Therapy with estrogen for menopause-related conditions is usually called estrogen replacement therapy (ERT). However, the term "replacement" is a misnomer because ERT provides only a small fraction of the estrogen once produced by the ovaries; estrogen supplementation is more accurate. The new term is estrogen therapy (ET).ET has been widely studied and used for more than 50 years by millions of women. ET is unique because it has the potential to help with a wide range of short-term disturbances, such as hot flashes and vaginal dryness. It also has the potential to prevent major diseases, such as osteoporosis and, possibly, heart disease. Some women report that they simply "feel good" while on therapy. Thus, if a woman needs therapy for many conditions, ET can be viewed as relatively economical "one stop shopping." If fewer conditions need treatment or if ET is not an option, more targeted therapies must be used, usually one therapy for each condition. There are many approaches other than ET for treating acute disturbances and preventing major diseases related to menopause.
Estrogen benefits women at particular risk for osteoporosis. Its role in prevention of heart disease, Alzheimer's disease, and other conditions later in life is still unclear. Women who have no identifiable risk factors for these diseases may still benefit from estrogen use for treatment of short-term conditions. Research is currently underway to determine which women will benefit most from estrogen therapy, at what dosage, and at what time of life. No ET is approved for use before menopause, although many clinicians offer ET for relief of symptoms during this transition time, and it frequently works.

Several dosage forms of ET are available, allowing a woman who needs estrogen to use exactly what is best for her:
• Systemic. When administered as an oral tablet, skin patch, intravenous injection, or in a custom made product such as a pellet implanted under the skin, estrogen circulates throughout the body's system (hence the term "systemic"), affecting many different tissues. All of these forms have the potential to reduce or completely stop the short-term disturbances of menopause and help in preventing osteoporosis and, possibly, heart disease. Although available, estrogen injections are not recommended for menopause therapy, since the estrogen level in the blood tends to peak too high after an injection and goes too low between injections, causing adverse effects.
• Local. When administered as a vaginal cream, vaginal ring, or vaginal tablet, estrogen is considered "local" therapy (one that affects only a specific or localized area of the body). Local dosage forms of ET are available to treat vaginal dryness and more severe vaginal atrophy and are, therefore, sometimes called "vaginal" forms. With a local form, only a very small amount of estrogen circulates through the body. Therefore, vaginal ET rarely helps with hot flashes or the prevention.
• Custom-made formulations are prepared by a compounding pharmacist from a prescription.
They allow even more specific tailoring of therapy, depending on what's best for a particular woman. Often-prescribed custom estrogen products are estriol cream and Tri-Est (a mixture of three estrogens: 80% estriol, 10% estrone, and 10% 17-beta-estradiol). Most women do not need customized formulations. Although much may be known about the active estrogen ingredient(s), little or nothing is known about the custom formulation that delivers the estrogen into the body. These products have not been tested in proper scientific studies as to purity, reliability, effectiveness, safety, and optimal dose. Since custom products are experimental, they must be used with caution.
The availability of estrogen in a variety of dosage forms, types, and strengths gives each woman a better chance to find what is best for her.
Finding the right regimen may require time, patience, and trying various prescriptions and delivery systems.

Some women have risk factors that are contraindications to ET use. Contraindications are reasons not to use treatment. However, the potential benefits sometimes outweigh the potential risks, leading a few women to accept therapy after careful consideration. In general, women who have the following should not use ET:
• Known or suspected pregnancy;
• History of breast cancer;
• History of hormone sensitive cancer;
• Unexplained uterine bleeding;
• History of blood clotting disorders.
(Cigarette smoking is not a contraindication for ET, as it is with oral contraceptive use in older women, but smokers are urged to stop before treatment starts for general health reasons.)
Side effects of ET. Potential side effects of ET are listed below. Many of these side effects can be managed using a variety of techniques (see Dealing with ET/HT Side Effects, later).
• Uterine bleeding (starting or returning);
• Breast tenderness (sometimes enlargement);
• Nausea;
• Abdominal bloating;
• Fluid retention in extremities;
• Changes in the shape of the cornea of the eye (sometimes leading to contact lens intolerance);
• Headache (sometimes migraine);
• Dizziness;
• Increased breast density (making mammograms more difficult to interpret).
Estrogen does not cause weight gain. However, in some women, ET can cause fluid retention in the hands and feet and/or abdominal bloating with gaseous bowel distension, sometimes resulting in a temporary weight gain. Increasing fluid intake, limiting salt consumption and participating in regular exercise will help reduce water retention.
There is one "side effect" issue that is important to keep in mind when ET is to be discontinued - stopping all at once typically brings on hot flashes. Tapering the dose over time is advised.

Estrogen probably does not cause cancer, but it may cause estrogen sensitive cancer cells to grow. It is well documented that using estrogen for five or more years can triple the risk of developing cancer of the endometrium. However, it is also well known that adding another prescription hormone - progestogen - to estrogen therapy reduces that risk to, or possibly even below, the level of taking no hormones. Combined estrogen and progestogen therapy is known as hormone therapy or HT.
Many women reject estrogen because they fear it may increase their risk of breast cancer. The relationship between hormones and breast cancer is currently a controversial issue. There is no evidence that the dosage known to relieve hot flashes and other acute changes during perimenopause increases the risk of breast cancer in the short term. However, the risk increases by as much as 40% when estrogen is used for long periods of time (defined by some studies as five years or more).
Thus, there is concern regarding ET/HT use for many years to help prevent diseases, such as osteoporosis which may not strike for 15 or more years after menopause.
Some scientists point out that the risk of breast or uterine cancer with ET/HT use is small compared with the benefits, which include the possibility of reducing the risk of heart disease. Heart disease is the leading cause of death for women. In fact, the risk of death from heart disease is many times higher than from breast cancer. In the United States, for example, a female at birth has a 23% lifetime risk of dying from heart disease compared with a 4% risk of breast cancer and 2.5% risk of bone fractures from osteoporosis. Further research will hopefully clarify some of the current uncertainties.
Weighing benefits and risks of ET. Studies have conclusively documented that estrogen taken for many years helps prevent osteoporosis and may also decrease the risk of heart disease. However, estrogen's protection against these diseases depends on its long-term, continuous use, which may slightly increase a woman's risk of breast cancer. Each woman must decide for herself if these potential rewards outweigh the potential risk. Only after examining and understanding her own situation and after a thorough consultation with her healthcare provider can a woman make the best treatment choice.
An informed decision does not rely on impersonal statistics or someone else's choice. It relies on the individual's current health status, her risk of developing more serious disease associated with prolonged low levels of estrogen, and the possibility that potential benefits of treatment outweigh the risks for her. If estrogen is not an option, there are many other effective options. A woman's decision about hormone therapy may also change as more
is learned through clinical trials and/or as personal situations and risk factors change.

Treatment that combines ERT plus a progestogen is called hormone replacement therapy or HT. When a woman with a uterus chooses to use ET,
the progesterone that the ovaries once produced  must be replaced to help counteract the increased risk of uterine cancer from taking ET alone. Replacement therapy is available as progesterone or as progestin (synthetic progesterone). Both forms are called progestogens. Women who have had their uterus removed (hysterectomy) are not at risk for uterine cancer and, thus, have no reason to take progestogen with ET.
Estrogen was prescribed alone (without a progestogen) in the United States until the early 1970s, when the associated increase in uterine cancer was recognized. Researchers found that combining a progestogen with ET kept the endometrium from thickening, which essentially eliminated the risk of uterine cancer from ET use. FDA-approved progestins (synthetic progestogens) were used initially because they were the only kind of progestogen that could be taken orally. More recently, micronized progesterone has become available in an FDA-approved oral formulation. Today, there are several progestogen options to allow tailoring to a woman's unique needs.

In most women, using a progestogen causes the lining to shed and pass from the uterus as bleeding, similar to a menstrual cycle, although there is no fertility. Some women find this unacceptable. For many women, it is difficult to decide whether to tolerate the bleeding in exchange for estrogen’s benefits, including relief from hot flashes and prevention of future diseases, such as osteoporosis.
Newer dosage schedules that combine estrogen and progestogen daily can eventually result in no bleeding in some women while still protecting the lining of the uterus from becoming cancerous. However, many women, particularly those recently menopausal, do have vaginal spotting and bleeding during the first six months of the regimen. Each woman will develop her own typical bleeding pattern when taking HT. Any change from that pattern should be reported to her clinician right away.
There are various HT schedules that can be used. Each woman should feel comfortable exploring different options with her clinician to determine which is best for her. These schedules include the following:
• Cyclic HT provides estrogen for 25 days each month, adding progestogen on the last 10 to 14 days, followed by three to six days of no therapy. Thus, both hormones are "cycled." The popularity of this regimen has waned because of uterine bleeding each month when the progestogen cycle ends and the possibility of hot flashes returning during the therapy-free interval.
• Continuous-cyclic HT (sometimes called sequential HT) provides estrogen every day, with progestogen added for 10 to 14 days each month. With this regimen, uterine bleeding occurs in about 80% of women when the progestogen cycle ends each month.
• Continuous-combined HT provides both hormones every day. The daily dose of progestogen used is much lower than the daily doses used in cyclic therapy, resulting in a lower cumulative dose over a month's time. Progestogen can stimulate bleeding, but since it is taken every day, the timing of uterine bleeding is unpredictable. With this regimen, bleeding occurs in about 50% of women, perhaps more in recently postmenopausal women. After several months of therapy, uterine bleeding often stops. However, the uterus is still protected from estrogen's effect on cancer risk. US women have been choosing this regimen more and more.
• Intermittent-combined HT is a new regimen (available as Ortho-Prefest) that provides estrogen every day, then adds progestogen intermittently in cycles of three days on, three days off. The cumulative monthly dose of progestogen is half that of a daily, continuous pattern. Bleeding and endometrial protection are similar to that with a continuous combined regimen. Some studies suggest that this regimen is better at preserving the beneficial effects of estrogen on cholesterol, thus helping heart health.
Dosage forms of progestogen and HT.
Progestogen is available in different forms - either alone or in combination with estrogen - allowing for individualized therapy. Not all progestogens are good choices for endometrial protection, but they can be used for other indications.
Progestogens are also available in custom-made formulations prepared by a compounding pharmacist following a healthcare provider's prescription
Hormone Replacement Therapy (HT) Is Not A Contraceptive.
Estrogens and progestogens are used in HRT to treat menopause-related changes; these hormones are also in most birth control pills. However, the doses of estrogen and progestogen used as HT are not high enough to provide birth control (except FemHRT). The doses used in birth control pills are about four or five times higher. Until menopause is reached (12 straight months without periods), hormonal or nonhormonal contraception must be used to avoid an unwanted pregnancy.
Progesterone creams that can be purchased over-the-counter may or may not contain progesterone. Even if they do, the amount of progesterone absorbed through the skin may not be sufficient to protect the uterus against cancer if estrogen is used.

In addition to uterine bleeding, the following side effects, some of which are similar to those of the premenstrual syndrome (PMS), may be experienced with progestogen use:
• Fluid retention
• Headache;
• Breast tenderness;
• Alterations in mood.
In some women, these side effects may be substantially reduced with the use of a bioidentical (natural) progesterone instead of a synthetic progestin. In addition, unlike progestin, progesterone does not appear to lower HDL, the good cholesterol that increases when estrogen is taken alone. More research is needed to clarify the effects of these hormones on heart disease risk.
Using progestogen is a complicated issue that depends, in part, on the type and dose of estrogen being used. The contraindications for treatment with progestogen are generally the same as those for estrogen.

There are various strategies to deal with the side effects that may occur with the use of ET or HT. Many side effects are temporary until a woman adjusts to the hormonal changes. Unless side effects are severe, a trial of three months of hormonal therapy is advised to see if side effects resolve. One strategy is appropriate for any side effect: stop ET/HT (by tapering slowly) to see if hormones are the cause, because side effects could be the result of something else.

• Fluid retention.- Restrict salt intake, maintain adequate water intake, exercise, try a mild diuretic.
• Bloating. -Lower the estrogen dose, switch to another estrogen, switch from oral estrogen to a skin patch, lower the progestogen dose, switch to progesterone or another progestin.
• Breast tenderness. -Restrict salt intake, cut down on caffeine and chocolate, lower the estrogen dose, switch to another estrogen, switch from oral estrogen to a skin patch, switch to progesterone or another progestin.
• Headaches. -Restrict salt, caffeine, and alcohol intake, ensure adequate water intake, lower the dose of estrogen and/or progestogen, switch to a continuous dosage schedule or a skin patch to avoid hormone fluctuations.
• Mood changes. -Restrict salt, caffeine, and alcohol intake, ensure adequate water intake, lower the progestogen dose, switch to progesterone, switch to a continuous dosage schedule or to a skin patch to avoid hormone fluctuations, exercise regularly.
• Nausea. -Take oral estrogen tablets with meals, lower the estrogen and/or progestogen dose, switch to another estrogen, switch from oral estrogen to a skin patch.
• Skin irritation under patch. -Switch to a patch with a different adhesive, apply patch to a different area, change to oral estrogen.

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