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.
Reference: FDA Prescribing Information
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