Hormone Therapy - Treating Menopausal Symptoms: Menopause Managing The Change Of Life
Content provided by the Faculty of the Harvard Medical School
Hormone therapy
Long the mainstay of treatment for menopause, hormone therapy remains the most effective treatment for hot flashes and vaginal discomfort. Some women report other benefits, such as improved joint motion and mental function. Your choices include different types of estrogens, progestogens, and androgens. Given the small but measurable increased health risks posed by hormone therapy, the current approach is to use the smallest possible dose for the shortest time possible. Your symptoms, your medical history, and your personal preferences will help determine which form to use. In addition to choosing the type of hormone, you and your clinician also need to choose a dose and delivery method. If you require both estrogen and progestogen, you will need to determine a regimen. With help from your clinician, you can tailor a treatment that's optimal for you. The following sections detail the various options.
Estrogens
Also referred to as "unopposed" estrogen, estrogen-alone therapy is recommended only for women who have had a hysterectomy because estrogen without progestogen greatly increases the risk of endometrial (uterine) cancer. Women who have an intact uterus but cannot tolerate the adverse effects of progestogen — bloating, moodiness and irritability, and sometimes spotty menstrual bleeding — may seek to take unopposed estrogen. But most clinicians will not prescribe it this way because of the increased risk of uterine cancer. Some women seek to avoid progestogen's side effects by not taking the progestogen in their hormone regimen while continuing to take the estrogen. This is a dangerous practice. Talk with your doctor about side effects and ways to minimize them. Any woman with an intact uterus who takes unopposed estrogen should have an annual endometrial biopsy to check for abnormal uterine cell growth.
Women who take hormone therapy can expect hot flashes to begin to subside within the first month of treatment. It can take up to three months to feel the maximum relief from hot flashes. You might have some side effects, including bleeding if you still have a uterus, nausea, breast tenderness, headache, mood swings, and changes in libido. Most women in the United States take estrogen in pill form, but it's also available in patches, gels, lotions, and even injections; there are also vaginal creams, rings, and tablets.
Progestogens
A progestogen is a hormone that acts like natural progesterone in the body. During the menstrual cycle, progesterone prepares the uterine lining for pregnancy by increasing its blood supply. If pregnancy doesn't occur, a drop in progesterone triggers shedding of the uterine lining. In the 1980s, progestogens were added to estrogen therapy because of their ability to slough off the uterine lining. This reduces the risk of endometrial cancer associated with estrogen alone. There are different types of progestogens, and the terms are sometimes used interchangeably, which can be confusing. The term progestogen includes both synthetic forms (called progestins) and natural forms (see Table 5).
Androgens
Estrogen isn't the only hormone that declines as women age. So do androgens. Androgens are steroid hormones, often regarded as male hormones, although they occur naturally in both men and women. The two main androgens, testosterone and DHEA, play a role in maintaining sexual desire, muscle mass, bone density, fat distribution, mood, energy, and feelings of well-being. Some clinicians think there are situations that may justify a trial of androgen supplements: removal of the ovaries, which causes an abrupt drop in estrogen and androgen production, or low sex drive that does not improve with estrogen. But the indications, risks, and benefits are uncertain at best, and there are no long-term data on the use of testosterone in women. The only FDA-approved testosterone product for women is a form of testosterone combined with estrogen and approved only for hot flashes.
Some experts have described an "androgen deficiency syndrome" marked by low androgen levels, low energy, and reduced sex drive. Even though laboratory testing can measure your androgen levels, the values are often not accurate because the tests are standardized to normal male values, which are far higher. There is little information to guide physicians in determining the appropriate blood levels of androgens for women at various stages in their lives. It's still not clear if and how women might benefit from androgen replacement therapy, but ongoing research may help clarify the situation.
| Choosing a health care provider
 Maybe your periods have become irregular, or you've just started to feel the heat of hot flashes. It's important to consult a health care provider who will listen to your concerns and work with you to determine the best options for symptom relief and disease prevention. Most primary care doctors can diagnose menopausal symptoms and help you find appropriate treatments. Still, some physicians are more knowledgeable about menopause than others. If your physician's recommendations don't relieve your symptoms and your doctor isn't able to answer all the questions you have about which treatments are right for you, it may be time for a specialist. Asking your doctor for a referral is probably the best place to start. A gynecologist or endocrinologist may be a good choice. Clinics that specialize in women's health are often oriented toward helping devise a strategy for treating symptoms specific to women and reducing their disease risks. Ask friends who have been to a specialist if they would recommend the doctor they've seen. The North American Menopause Society also has referral lists of its members in the United States and Canada at www.menopause.org. |
Combined hormone therapy
Combined hormone therapy usually refers to the combination of an estrogen and a progestogen, used to treat menopausal symptoms without increasing the risk of uterine cancer. You have several choices for combined hormone therapy. You can take the combination of an estrogen and a progestogen in a single pill (Prempro) or patch, or take estrogen and progestogen separately in pills, patch, a pill and a patch, or a pill and a gel (see Table 4), among other options.
Symptom relief from combined hormone therapy is much the same as it is for estrogen alone. Symptoms will improve in the first month, but the maximum effect may take up to three months. You may have intermittent bleeding for six months to a year after starting combined hormone therapy. Side effects from the progestogen include acne, bloating, weight gain, and mood swings. Not all women will respond the same way, so the doses or types of both hormones may have to be adjusted. Taking the estrogen and progestogen components separately enables you to tailor your doses to your specific needs.
Hormone regimens
Depending on your health history and personal preferences, you have several hormone regimens to choose from.
Low-dose oral contraceptives. Some doctors prescribe low-dose oral contraceptives to relieve menopausal symptoms and regulate periods while providing contraception during perimenopause. If you smoke or have high blood pressure, choose something other than birth control pills for these purposes, because they can increase your risk of heart attack and stroke. Some women prefer to skip the placebo pills in each monthly pack, taking hormones all month; this eliminates the period that normally occurs at the end of each month's pill cycle, and therefore lets them avoid symptoms such as migraines or hot flashes that can occur during the placebo week. One oral contraceptive, called Seasonale, is designed so that women take "active" pills (that is, those containing hormones) for three months straight before having a placebo week. This allows women to have a period just four times per year, which also minimizes perimenopausal symptoms.
Cyclic hormone therapy. This combination of estrogen and progestogen is often the best choice for women who are menstruating occasionally or have stopped recently. It mimics the body's natural premenopausal cycle and gives the endometrium an opportunity to slough off regularly so it does not build up and cause disturbing bleeding or become cancerous. The regimen involves taking estrogen every day and adding the progestogen for 12 or 14 days per month. Cyclic hormone therapy helps regulate periods and relieve symptoms during the erratic hormonal fluctuations of late perimenopause. However, it can have an additive effect that worsens symptoms at times when a woman's own estrogen level surges.
Continuous combined hormone therapy. This method of combined hormone therapy uses a constant dose of estrogen and progestogen taken every day. The daily progestogen dose is lower than that for cyclic hormone therapy. The goal is to eliminate periods completely. However, many women have some bleeding or spotting for the first six months to a year of using this method. This sporadic bleeding is one reason some women don't stay on continuous combined hormone therapy for long.
Constant estrogen, pulsed progestogen. This regimen, packaged in a single product, consists of only estrogen for three days followed by three days of combined estrogen and progestogen. You continue on in that pattern for as long as you take the medication. Protection from uterine cancer is about the same as with continuous combined hormone therapy, but this method offers greater benefits on cholesterol levels. Erratic vaginal bleeding still may occur while taking this product.
| Tapering off hormones Because current research suggests that it's best for women to take the lowest dose of hormones for the shortest possible time, many clinicians advise women to try weaning themselves off the drugs after a year or less, although many stay on the medications for several years or longer. A follow-up study of participants in the Women's Health Initiative who stopped their hormones abruptly found that among women who had symptoms before starting the study hormones, more than half said their symptoms returned after stopping hormones. On the bright side, many found that a range of strategies (mostly lifestyle changes such as drinking more fluids, exercising, and using fans or air conditioners) was helpful in relieving or coping with symptoms. There's little known about the best way to stop hormones, and there is no established regimen for doing so. Nor is there evidence that tapering can stave off the recurrence of symptoms. However, if you and your doctor agree that tapering off hormones is a good approach, try tapering during the winter rather than summer, when hot flashes tend to be worse. If possible, start during a low-stress time (not, for example, during or soon after any other major life transitions). If you take both estrogen and a progestogen separately, be sure to reduce the dose of both hormones. The specific strategy depends partly on the form you're taking. With pills, you can either skip a day or two or cut the pills in half. Skipping works better with certain pills than others because of how long the medicine stays in your system; your clinician can help determine this for you. Most patches can be trimmed with scissors. Stay on the lowered dose for five to six weeks (which is how long it takes your body to adjust), then drop down a little further. This slow tapering process can help you determine the lowest possible dose needed to relieve your symptoms, in the event that you end up needing to stay on the hormones a little longer. Vaginal symptoms tend to appear and disappear more slowly than hot flashes. Remember that you can use local estrogen, in the form of creams, tablets, or a ring, for vaginal symptoms. For more specific suggestions, consult your clinician. |
Patches, creams, rings
In addition to pills, there are a variety of other ways to take hormones. Patches, skin creams and gels, and one brand of vaginal ring (Femring) all contain hormones that work systemically to treat symptoms of menopause. With each of these, women with an intact uterus should use a progestogen in addition to the systemic estrogen. For women troubled mainly by vaginal dryness and who want to avoid the potential risks of systemic estrogen, there are estrogen products designed for vaginal effects only, including vaginal creams, vaginal tablets, and a ring (Estring).
Patches. Several brands of patches that deliver estrogen through the skin are available. Patches are worn discreetly on the abdomen or buttocks. Most of the patches marketed in the United States contain a form of estrogen called estradiol, in doses ranging from 0.025 mg to 0.1 mg. Estradiol enters the bloodstream rapidly, quickly reaching target tissues.
One type of patch is the reservoir patch, which has a waterproof backing and a small supply of the drug suspended in alcohol. The alcohol carries the drug through a membrane in the patch and into the skin. Another type is the matrix patch, which delivers estrogen through a layer of gel. This type of patch is thinner and less bulky than reservoir patches. Also, it can be cut with scissors if you want to reduce the amount of hormone delivered — a technique often used to taper off hormone doses.
Patches contain less estrogen than pills because the hormone isn't broken down by digestion. This reduces the risk of gallstones. Another potential benefit is that, unlike estrogen in pill form, patches and other transdermal products do not increase the levels of a protein called sex-hormone-binding globulin. This hormone binds with testosterone, which may result in a lower sex drive — a potential problem in women who take oral estrogens.
Combination patches are available containing both estrogen and progestogen, but if you want to adjust the doses, you will need to take the estrogen and progestogen separately. Women with sensitive skin may find patches cause irritation. If you notice any skin irritation, report it to your doctor. Usually each patch is effective for three to seven days. Patches are usually more expensive than pills, but a less expensive generic estrogen patch is available. Price may depend on your insurance carrier.
| If you use the patch
|
Transdermal gels and creams. One product, EstroGel, comes in a clear, odorless, alcohol-based gel that's delivered from a metered-dose pump. You apply the gel once a day on one arm from the wrist to the shoulder. The gel dries completely in two to five minutes. Another product, Estrasorb, is a cream that you rub into your thighs and buttocks; it comes in individual foil packets.
Vaginal rings. These products are inserted into the vagina, much like a contraceptive diaphragm. The ring releases estrogen gradually and needs replacement about every three months. One brand, Estring, produces only local effects, and is appropriate for women who want to treat only vaginal symptoms. A different brand, Femring, contains higher doses of estrogen and treats hot flashes in addition to vaginal dryness. Although the rings can be removed temporarily and reinserted, neither type has to be removed before sexual intercourse.
Vaginal creams. Vaginal creams treat only the local tissues of the vagina and typically do not treat systemic symptoms such as hot flashes. Because they are not systemic, vaginal creams do not carry the same benefits and risks as estrogen taken by pill or patch. Only small doses are needed to relieve vaginal dryness, a plus for women who want to relieve vaginal symptoms and avoid risks associated with higher doses of estrogen. If you have a uterus, you probably do not need to take a progestogen with a vaginal cream, but you may want to discuss this with your doctor. Even though these estrogen products are used in the vagina, they can enter the bloodstream if a large enough dose is used. Estrogen cream should not be used as a lubricant before intercourse; it's been known to be absorbed through a partner's skin.
Vaginal tablets. Estrogen tablets are inserted into the vagina with an applicator to relieve vaginal symptoms. Like the vaginal creams, this product can relieve dryness and irritation.
Who should avoid hormone therapy?
Because of the risks associated with hormone therapy, women with the following health conditions generally should not take hormones:
-
heart disease
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breast, ovarian, or endometrial (uterine) cancer
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stroke, deep-vein thrombosis, pulmonary embolism, or blood-clotting disorders
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liver disease
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unexplained vaginal bleeding
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known or suspected pregnancy.
The risk of hormone therapy for women with a family history of breast cancer or heart disease is unknown.
Table 4: Hormone regimens | ||
| Regimen | Days per month | Bleeding* |
| Continuous estrogen with cyclic progestogen | Estrogen every day; progestogen on days 1–12 or 1–14 | Regular, monthly bleeding in 85% or more of women, often lighter than a period |
| Continuous estrogen with continuous progestogen | Both estrogen and progestogen every day | Often irregular bleeding for the first 6–9 months (more erratic the closer a woman is to menopause) |
| Cyclic unopposed estrogen | Estrogen on days 1–25 | Unpredictable spotty bleeding for first 6–12 months |
| Continuous unopposed estrogen | Estrogen every day | Occasional spotty bleeding for 6–12 months |
| Continuous estrogen with long-cycle progestogen | Estrogen every day; progestogen on days 1–14 of every third month | Generally fairly heavy periods |
| Low-dose regimens | Can be administered in all of the above patterns | Generally less bleeding than with standard dose |
| *Postmenopausal bleeding outside these parameters is not uncommon, but may be a sign of uterine problems. | ||
Table 5: Estrogen products | |||
| Type of estrogen | Pills: For systemic relief of menopausal symptoms such as hot flashes and vaginal discomfort | Topical systemic products: For systemic relief of menopausal symptoms such as hot flashes and vaginal discomfort | Vaginal products: For local relief of vaginal dryness and discomfort |
| Conjugated equine estrogens (CEE) | Premarin |
| Premarin vaginal cream |
| Synthetic conjugated estrogens | Cenestin, Enjuvia |
|
|
| Esterified estrogens | Menest, Estratab |
|
|
| 17 beta-estradiol | Estrace, various generics | Alora, Climara, Esclim, Estraderm, Estrasorb, EstroGel, Vivelle, Vivelle-Dot* | Estrace vaginal cream, Estring vaginal ring |
| Estropipate | Ortho-Est, Ogen, various generics |
|
|
| Estradiol acetate |
| Femring vaginal ring | |
| Estradiol hemihydrate |
|
| Vagifem vaginal tablet |
| *All are skin patches except for EstroGel (a gel) and Estrasorb (a cream). | |||
Progestogen products | |||
| Type of progestogen | Pills: Taken with estrogen products to prevent endometrial cancer; also used to control irregular periods and for birth control | Vaginal gel: Taken with estrogen products to prevent endometrial cancer | IUD: Used to control irregular periods and for birth control |
| Medroxyprogesterone acetate (MPA) | Amen, Cycrin, Provera, various generics |
|
|
| Norethindrone (norethisterone) | Micronor, Nor-QD, Camila |
|
|
| Norethindrone acetate | Aygestin, various generics |
|
|
| Norgestrel | Ovrette |
|
|
| Micronized progesterone USP (in peanut oil capsule) | Prometrium |
|
|
| Progestogen |
| Prochieve 4% |
|
| Levonorgestrel |
|
| Mirena |
Combined estrogen/progestogen products | |||
| Type | Regimen: Combination products relieve symptoms while preventing endometrial cancer | Pills: For systemic relief of menopausal symptoms such as hot flashes and vaginal discomfort | Skin patches: For systemic relief of menopausal symptoms such as hot flashes and vaginal discomfort |
| CEE and MPA | Continuous-cyclic | Premphase |
|
| CEE and MPA | Continuous-combined | Prempro |
|
| Ethinyl estradiol and norethindrone acetate | Continuous-combined | Femhrt |
|
| 17 beta-estradiol and norethindrone acetate | Continuous-combined | Activella | CombiPatch |
| 17 beta-estradiol and norgestimate | Intermittent-combined | Prefest, Ortho-Prefest |
|
| Estradiol and levonorgestrel | Continuous-combined |
| Climara Pro |
Table 6: Coping with side effects of hormone therapy | |
| As with all medications, hormones may cause unwanted side effects. Here are some tips for minimizing some of the most common. | |
| Side effect | Coping strategy |
| Fluid retention, including swollen feet, ankles, hands, or abdomen | Cut back on salt, drink plenty of water, consider taking a mild diuretic (herbal or prescription). |
| Abdominal bloating or gas | Try lowering the dose of either hormone; switch to another estrogen/progestogen; try a skin patch instead of a pill. |
| Headaches | Cut down on salt, caffeine, and alcohol; drink plenty of water; lower estrogen, progestogen, or both; avoid MPA; switch to a continuous schedule or a patch to minimize hormone fluctuations. |
| Breast tenderness | Cut down on salt, caffeine, and chocolate; lower the estrogen and or progestogen dose or try a different one. |
| Mood changes | Cut down on salt, caffeine, and chocolate; drink plenty of water; switch to progestogen or try a different one; switch to a continuous regimen or a patch to avoid hormonal fluctuations; exercise regularly. |
| Nausea | Take pills with meals or in the evening before bedtime; switch to a lower estrogen or progestogen dose; try a different oral estrogen; switch to a patch. |
| Skin irritation under the patch | Keep skin under patch very clean; switch to a patch with a different adhesive; apply patch to a different area; switch to oral estrogen. |
| Other possible side effects include uterine bleeding, dizziness, and changes in the shape of the cornea, which make it difficult or impossible to wear contact lenses. | |
| Last updated: | August 13, 2007 |
|---|
Medical content reviewed by the Faculty of the Harvard Medical School. Harvard Health Publications, Copyright © 2007 by President and Fellows of Harvard College. All rights reserved. Used with permission of StayWell.
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