Bleeding While on Hormone Replacement
Frederick R. Jelovsek MD
"Is it normal for a woman on Natural Hormone Replacement (from a compounding pharmacy) to experience a period after 2 and one-half months on the NHR? I have not had a "real" period for 2 years. Can hormones initiate ovulation AGAIN??
I am 50, post menopausal, history of normal periods. The only other medication I take is Lipitor 10mg. Excellent health. Normal weight."
A woman who starts on hormonal replacement therapy (HRT) after the menopause can have bleeding on any hormonal regimen, natural or not. As far as studies go, there do not seem to be differences in the incidence or amount of bleeding depending on what type of HRT is used. It only varies by the relative doses of the estrogens and progesterone/progestin and by whether those ingredients are both taken every day continuously or in a cyclical fashion with the estrogen every day and the progesterone/progestin for two weeks out of four.
Why do women have bleeding while on hormonal replacement therapy?
Most women have some bleeding in the first three months on HRT. It is the rule rather than the exception. The main reasons for bleeding are: too much endometrial tissue stimulated by estrogen or too thin a lining (atrophic) due to too high a progesterone effect. There is a third possibility and that is that there is abnormal tissue inside the uterus like a polyp, premalignant hyperplasia or even a cancer.Bleeding during the first three months of HRT is usually attributed to a hormonal cause. Bleeding after that needs to be investigated to make sure there is not a malignancy.
On a continuous hormonal regimen, only about 2/3's of women stop bleeding at all by 6 months. By one year almost 80% of women will have no bleeding on oral medications and over 85% on transdermal combined therapy (1). If women take HRT cyclically, they usually have some withdrawal bleeding each month. Thus a cyclical regimen makes bleeding more predictable but you still have regular menses.
Can hormone replacement cause a woman to ovulate again?
Rarely, estrogen can induce ovulation in women who have ovarian failure and are menopausal. We do not know how often it occurs and most studies about this have been performed on women who had a premature menopause (below age 40) and not on women undergoing natural menopause in the late 40's and early 50's (2). When women with premature menopause underwent a randomized clinical trial in which some were prescribed estrogens and the others placebo, ovulation was induced in 46% of those women although only 25% of women who had been amenorrheic more than 3 months ovulated (3). Certainly the incidence of ovulation must go down as a woman is further removed in time from stopping menses but we do not know what the time period is to absolutely no ovulations induced by HRT. I would guess that at age 50 and being 2 years post menopause would make ovulation very rare indeed.
What can be done to stop the bleeding on hormone replacement?
A bleeding side effect from HRT is the most common cause for discontinuance (4). It was the primary reason for stopping in 52% of women over 65 and 29% of younger women age 50-55.
To minimize the bleeding if it persists beyond 3 months of starting therapy and an endometrial biopsy or some type of sampling of the endometrium has been performed to rule out cancer or premalignant hyperplasia, the doses of estrogen and progesterone/progestin must be altered. Sometimes the solution is to lower the estrogen level and other times the solution is to raise the progesterone/progestin level. Again, it does not matter if the hormone therapy is "natural" or other types of estrogens and progestins.
A general rule of thumb is to raise the progesterone dose if it is low (e.g., 2.5 mg medroxyprogesterone acetate, 100 mg micronized progesterone (natural)) and the estrogen dose is medium or above (0.625 - 1.25mg conjugated estrogen, 1 - 2 mg estradiol). If a woman has mood symptoms from too much progesterone (irritability, feeling poorly) then is is better to lower the estrogen dose. Admittedly, the real difficulty comes when the doses are changed to control the bleeding. and because of the change, a woman has other hormonal side effects:
estrogens get too low
- hot flashes
- night sweats, difficulty sleeping
- depression, teariness
- vaginal dryness
progesterone/progestins get too high
- feel poorly
What is the best regimen for menopausal hormonal replacement to minimize bleeding?
Most women choose to take continuous HRT (estrogen and progesterone/progestin every day) if they have not had a hysterectomy because they do not desire to have menstrual periods. Since women who are closer to menopause often need higher doses of estrogen to control hot flashes and sleep disturbances, they will also need a proportionately higher progesterone/progestin level.
Regimens that I have found useful for menopausal women who have not had a hysterectomy are:
Women ages 45-55 and within 6 months of beginning menopausal symptoms or women having moderate to severe estrogen deficiency symptoms
- conjugated estrogens 1.25 mg, medroxyprogesterone acetate 5 mg
- micronized estradiol 2 mg, micronized progesterone 200 mg (natural HRT)
- transdermal (skin patch) estradiol 0.1 mg/day, norethindrone acetate 1 mg (orally)
Women ages 55-65 or 45-55 and not having many estrogen deficiency symptoms
- conjugated estrogens .625 mg, medroxyprogesterone acetate 2.5 mg
- micronized estradiol 1 mg, micronized progesterone 100 mg (natural HRT)
- transdermal (skin patch) estradiol 0.05 mg/day, norethindrone acetate 140 mg
Women ages 65-80
- conjugated estrogens .3 mg, medroxyprogesterone acetate 2.5 mg
- micronized estradiol 0.5 mg, micronized progesterone 100 mg (natural HRT)
Doses are then regulated up or down depending upon bleeding, other side effects and sometimes body size because heavy women may have more endogenous estrogens that need to be countered with higher progestin doses.