Depo-Provera Side Effects
Generic Name: medroxyprogesterone
Note: This page contains information about the side effects of medroxyprogesterone. Some of the dosage forms included on this document may not apply to the brand name Depo-Provera.
Not all side effects for Depo-Provera may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
For the Consumer
Applies to medroxyprogesterone: oral tablet
Other dosage forms:
In addition to its needed effects, some unwanted effects may be caused by medroxyprogesterone (the active ingredient contained in Depo-Provera). In the event that any of these side effects do occur, they may require medical attention.
You should check with your doctor immediately if any of these side effects occur when taking medroxyprogesterone:Incidence not known
- Abdominal or stomach pain
- absent, missed, or irregular menstrual periods
- blurred vision
- breast pain or tenderness
- changes in skin color
- clay-colored stools
- dark urine
- decrease in amount of urine
- difficulty swallowing
- dizziness or lightheadedness
- eye pain
- fast heartbeat
- hives or welts, itching, redness, swelling, or skin rash
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- loss of appetite
- menstrual changes
- noisy, rattling breathing
- pain in the chest, groin, or legs, especially the calves
- pain, tenderness, or swelling of the foot or leg
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- severe, sudden headache
- shortness of breath
- slurred speech
- stopping of menstrual bleeding
- sudden loss of coordination
- sudden, severe weakness or numbness in the arm or leg
- sudden, unexplained shortness of breath
- swelling of the fingers, hands, feet, or lower legs
- troubled breathing at rest
- unexpected or excess milk flow from the breasts
- unpleasant breath odor
- unusual tiredness or weakness
- vaginal bleeding or spotting
- vision changes
- vomiting of blood
- weight gain
- yellow eyes or skin
Some of the side effects that can occur with medroxyprogesterone may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:Incidence not known
- Blemishes on the skin
- feeling sad or empty
- hair loss, thinning of hair
- increased hair growth, especially on the face
- lack of appetite
- loss of interest or pleasure
- sleepiness or unusual drowsiness
- trouble concentrating
- trouble sleeping
- weight changes
For Healthcare Professionals
Applies to medroxyprogesterone: compounding powder, intramuscular suspension, oral tablet, subcutaneous suspension
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 Depo-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]
Weight gain is more frequently encountered than weight loss during medroxyprogesterone (the active ingredient contained in Depo-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 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 Depo-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]
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 Depo-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]
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 Depo-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 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 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 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 side effects have occurred in up to 5% of patients and included nausea, abdominal pain, bloating, and anorexia.[Ref]
Hepatic side effects have included elevations in liver function tests, jaundice, cholestatic jaundice, and cholelithiasis.[Ref]
Hematologic side effects have included rare reports of hypercoagulability with and without thromboembolic activity.[Ref]
Hypersensitivity side effects have been uncommon but have included urticaria, angioneurotic edema, and anaphylaxis or anaphylactoid reactions.[Ref]
Local side effects associated with intramuscular administration of medroxyprogesterone (the active ingredient contained in Depo-Provera) have included pain, change in skin color, residual lumps, and sterile abscesses at the injection site.[Ref]
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 side effects have included dysphoric symptoms similar to premenstrual syndrome (PMS).[Ref]
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