E-Case 3-B

Christopher H. Smith, M.D.

June 25-29, 2001

Forty-seven year-old woman with a several month history of insomnia, irritability and irregular menses (occasionally missed, late and heavy) sees you for advice.  She wonders about the need for supplemental estrogen.  "My sister felt this way at 45, and when she started hormones, everything got better."  At the same time she expresses some reservations about the side effects of HRT; two of her friends have recently been diagnosed with breast cancer.  Apart from the above noted symptoms she feels well without fatigue, headaches, fevers, palpitations, weight loss or easy bruisablity.

PMH: nephrolithiasis 1984, GERD

Meds: Zantac PRN

Exam shows normal affect and alertness, normal pelvic exam without genital tract lesions, normal uterine size and position.

How would you proceed?

• Diagnosis of perimenopause is likely given constellation of symptoms, patient age and timing of sister's menopause onset.  Should also consider hyperthyroidism, depression, sleep disorder, pregnancy and hematologic conditions (thrombocytopenia).

• Treatment with estrogen supplementation might help to confirm your suspicion of estrogen deficiency if clinical improvement occurs.  At this stage (perimenopause), low dose oral contraceptives might be the best option, even if contraception is not an issue.  Low dose OCPs (such as Loestrin 1/20, Alesse, Mircette or Levlite) contain 20 mcg of estrogen rather than 30-50 mcg found in some other OCPs.  In addition to relieving perimenopausal symptoms and preventing pregnancy, they decrease bone loss and reduce the risk of endometrial and ovarian cancer.  They shouldn't be used in women over 35 years of age who smoke, have uncontrolled hypertension or a history of thrombotic disease.

• If menopausal symptoms are a problem during the placebo week, you can suggest continuous administration of active OCP or an estrogen patch just during that week of the month.

• An alternative to low dose OCPs would be cyclical medroxyprogesterone (Provera), 10 mg QD for 10 days each month, to regulate cycles.  This does not relieve the other symptoms of perimenopause however.

• If this patient had had recurrent early or more frequent bleeding (cycle lengths less than 21 days or intermenstrual bleeding) some gynecologists would recommend endometrial aspiration prior to hormonal Rx to rule out endometrial hyperplasia or carcinoma.

In this case the patient found treatment with Loestrin to be very helpful in alleviating her symptoms and making menses lighter and more predictable.  However after two years she asks about changing to HRT.  She remains concerned about the risk for breast cancer with estrogen supplementation, but also acknowledges that osteoporosis runs in her family.  She has no significant CAD risks.

There are really two questions here: When should you switch from low dose OCPs to standard HRT, and is HRT indicated in this woman?

• Because OCPs contain 4 to 10 times the estrogen activity of Premarin, it is desirable to make this switch when possible.  Determining the right time can be challenging.  Switching too soon may put your sexually active patients at risk for unwanted pregnancy.  Some recommend checking both FSH and estradiol serum levels when patients are on the seventh day of their OCP placebo.  Menopause is confirmed by estradiol levels less than 20-30 picogms/ml and FSH > 30 IU/L, however there is quite a lot of day to day variation in these hormones, so such testing is not always reliable.  Others simply recommend going to the lower dose estrogen (Premarin) when menopausal symptoms appear to have abated.

• Recall that progesterone must be given as well to women who still have a uterus to prevent unbalanced (unopposed) stimulation of the endometrium.  There are numerous appropriate regimens and hormone combinations, including continuous or cyclical Rx.

• The decision to use long-term HRT in postmenopausal women is a difficult one, and the evidence guiding risk-benefit discussions is constantly being updated.  I won't get into this in detail, but will say that the most significant benefits are increasing bone density and reduction of cardiovascular risk factors (primarily beneficial effects on lipid profiles).  HRT has not yet been demonstrated to prevent coronary artery disease in a RCT, and may actually promote the occurrence of coronary events in women with a history of CAD.  In weighing an individual woman's options, it is often helpful to check bone density with DEXA.

• If your patient chooses not to go onto long-term therapy, it is best to taper the perimenopausal estrogen supplementation gradually to minimize the frequency of estrogen withdrawal symptoms.  Note that these may occur even years after menopause.

References to follow.