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,
  • nausea,
  • fever,
  • 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.

Depo-Provera is secreted in breast milk. The effect on the infant has not been determined. Consult your doctor before breastfeeding.

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
  • spotting
  • change in menstrual flow
  • amenorrhea
  • changes in cervical erosion and cervical secretions
  • breast tenderness and galactorrhea
  • erectile dysfunction
Nervous System Disorders
Psychiatric Disorders
General Disorders And Administration Site Conditions
  • edema
  • pyrexia
  • fatigue
  • malaise
  • 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.

Investigations
  • change in weight (increase or decrease)
Hepatobiliary Disorders
Skin And Subcutaneous Tissue Disorders
Immune System Disorders
Gastrointestinal Disorders
  • nausea
Endocrine 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:

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.

In vitro

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:

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:

  1. Plasma and urinary steroid levels are decreased (e.g. progesterone, estradiol, pregnanediol, testosterone, cortisol).
  2. Gonadotropin levels are decreased.
  3. Sex-hormone binding globulin concentrations are decreased.
  4. Protein bound iodine and butanol extractable protein bound iodine may increase. T3 uptake values may decrease.
  5. Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X may increase.
  6. Sulfobromophthalein and other liver function test values may be increased.
  7. 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.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 9/15/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.