slightly increase a woman's risk for developing blood clots, including DVT. DVT symptoms and signs in the leg include leg or calf pain, redness, swelling, warmth, or leg cramps, and skin discoloration. If a blood clot in the leg is not treated, it can travel to the lungs, which can cause a pulmonary embolism (blood clot in the lung) or post-thrombotic syndrome, both of which can be fatal if not treated immediately. Increased risk factors for DVT and birth control pills include over 40 years of age, family history, smoking, and obesity. Other medical problems that increase the risks of blood clots, for example, lung or heart disease, or inflammatory bowel disease or IBD (Crohn's disease and ulcerative colitis (UC). Other options for preventing pregnancy include IUDs, birth control shots, condoms, diaphragms, and progestin-only oral contraceptives.
Endometrial Cancer Prevention
Endometrial cancer, or uterine cancer, affects the endometrium of the uterus. It's the most common invasive cancer of the female reproductive system. Risk factors include smoking, obesity, lack of exercise, taking estrogen-only hormone therapy, early menstruation, late menopause, and never being pregnant.
What Does Birth Control Do to Your Body?
Different birth control methods work in different manners. No birth control method is perfect and every procedure or method has a side effect.
What Is the Best Form of Birth Control?
What's "best" among birth control methods differs from person to person. What's right for one person may not be right for others. And a person’s needs may also change over time.
Treatment & Diagnosis
Medications & Supplements
- medroxyprogesterone - oral, Provera
- medroxyprogesterone acetate (anticancer agent) - injection, Depo-Provera
- medroxyprogesterone acetate (contraceptive) - intramuscular, Depo-Provera
- Birth Control Pills (Oral Contraceptive) vs. Depo-Provera (medroxyprogesterone injection)
- medroxyprogesterone (Depo-Provera)
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.