Provera Side Effects

Generic Name: medroxyprogesterone

Note: This page contains side effects data for the generic drug medroxyprogesterone. It is possible that some of the dosage forms included below may not apply to the brand name Provera.

It is possible that some side effects of Provera may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to medroxyprogesterone: intramuscular injectable, intramuscular suspension

As well as its needed effects, medroxyprogesterone (the active ingredient contained in Provera) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking medroxyprogesterone, check with your doctor or nurse immediately:

More common
  • Absent, missed, or irregular menstrual periods
  • menstrual changes
  • stopping of menstrual bleeding
Less common
  • Breast pain
  • cramps
  • heavy bleeding
  • increased clear or white vaginal discharge
  • itching of the vagina or genital area
  • pain during sexual intercourse
  • swelling
  • thick, white vaginal discharge with no odor or with a mild odor
Incidence not known
  • Abdominal or stomach pain
  • anxiety
  • black, tarry stools
  • blood in the stools
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • changes in skin color
  • chest pain
  • chills
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • cough
  • dark urine
  • decrease in height
  • difficult or labored breathing
  • difficulty with breathing
  • difficulty with swallowing
  • dimpling of the breast skin
  • dizziness or lightheadedness
  • dull ache or feeling of pressure or heaviness in the legs
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • fever
  • headache
  • hives
  • increased thirst
  • inverted nipple
  • itching
  • itching skin near damaged veins
  • loss of appetite
  • lump in the breast or under the arm
  • nausea
  • no sensation in the legs
  • noisy breathing
  • pain in the back, ribs, arms, or legs
  • pain, redness, tenderness, or swelling of the arm, foot, or leg
  • pale skin
  • persistent crusting or scaling of the nipple
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rash
  • redness or swelling of the breast
  • shortness of breath
  • skin rash
  • sore on the skin of the breast that does not heal
  • sudden shortness of breath or troubled breathing
  • swollen feet and ankles
  • tightness in the chest
  • troubled breathing with exertion
  • unable to move the legs
  • unpleasant breath odor
  • unusual bruising or bleeding
  • unusual tiredness or weakness
  • vomiting of blood
  • wheezing
  • yellow eyes or skin

Some medroxyprogesterone side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Abdominal or stomach discomfort
  • decreased interest in sexual intercourse
  • inability to have or keep an erection
  • increased weight
  • loss in sexual ability, desire, drive, or performance
  • nervousness
Less common
  • Backache
  • blemishes on the skin
  • bloating
  • depression
  • difficulty with moving
  • feeling of warmth
  • hair loss or thinning of the hair
  • lack or loss of strength
  • leg cramps
  • muscle pain or stiffness
  • pain in the joints
  • pimples
  • redness of the face, neck, arms, and occasionally, upper chest
  • sleeplessness
  • sudden sweating
  • trouble sleeping
  • unable to sleep
Incidence not known
  • Brown, blotchy spots on the exposed skin
  • changes in appetite
  • diarrhea
  • drowsiness
  • dry skin
  • hoarseness
  • increased hair growth, especially on the face
  • increased in sexual ability, desire, drive, or performance
  • increased interest in sexual intercourse
  • increased sweating and body odor
  • indigestion
  • loss of appetite
  • pain at the injection site
  • passing of gas
  • patchy brown or dark brown discoloration of the skin
  • stomach pain, fullness, or discomfort
  • swelling of the armpits
  • unexpected or excess milk flow from breasts

For Healthcare Professionals

Applies to medroxyprogesterone: compounding powder, intramuscular suspension, oral tablet, subcutaneous suspension

Endocrine

Cushing's syndrome is uncommon and appears to be associated with a long duration of therapy and moderate to high doses of medroxyprogesterone (the active ingredient contained in Provera) Doses used for hormonal replacement therapy and for long-term contraception are not associated with Cushing's syndrome.

Medroxyprogesterone has mild glucocorticoid activity. In cases of medroxyprogesterone-induced Cushing's syndrome, low cortisol and adrenocorticotrophic hormone (ACTH) levels with a reduced pituitary-adrenal reserve have been documented. Acute adrenal insufficiency may ensue following withdrawal of medroxyprogesterone.[Ref]

Endocrine side effects have included breast tenderness, galactorrhea with or without hyperprolactinemia, prevention of lactation, hirsutism, and Cushing's syndrome.[Ref]

Metabolic

Weight gain is more frequently encountered than weight loss during medroxyprogesterone (the active ingredient contained in Provera) therapy. In women using intramuscular medroxyprogesterone for contraception, the mean weight gain after one year of therapy is 2.5 kg. After two, four, and six years, patients gain a mean of 3.7, 6.3, and 7.5 kg, respectively.

Data regarding the effect of medroxyprogesterone on lipid profiles have been conflicting. Some studies report possible negative effects on lipid profiles while others have documented a reduction in total and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol levels.[Ref]

Metabolic side effects have included weight changes (increases and decreases), glucose intolerance, and changes in serum cholesterol concentrations.[Ref]

Genitourinary

Genitourinary side effects have been relatively common and included primarily menstrual changes such as amenorrhea, irregular bleeding, spotting, and heavy bleeding. Vaginal cysts, dyspareunia, and changes in cervical erosion and secretions have also been reported. While endometrial hyperplasia has been reported, medroxyprogesterone (the active ingredient contained in Provera) tended to have a favorable effect on the endometrium. Changes in libido and anorgasmia have also occurred.[Ref]

Withdrawal bleeding is a common complaint among postmenopausal women receiving sequential (10 to 14 days per cycle) medroxyprogesterone therapy. In postmenopausal women receiving continuous medroxyprogesterone and estrogen therapy, 75% or more are amenorrheic by one year of therapy.

In women receiving medroxyprogesterone for contraception, more than 50% are amenorrheic by one year of therapy.

In women on estrogen replacement therapy, the addition of medroxyprogesterone or other progestin for at least 10 to 14 days of each cycle significantly reduces the risk of endometrial hyperplasia and, thus, the risk of endometrial carcinoma. Low-dose continuous medroxyprogesterone therapy also reduces the risk of endometrial hyperplasia associated with the use of unopposed estrogen.

In patients in whom abnormal bleeding persists or is severe, the possibility of an organic pathology should be considered and ruled out.[Ref]

Oncologic

A significant increase in the incidence of breast cancer in beagle dogs in addition to an apparent increase in the incidence of endometrial cancer in rhesus monkeys was noted in early animal carcinogenicity studies.

International long-term studies designed to assess the risk of medroxyprogesterone (the active ingredient contained in Provera) in humans, sponsored by the World Health Organization, failed to find an increased risk of cancer in users of medroxyprogesterone. Overall, there was no significant increase in the risk of breast cancer, cervical cancer, or epithelial ovarian cancer. Data from these studies did, however, support a significant (8-fold) reduction in the incidence of endometrial cancer among medroxyprogesterone users.

A study from New Zealand has suggested that women taking depot medroxyprogesterone acetate may be at higher risk for breast cancer during the first 5 years, but therapy for more than 5 years confers no increased risk of breast cancer.[Ref]

Oncologic side effects possibly associated with medroxyprogesterone have been the topic of considerable debate. Data from some animal studies suggested an increased risk of breast and endometrial cancer. The current consensus is that the carcinogenic potential of medroxyprogesterone is no greater than that of other hormonal contraceptives.[Ref]

Cardiovascular

The majority of cases of thromboembolic disease during hormonal therapy have been attributed to estrogens and not to progestins. However, it has been demonstrated that medroxyprogesterone (the active ingredient contained in Provera) at least at high doses, can produce a hypercoagulable state. Whether or not this contributes to the development of thrombotic events remains unknown.

Because medroxyprogesterone can cause edema, it should be used cautiously in patients with underlying disease (like migraine headaches, asthma, heart disease, renal dysfunction, or seizure disorders) which may be exacerbated by edema or fluid retention.[Ref]

Cardiovascular side effects have included thromboembolic disorders such as thrombophlebitis, deep vein thrombosis, pulmonary embolism, cerebrovascular accidents, and retinal thrombosis. In addition, edema, hypertension, tachycardia, and syncope have been noted.[Ref]

Musculoskeletal

Musculoskeletal side effects have included changes in bone mineral density and leg cramps.[Ref]

Reductions in bone mineral density and osteoporosis have been attributed to medroxyprogesterone. Such effects are probably due to medroxyprogesterone-induced estrogen deficiency.

Conflicting data concerning the effects of medroxyprogesterone on bone mineral density have been reported.

In one study, women 25 to 51 years of age receiving medroxyprogesterone 150 mg intramuscularly every three months for five or more years for long-term contraception had a reduction in bone mineral density compared with premenopausal controls. However, bone mineral density in the treatment group was still significantly greater than that observed in postmenopausal controls.

A study of 200 women who received medroxyprogesterone 150 mg intramuscularly every three months for a median duration of 12 years (range 2 to 26 years) reported that bone density was significantly reduced in medroxyprogesterone users. However, bone mineral density in women starting depot medroxyprogesterone after the age of 20 years and using it for 15 or fewer years was greater than the remainder of the cohort.

A study to determine the potential for postmenopausal fracture due to residual effects of depot medroxyprogesterone in former users reported the risk to be small and unlikely to have substantial impact in postmenopausal women. No significant differences in bone density were found, however, women who had used depot medroxyprogesterone for >2 yeas had a trend toward lower bone densities.

Bone density in 185 women receiving long-term depot medroxyprogesterone for a mean of 5 years (range of 1-16 years) was only minimally below the normal population despite decreased estrogen levels.[Ref]

Dermatologic

Dermatologic side effects have included acne, reduced hair growth, alopecia, melasma, chloasma, rash, excessive sweating, dry skin, scleroderma, erythema multiforme, and erythema nodosum.[Ref]

Nervous system

Nervous system side effects have included headache, asthenia, dizziness, depression, somnolence, and insomnia. Paresthesias, convulsions, and facial palsy have been reported although causality is unknown.[Ref]

Gastrointestinal

Gastrointestinal side effects have occurred in up to 5% of patients and included nausea, abdominal pain, bloating, and anorexia.[Ref]

Hepatic

Hepatic side effects have included elevations in liver function tests, jaundice, cholestatic jaundice, and cholelithiasis.[Ref]

Hematologic

Hematologic side effects have included rare reports of hypercoagulability with and without thromboembolic activity.[Ref]

Hypersensitivity

Hypersensitivity side effects have been uncommon but have included urticaria, angioneurotic edema, and anaphylaxis or anaphylactoid reactions.[Ref]

Local

Local side effects associated with intramuscular administration of medroxyprogesterone (the active ingredient contained in Provera) have included pain, change in skin color, residual lumps, and sterile abscesses at the injection site.[Ref]

Ocular

Ocular side effects have included visual disturbances such as sudden loss of vision (partial or complete), sudden onset of proptosis, diplopia, or migraine have been reported. Therapy should be withdrawn in the presence of papilledema or retinal vascular lesions.[Ref]

Psychiatric

Psychiatric side effects have included dysphoric symptoms similar to premenstrual syndrome (PMS).[Ref]

References

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