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Progesterone use in management of secondary amenorrhea
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Expiration date: July 31, 2009
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Target: Physicians, physician assistants and nurse practitioners
Supported by an educational grant from Solvay Pharmaceuticals, Inc.
Sponsored by the American Society for Reproductive Medicine.
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Nicole is 27 years old, gravida 0, with a long history of obesity and great difficulty losing weight. She reports having irregular menstrual cycles ranging from 45 days to 6 months apart. Her last menstrual period was 5 months ago, when she had a heavy menses that lasted 2 weeks. Her body mass index is 42 kg/m2, which is considered morbid obesity. Nicole has a large abdominal pannus and normal blood pressure. She has scattered acne lesions on her face and upper back and acanthosis nigricans, a dark pigmentation around the neck and the axilla. Acanthosis nigricans is a biomarker for insulin resistance and high circulating insulin levels.
Nicole’s pelvic exam showed a normal vagina and cervix, but it was not possible to palpate her uterus or ovaries because of her abdominal girth. Transvaginal ultrasound found an endometrial thickness of 22 mm. Her ovaries appeared to be multicystic but had normal ovarian volumes. We performed an endometrial biopsy because of concerns about the long duration of unopposed estrogen exposure. The biopsy revealed complex hyperplasia with no atypia.
A lipid profile demonstrated cholesterol 245 mg/dL low-density lipoprotein cholesterol of 180 mg/dL and triglyceride levels of 259 mg/dL. This patient demonstrates many features we see with increasing frequency in reproductive-aged women as we deal with the obesity epidemic.
A complicated diagnosis
Nicole’s abdominal obesity, high triglycerides, and evidence of insulin-resistance constituted metabolic syndrome. Although there are many different criteria for this, we used those of the National Cholesterol Education Program (TABLE).1
Components of Metabolic Syndrome
Related to Cardiovascular Disease
Source: Grundy SM, et al. Circulation. 2002;106:3143-3421.
If she is not treated, Nicole would be unable to achieve pregnancy because she does not ovulate and she may have an increased risk of endometrial cancer. Her obesity would eventually cause increasing insulin levels, exhaustion of her pancreatic insulin secretion, and type 2 diabetes. Her obesity might also result in osteoarthritis and difficulty with mobility. Her lipid levels confer increased risk of hypertension and cardiovascular events.
Selecting a treatment strategy: Considerations
If this patient does not desire pregnancy, short-term treatment for endometrial hyperplasia involves administration of progesterone or progestins for at least 2 weeks per month for 3 months, with a follow-up endometrial biopsy.
Nicole also needs protection against endometrial hyperplasia even after this episode is addressed. Oral contraceptives are frequently used for long-term treatment, although there might be concern about the risk of deep vein thrombosis (DVT), particularly in obese or morbidly obese patients and older patients who smoke.
If this patient were not a candidate for oral contraceptives, progesterone or a progestin would typically be administered for approximately 2 weeks each month to prevent recurrence of the hyperplasia. Patients who do not desire a monthly withdrawal bleed can take progesterone every 2 to 3 months. Patients who are being treated with a progestogen for amenorrhea and hyperplasia may occasionally ovulate. They should be counseled that an alternative form of contraception, such as condoms, is needed to avoid pregnancy.
An intrauterine device (IUD) for this patient could also be considered for this patient. We have individual patients using a levonorgestrel-containing IUD. One challenge we have faced with some of our obese patients is difficultly accessing the cervix for placement.
Case study follow-up
Nicole received norethindrone,2,3 5 mg, a strong progestin, for 2 weeks and had a withdrawal flow for 3 months in a row. Her repeat endometrial biopsy showed a normal endometrium. She still did not ovulate, and since she was not sexually active at that time, she elected to use progesterone, 200 mg, for 14 days every 2 months. We treated her acne with topical clindamycin gel and she joined our supervised diet and exercise program. She is considering bariatric surgery but must participate in the lifestyle program for at least 6 months in order to qualify.