For those women who can assimilate oral estrogen without a problem, the most commonly prescribed dose is 0.625 mg. However, some women need higher doses such as 0.9 mg or 1.25 mg to attain symptom relief. Occasionally, women drop their doses in half to 0.3 mg to avoid side effects, but this dose may not be enough to benefit bones and avoid bone loss. Only trial and error will tell you which dose works best for you. Women who have already had a hysterectomy can take estrogen tablets alone because they obviously have no risk of developing uterine cancer. Women who have an intact uterus should always take a formulation that includes progestin for at least 10 to 13 days of each month for cancer protection.
Transdermal Estrogen
The transdermal system, marketed under the name Estraderm (IBA Pharmaceuticals), was created to avoid the problems inherent in oral estrogen's first pass through the liver. In this innovative system, estrogen is absorbed into the general circulation through a medicated patch on the skin. This method avoids the initial pass through the digestive tract and liver, so women with liver and gallbladder disease are more likely to be able to tolerate ERT. This is also true for women with hypertension and clotting problems, provided clotting factors are normal.
Another benefit is that the patch dispenses estrogen continuously, rather than in one large burst like the tablet. The delivery of estrogen into the body throughout the day and night more closely resembles your body's own estrogen production. Because the body is receiving estrogen on a continuous basis, a woman is less likely to suffer from symptoms which can occur with estrogen pill when hormones are stopped for a week each month.
What does the patch look like? Many women compare it with a small, round, clear Band-Aid that is several inches in size. It is placed on the skin of the abdomen, buttocks or thigh and changed twice a week. Each patch contains a reservoir of estrogen placed in a membrane that releases estrogen at a controlled, standardized level. The nonabsorbent patch allows for greater freedom because it can be kept on while you shower or bathe.
Unlike the estrogen pill, there is not as much flexibility of dosage range. Basically, the transdermal patch is available in two dosages: 0.05 mg and 0.1 mg. Some women find they do not tolerate these dosages well and develop side effects. A new transdermal patch called Vivelle, manufactured by Ciba Pharmaceuticals, may solve this problem for some women. It will be available in four dosages from 0.0375 mg to .1 mg and has been scheduled for consumer use in the fall of 1995. To decrease the amount of hormone released from the patch, part of the backing can be occluded by a small piece of ordinary adhesive bandage. This reduces the total surface area of the skin exposed to the hormone. Some women prefer to use oral estrogen because it is less expensive than the patch. Finally, ten percent of all patch users develop skin irritation from the patch's adhesive. To reduce the likelihood and severity of the skin reaction, apply the patch on different areas of your skin. The buttocks area seems to tolerate the patch best. Be sure to wait at least a week before reusing a prior site. During times of acute irritation, you can change the patch more frequently, every 12 to 24 hours; if needed, talk to your doctor about ways to relieve skin irritation. You may also want to remove the patch before swimming or soaking in a hot tub and reapply it once you have dried your skin.
As with oral estrogen, the patch is used in conjunction with progesterone if the woman still has an intact uterus, and progesterone should be taken for the recommended number of days each month. The patch appears to be as effective in relieving menopausal symptoms as the oral estrogen tablets. Studies to date suggest that its effect on calcium absorption and blood lipids are almost identical to oral estrogen.
Estrogen Vaginal Cream
The use of estrogen vaginal cream is much more limited in its clinical applications. Estrogen cream is primarily applied to the vagina and urethral area to prevent atrophy and breakdown of the tissues caused by lack of natural estrogen. Though estrogen is absorbed from the vaginal mucosa into the bloodstream and can affect other parts of the body, the effects tend to be undependable. Occasionally, however, my patients complain of more generalized side effects from using the vaginal cream, such as breast tenderness or mild fluid retention. These side effects often occur early in the course of treatment. Because of the vaginal atrophy that exists when women first begin treatment, estrogen tends to be absorbed rapidly. This can cause the blood levels of estrogen to rise significantly. However, once the estrogen thickens the vaginal walls and changes the cellular pattern of the mucous membranes to a more youthful and healthier condition, estrogen absorption into the bloodstream slows down. (It may or may not restore lubrication; the use of a lubricant cream or gel may still be needed.) Not only will estrogen thicken the vaginal wall, making it less traumatized by sexual intercourse or foreplay, but it also reduces the incidence of bladder infections.
Another benefit of the vaginal cream is that, like the transdermal patch, it does not make an initial pass through the liver. As a result, the use of estrogen vaginal cream may not aggravate liver or gallbladder disease, hypertension or clotting tendencies, unless clotting factors are abnormal. However, women with pre-existing breast cancer or who are also positive for estrogen receptors may not be good candidates for estrogen vaginal creams. This is currently being debated and the controversy may be resolved by using small topical doses with low risk.
Premarin cream is one of the most commonly used vaginal creams, although other brands are available. Premarin cream comes with an applicator that allows for the use of two to four grams per day (as calibrated by the applicator). One half to one full applicator of Premarin cream will delivery 1.25 to 2.5 mg of estrogen to the vaginal tissues. Many women find, however, that they function quite well at smaller doses, often as little as oneeighth of an applicator.
Initially, you may want to use estrogen cream daily, at least for the first week or two. Be sure that the most sore or abraded areas come directly in contact with the cream, either through placement of the applicator or by applying the cream to sore and tender areas with your fingers. After healing has begun and sexual activity is more comfortable, many women reduce usage to two or three times per week. Use it as often as required to keep your vaginal tissues healthy and functional.
Vaginal cream has several drawbacks, none of which are serious. The creams tend to be messy and can leak into your underwear. Estrogen vaginal cream should not be used as a lubricant or applied prior to lovemaking. Some men are concerned about the adverse effects of absorbing estrogen through their penis if the cream is still in the woman's vagina during sexual activity. Estrogen cream can, however, be inserted following lovemaking, particularly just prior to retiring at night.
If you are concerned about using estrogen for protection against osteoporosis or cardiovascular disease, estrogen vaginal cream is inadequate to meet these goals. You will have to use additional estrogen, either by the transdermal or oral routes to keep your blood levels of estrogen consistently high enough to confer protection. In addition, a course of progesterone needs to be used, at least every three months, to "clean out" the uterus and allow the lining to shed. The addition of progesterone will help mature the lining of the uterus and thereby prevent the buildup of cells that can lead to hyperplasia or even cancer.
Rarely, androgen cream is also prescribed in very small dosages, usually in 1 or 2 percent concentration, to help prevent vaginal discomfort and soreness. It is also used to help restore sexual desire or libido, a fairly common problem in menopausal women. It has certainly been an issue for many of my patients because it affects their quality of life, as well as the pleasurable aspect of their intimate relationships. Like estrogen cream, androgen cream is applied daily for a week or two and then decreased to twice weekly applications. Care must be taken not to overdose, since masculinization side effects such as excessive hair growth or clitoral enlargement can occur.
Alternative Routes for Estrogen Administration
You may also hear of several other routes of estrogen delivery. These methods tend to be used rarely or are more readily available in other countries.
Intramuscular Injection. Intramuscular injection was used occasionally before the development of the transdermal patch, and may still be used for women who can neither take oral estrogen nor the transdermal patch. This method does have several disadvantages. The injection delivers large amounts of estrogen directly into the bloodstream, then diminishes to lower levels with time. Thus, there is not a continuous delivery of the hormone to the body that the transdermal patch now makes possible. Finally, injections are usually given at monthly intervals and require administration in a physician's office which are expensive in terms of time and money.
Subcutaneous Pellets. A subcutaneous pellet of estrogen therapy, used during the 1960s and 1970s, is not currently a method of treatment. The hormone was impregnated into a solid pellet which was then implanted by a small incision into the subcutaneous fat of the buttocks or abdomen. The pellets would dissolve slowly, releasing hormone into the fatty tissues. Research is now oriented toward trying to improve types of implants, as well as the more controlled release of the hormone into the system. Thus, it is possible that subcutaneous implants will be used once again for ERT.
Buccal Estrogen. A low-dose estrogen tablet has been developed that can be placed directly against the mucous membranes inside the mouth. The tablet dissolves rapidly and the estrogen that is released from the tablet is absorbed directly into the bloodstream. Estrogen released by this method is sufficient to relieve common symptoms such as hot flashes. It is still pending approval by the US Food and Drug Administration.
Estrogel. Estrogel is a form of estrogen replacement therapy used frequently in France. The estrogen is in a gel-base that is rubbed on the skin of the abdomen and absorbed into the body. The dose can be varied easily by changing the amount of gel used.
Progesterone Therapy
Before the 1980s, all progesterone therapy had to be administered by injection. Women who required progesterone treatments for specific medical problems had to go to the doctor's office for every treatment. The development of oral progesterones made this hormone more readily available. Initially, progesterone was combined with estrogen in birth control pills for younger women. Progesterone's important role in preventing endometrial cancer in postmenopausal women on ERT was discovered in the 1970s. It rapidly became part of the standard hormonal regimen for postmenopausal women who still had their uterus intact. The traditional form of treatment does not, however, use the same natural form of progesterone produced by the ovaries. Instead, a synthetic form called a progestin is used. It was not until recently that some physicians actually began to use natural progesterone for postmenopausal support. In this section, I will discuss both the synthetic and natural forms of progesterone.
Oral Progestins. Oral tablets of synthetic progesterone are the most widely prescribed form of progesterone. The progestins change the cells of the uterine lining from a pattern of rapid growth to a more mature form. The cells become secretory in nature, which prepares the uterus to nourish and maintain an early pregnancy during the active reproductive years. With the proper dose and ratio to estrogen, once a woman stops progesterone the uterine lining is sloughed off and a menstrual period or bleeding episodes occur. All of the accumulated proliferated cells, tissue and blood leave the body. No pile up of abnormal cells occurs and the uterine lining is left healthy and ready for the next month's estrogen therapy, therefore reducing the risk of uterine cancer.