This page discusses HRT regimens, progesterone intolerance, cyclic therapy, continuous combined therapy, premarin, aygestin, and prometrium.
The defining difference between HRT regimens for women with and without a uterus is the need to give progesterone (progestin) when the uterus is present. For this reason, HRT regimens for women who have had a hysterectomy are less complex and avoid the symptoms of progesterone intolerance experienced by many women.
Approximately 30-40% of women who take progesterone experience unpleasant PMS-like symptoms which can range from mild to severe such as moodiness, irritably, breast tenderness and muscle aches. Individuals who had significant premenstrual symptoms while they were premenopausal are more likely to be affected. Progestins produce moodiness and irritability by affecting specific sites in the brain. Changing the type of progesterone, the dose, the route of administration, and the length of treatment can lessen this effect. Forms of natural progesterone given by either the oral or vaginal route may be less of a problem than synthetic progestins. But some patients are so sensitive to the effects of progesterone that they continue to have significant problems and just feel miserable. It is one of the most challenging aspects of caring for the postmenopausal woman. A few physicians are vigorous in their suggestion that natural progesterone cream as sole therapy is a miracle treatment for the postmenopausal woman. However, a careful and responsible analysis of accepted medical literature and investigations does not support this view.
Women with a Uterus
HRT methods for women who have not had a hysterectomy fall into two categories: cyclic, where progesterone is given for part of the month, and continuous combined therapy (CCT), where it is given daily.
Cyclic therapy usually consists of the daily administration of estrogen, usually in the form of an oral estrogen tablet or a transdermal estrogen patch replaced once or twice weekly but worn continually, plus progesterone in tablet form taken 10-12 days a month. Estrogen stimulates and thickens the endometrium (the lining of the uterus) and then progesterone, which has antiestrogenic effects blocks the estrogen stimulation. Progesterone both shrinks the uterine lining and prevents the development of abnormal changes.
Alternatively, the route of administration of the estrogen can be sublingual, transdermal gel or subcutaneous implantation. The route of administration of the progesterone can include sublingual tablets and vaginal suppositories. If this works the way it’s supposed to, 2-5 days after finishing the progesterone the patient experiences “scheduled withdrawal bleeding,” which usually lasts from 3 to 5 days. And this “cycle” is repeated monthly. If the bleeding occurs at any other time during the month it is called “unscheduled bleeding” and signals the need to determine if any overgrowth or abnormal change of the uterine lining is present.
Continuous Combined Therapy
Continuous combined therapy usually consists of a daily estrogen tablet or a transdermal estrogen patch worn as above, plus a smaller dose of progesterone taken daily. The purported benefit of this regimen is that in the majority of cases daily progesterone even in small doses keeps the uterine lining thin and no bleeding occurs. Menstrual bleeding is a very unattractive prospect for many postmenopausal women.
Some common oral estrogen and progesterone combinations. For years, the most frequently prescribed combination consisted of conjugated equine estrogen tablets (brand name Premarin) and medroxyprogesterone acetate (MPA) tablets (brand name Provera). The conjugated equine estrogen (CEE) or Premarin in earlier years was usually given in a dose of 1.25 mg daily on the 1-25th days of the month and the Provera was given the 16-25th days of the month. Nothing was given from the 17th to the end of the month, at which time the cycle was repeated. Many women experienced symptoms such as hot flashes or sweats during the time they were off the estrogen. In more recent years, the CEE is most commonly every day instead of the 1-25th. The dose of CEE in most HRT regimens is usually lower and is most frequently .625 mg. I have found that most of the time if a patient’s symptoms are not alleviated by this dose, that higher doses are no more effective and another product or route of administration might be more effective. The MPA is usually given in a dosage of 10mg for 10-12 days a month. Some physicians give the MPA in a lower dose such as 5mg or every 2nd or 3rd month to decrease the incidence of PMS-like effects, but this is a trade-off you must be aware of as the protection of the uterine is lessened.
In more recent years, additional formulations of estrogen and progesterone were developed and are often substituted in this regimen. Micronized estradiol brand name Estrace is from a plant source and has the hypothetical advantage of actually being estradiol the bioactive form of estrogen although it is altered during intestinal absorption as any other oral preparation would be. Some other brands of oral estrogen preparations include Ogen and Estratab.
Norethindrone acetate (brand name Aygestin) and oral micronized progesterone (brand name Prometrium) are both commonly used forms of oral progesterone replacement. Aygestin is more potent in its ability to shrink the lining of the uterus and is useful as an alternative to MPA when heavy or “unscheduled bleeding” is a problem. It is available as a 5 mg tablet and can be given in doses ranging from 1/4 of a tablet to 2 tablets 10-12 days a month according to each individual’s needs. Prometrium seems to cause less PMS-like effects in women who are sensitive to progestins. It is distributed in 100 mg tablets and is usually given in a dose of 2 tablets at bedtime for 10-12 days a month.