Hormone Replacement Therapy and The Menopause

Whether or not to use hormone replacement therapy (HRT) is a complex issue and should be discussed with your physician. The following is a list of topics covered in this discussion. Click to go to a specific entry.

Introduction

Hormones are chemicals produced by glands in the body that control many aspects of normal bodily function. In addition, scientists have made a variety of synthetic hormones. The major “female hormones” are estrogen and progesterone. These hormones are produced by the ovaries, and in small amounts by the adrenal glands (that are located on top of the kidneys). Small amounts of the male sex hormones called androgens are also produced by the ovaries and adrenal glands.

Significant amounts of estrogen and progesterone are produced in most women during the reproductive years. The gradual decline in estrogen production is something that all women eventually experience. This decline in female hormone production, or the perimenopause, usually begins around age 45 and ends by age 55, but may occur earlier or later. The menopause is technically your last menstrual period. On occasion, the ovaries may be surgically removed before natural menopause, resulting in a “surgical menopause.”

Even before the menopause, other conditions may cause a woman to produce inadequate amounts of estrogen.

Extreme weight loss from a nervous condition called anorexia nervosa may drop the total body fat content to a level that results in low estrogen production by the ovaries. Excessive exercise without adequate caloric intake may do the same thing and cause the monthly menses to stop. This is sometimes seen in dancers and gymnasts who are compulsive about their desire to be thin. These young women can themselves be at increased risk for bone fractures.

The decrease in female hormone production causes changes that vary from woman to woman. You may notice hot flashes (also called hot flushes) that wake you up in the middle of the night, vaginal dryness and irritation, and possibly even short-term memory loss. In addition to these symptoms, the decline in estrogen production increases a woman’s risk of heart disease and osteoporosis (brittle bones) with the possibility of fractures. To reduce the likelihood of these problems, many women choose hormone replacement therapy (HRT). As with any medication, there are potential side effects in addition to the benefits. This information will help you decide if you want to take HRT or not.

 

Your own Hormones

Estrogen production by the ovaries begins when a girl goes through puberty. A few of the many functions of estrogen include breast and female hair development, menstrual cycling, chemical support of pregnancy and reduction of osteoporosis and colon cancer. Estrogen is produced throughout the menstrual cycle, whereas progesterone is produced in significant amounts only during the last two weeks before menses begins.
Some women do not ovulate (release an egg) regularly and do not produce significant amounts of progesterone. This may allow a build-up of the tissue lining the uterus (called the endometrium) and in some cases increase the chance of developing precancer or cancer of the uterus. Progestin is a synthetic hormone chemically related to progesterone. Synthetic progestin and natural progesterone reduce the chance of development of uterine cancer as a result of estrogen stimulation.

What are the effects of low estrogen?

Hot Flashes – Help!

Hot flashes are the most frequent symptom of low estrogen. About 75% of women experience hot flashes with the menopause. A hot flash is a feeling of heat that spreads throughout a part or all of the body. 
Most women experience hot flashes from the chest level up, and many blush and/or sweat at the same time. Hot flashes occur most frequently at night and may last for several years but will eventually go away even if HRT is not given.

Change in mood is common

Sometimes women experience depression, nervousness, irritability, mood swings, and forgetfulness during the time before, during and after the menopause.  There is some evidence that HRT will improve these symptoms. But you should remember there are many other causes for these concerns other than estrogen deficiency. 
The most common of these “other causes” is stress, a condition very few women are immune to in our fast-paced world. Your physician should help determine which of your concerns are related to estrogen deficiency and which are not.

Vaginal issues

Vaginal dryness, along with irritation and itching,  is a common problem. These symptoms are sometimes confused with those of vaginal infection. Pain with intercourse is not uncommon. Similarly, pain or discomfort on urination as a result of inadequate estrogen may mimic a bladder infection. Of course, a woman who is estrogen deficient may also have vaginitis or a urinary tract infection.

Bone Degeneration

Osteoporosis is a degeneration of the bones that makes them weaker and more likely to break. The bones most commonly affected are those in the spine, arms, and upper legs. Both males and females begin to lose bone around age 40, but the bone loss is much greater in women after the menopause. The women most likely to suffer from osteoporosis include thin white and Asian women who go through early menopause without estrogen replacement, who have a low intake of calcium, do not get enough exercise, or who smoke.
Getting adequate calcium along with estrogen and weight bearing exercise (such as walking) will go a long way towards decreasing osteoporosis. You are encouraged to get 30 minutes of exercise 6 days a week and 1200 mg of elemental calcium per day either in your diet (three glasses of milk or the equivalent) or with supplements. Women with decreased bone density and those 65 and older should consume 1500 mg of calcium per day.

 

What About Alzheimer’s

A medical study (from Johns Hopkins and The National Institute on Aging, 1997) demonstrated a 54% reduction in the risk of developing Alzheimer’s Disease when taking HRT. More recently a study in The Journal of the American Medical Association (JAMA 2002) showed that prior use of HRT is associated with a reduced risk of Alzheimer’s disease in older women.
Another  study (part of the Women’s Health Initiative) demonstrated an increased risk of dementia and Alzheimer’s disease in older women taking estrogen plus progestin.  Many experts in the field feel this study was flawed due to the limited number of participants and the older age of the participants.

Eye and other concerns

Studies have shown that HRT may reduce the risk of age-related macular degeneration (the leading cause of blindness in the older population) and tooth loss. Further study is also needed to confirm these findings.

Should you take estrogen?

What are the benefits and the risks? 
As with any therapy, the benefits should clearly outweigh any potential risks. Hormone replacement therapy (HRT) is not risk free. The benefits are prevention or reduction of the effects of low estrogen. You and your doctor should decide what is best for you.

Benefits of HRT

Benefits of HRT may include:

  • reduction of hot flashes and night sweats
  • reduction of mood swings
  • reduction of osteoporosis
  • reduction of vaginal dryness and pain with sex
  • reduction of dry skin
  • reduction of heart disease

Risks of HRT

Risks of HRT may include:

  • heart disease
  • blood clot, stroke, and pulmonary embolus
  • breast cancer
  • uterine (endometrial) cancer
  • uterine fibroid enlargement
  • ovarian cancer
  • gall bladder disease
  • increase in impaired liver function

The Risks Associated with HRT should be considered before taking this medication(s).

A number of medical studies have raised concerns about risks of HRT, but the landmark study was the Women’s Health Initiative Study that began releasing data in July 2002. The first part of the study involved 16,608 women ages 50 to 79 years with an intact uterus (no hysterectomy). In women taking estrogen plus progestin (Prempro®), the study demonstrated an increased risk of invasive breast cancer, coronary heart disease, stroke, and pulmonary embolism (blood clots in the lungs). On the positive side, the study found a decrease in hip fractures and colon cancer in women taking this combination of hormones. More Recent data from the study (2004) showed no increase in the risk of heart attack and breast cancer on estrogen alone but did demonstrate an increased risk of stroke as see with the estrogen plus progestin.

Cardiovascular Disease

Cardiovascular disease, including heart attack and stroke, is the leading cause of death for women in the United States. In fact, ten times as many women die from heart disease as from breast cancer. The WHI Study showed increased risk of heart attack, stroke, and pulmonary embolus on combined HRT (estrogen plus progestin) but no increased risk of heart attack on estrogen alone. Because blood-clotting factors are not increased with transdermal estrogen (the patch) as happens with estrogen pills, it appears the transdermal estrogen may be safer. The American Heart Association issued a statement in 2001 in favor of using “statins” over HRT to reduce the risk of heart disease.
“Statins” are a group of drugs used to lower cholesterol. In addition to these considerations for prevention of cardiovascular disease, we must also consider smoking cessation, regular exercise, normal blood pressure, low cholesterol and possibly other dietary considerations, weight control and stress management.   Another risk factor that may be reduced from use of statins is elevated high-sensitive c-reactive protein.  Low-dose aspirin and limited amounts of alcohol may assist in reduction of heart disease.

Reduction of Heart Attack
On the positive side of HRT and cardiovascular disease, a 2007 medical study in Nature Medicine showed that estrogen helps block the attachment of cholesterol to the inside of blood vessels. But, HRT must be started near the time of natural or surgical menopause. A large Nurses’ Cohort Study showed a reduction in heart attack risk in women taking HRT.

Uterine Cancer

Estrogens have been reported to increase the risk of endometrial cancer (cancer of the lining of the uterus or womb). Women who have had a hysterectomy (removal of the uterus) do not have to worry about this. If you still have a uterus, taking a progestin or progesterone reduces this risk. In fact if you are taking both estrogen and progestin  or progesterone, your risk of uterine cancer seems to be less than if you are on no hormones at all.

Breast Cancer Scares Me!

Breast cancer is a concern to all women. It affects one in eight women. There are some medical studies showing a greater risk for death from breast cancer in women who take HRT than those who do not. Other studies have shown that women on HRT who develop breast cancer are more likely to have tumors that have not metastasized (spread) than women not on HRT – this can give a better prognosis (outcome). Part of the Women’s Health Initiative (WHI) study was stopped in July 2002 for those women who were taking (Prempro®) due to an increased risk of invasive breast cancer. The WHI Study reported in 2004 no increased risk of breast cancer in women taking estrogen alone. Regarding hormone replacement therapy in women who have had breast cancer, the American College of Obstetricians and Gynecologists states “there is no conclusive data to indicate increased risk of recurrent breast cancer in postmenopausal women taking HRT.” William Creasman, MD, a well-known ObGyn, states “the data to date suggests that HRT in the patient who has had breast cancer is not detrimental. In fact, some of the larger studies note significantly fewer recurrences and breast cancer deaths, and less mortality in HRT users, compared to matched controls.” If you have a strong family history of breast cancer, you may decide it is in your best interest not to take HRT. Whether or not you choose to take HRT, you should have regular mammograms and breast exams.

At a recent symposium sponsored by the San Antonio Cancer Institute, Dr. Hakan Olsson reported the findings of a large prospective cohort study on nearly 30,000 women aged 25-65 in Sweden. Hormone Replacement Therapy (HRT) that included progestin markedly increased the risk of breast cancer.

However, estrogen-only HRT did not significantly increase a woman’s breast cancer risk.

The overall cancer risk was not increased in all HRT users. The increased risk of breast cancer in women using estrogen plus progestin was balanced by a decreased risk of other tumor types, especially colon and smoking-related cancers. This suggests that the tumor sites are shifted but with no overall increased risk of cancer. Combined (estrogen plus progestin) continuous HRT use for 1 to 48 months increased the risk of breast cancer 1.37 times over women never taking HRT. When used more than 48 months, there was a 4.6-fold increased risk of breast cancer. If the progestin was taken sequentially (usually 10-14 days each month), the risk of breast cancer was 2.23 times increased over never-users. What do these numbers mean for the individual woman? A 50-year-old Swedish woman who never used HRT or used estrogen-only HRT has a 2% chance of developing breast cancer over the next 10 years. If this woman used a progestin-containing HRT on a daily basis for at least 4 years, she would have a 7% chance of developing breast cancer over the next 10 years. The author commented that a low-dose progestin-releasing IUD might be an option for the woman who has not had a hysterectomy and needs HRT. This, at least in theory, should reduce the risk of progestin-related disease. Other medications are being studied that may provide lower-risk alternatives to traditional HRT in the future. Tibolone is a synthetic steroid with beneficial effects on bone and menopausal symptoms but apparently without any affect on breast cancer. The drug is being used in Europe and is under review by the Food and Drug Administration in the United States.

Gall Bladder Disease

Women taking HRT may have a greater chance of developing gall bladder disease which could make it necessary to have the gall bladder surgically removed.

Other Problems

Estrogens may cause breast tenderness, fluid retention and swelling, mood changes, nausea, and pelvic cramping. Estrogens may cause fibroid tumors of the uterus (usually benign muscle tumors) to enlarge and to cause bleeding. Estrogens should be used with caution in women who have impaired liver function. Although we do not large studies regarding, liver disease and HRT, transdermal estrogen may be safer because it does not make a first-pass through the liver like oral estrogen does.

Oral estrogens increase the risk of thrombophlebitis, blood clots that usually occur in the leg. A very dangerous form of thromboembolic disease is pulmonary embolus in which the clot breaks off from the vein and travels to the lungs. The frequency of pulmonary embolus was shown to be increased with estrogen plus progestin. Recent data shows that transdermal estrogen (“the patch”) does not increase the risk of thrombophlebitis.
Oral estrogen increases blood-clotting factors when it is absorbed through the gastrointestinal tract and makes a first pass though the liver. Transdermal estrogen goes directly into the blood stream and does not make this first pass through the liver. This also applies to estrogen shots.

Ovarian Cancer

A  medical study demonstrated an increased risk of ovarian cancer when taking estrogen without progestin in women who still have one or both of their ovaries (Lacey JV, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA. 2002; 288:334-341). A total of 44,241 postmenopausal women who participated in the Breast Cancer Detection Demonstration Project were evaluated in this study. Included in the study were both women who had had a hysterectomy and those who had not. The women in the present study had one or both ovaries present. Three hundred and twenty-nine (329) women were identified with ovarian cancer. This study showed an increased risk of ovarian cancer in women who have one or both ovaries (with or without the uterus present) and who take estrogen alone. Women who take estrogen plus progestin in this situation were not found to be at increased risk for ovarian cancer.
 There was also an increased risk of ovarian cancer with longer use of estrogen-alone HRT (7% per year). The overall increased relative risk was 1.6 times that of women not taking HRT. For women taking estrogen alone for 10-19 years the relative risk was 1.8, and for those taking estrogen alone for 20 or more years the relative risk was 3.2. Unlike the Women’s Health Initiative study that was a prospective double-blinded study (the most scientifically valid type of study), this study showing a relationship to estrogen therapy and ovarian cancer was an observational study. This type of study cannot prove cause and effect, but the results are worrisome enough so patients and physicians should carefully consider whether or not to take estrogen alone if one or both ovaries are present. This information further supports the need for an individualized approach to management of the menopause between the patient and her physician.

Alzheimer’s

The relationship between HRT and Alzheimer’s disease and dementia is still under investigation. As noted under Benefits of HRT (see above), a recent study showed an increased risk of Alzheimer’s and dementia in older women taking combination estrogen plus progestin. It is not yet known whether estrogen alone or estrogen plus progesterone have similar effects, or whether they may be beneficial. Some data suggests that women started on HRT around the age of the menopause may have improved brain function and those women started on HRT at an older age may have a decline in brain function.

Contraindications to Hormone Replacement Therapy

Many women may benefit from hormone replacement therapy, but not every woman can take it safely. If any of the following apply to you, HRT should be avoided.

  • Known or suspected cardiovascular disease (CVD) – it is not yet known what effect estrogen alone, especially using the transdermal route (thepatch) will have on existing CVD.
  • Known or suspected pregnancy.
  • Known or suspected breast cancer except in appropriately selected patients.
  • Known or suspected estrogen-dependent cancers such as cancer of the uterus.
  • Abnormal uterine bleeding that a cause has not yet been identified.
  • Active thrombophlebitis or thromboembolic disease (inflammation with or without blood clots in the veins or lungs) – if you have a history of previous thrombophlebitis or thromboembolic disease, therapy must be individualized by your physician.

Hormone Replacement Therapy

Hormone replacement therapy involves taking estrogen and progestin/progesterone if you still have your uterus (have not had a hysterectomy). As noted above, progestin/progesterone helps protect you from uterine cancer and may reduce the chance of ovarian cancer when one or both ovaries are present. If you have had a hysterectomy (with removal of uterus, tubes, and ovaries), you may take estrogen alone and in most cases may not need to take a progestin. As a result of the WHI study, the general recommendation is to limit HRT to less than 5 years (because of the increased risk of invasive breast cancer with time). 

If you stop HRT, your body returns to a “menopausal” state.

Whether you have had a hysterectomy or not, some women also take small amounts of male hormone, called androgens. An FDA Panel denied a request for approval of an androgen patch for treatment of sexual function problems. It acknowledged the patch showed some benefit but was concerned about long-term effects such as cardiovascular and breast cancer risk. Some women say they feel better when taking a small amount of androgen, but caution is appropriate.

Options for HRT

Hormone replacement therapy is still most commonly given in the form of pills. Other options include patches, injections, implants or pellets and suppositories and vaginal creams. HRT may be taken continuously or cyclically (cyclically means you do not take the HRT for a period of time, usually 5-7 days each month). 
If you have had a hysterectomy, there is no known benefit to cyclic therapy. Most women who have not had a hysterectomy and who take HRT cyclically will have a period. At some point in time, the endometrium (lining of the uterus) may not respond to the HRT, and bleeding will stop. The following are commonly used options for HRT.
  • Estrogen is still most commonly taken in the form of a pill, either on a continuous or cyclic basis. If continuous therapy is chosen, you will take one pill every day. Estrogen pills increase the risk of blood clots.
  • Transdermal estrogen (the patch) may be a safer route of administration due to reduced chance of thrombophlebitis (blood clots). The patch is usually applied once or twice a week.

minivelle

  • Estrogen rings may be a good choice for some women. These devices are flexible synthetic rings that are inserted into the vagina by the patient and release estrogen continuously. Potential advantages include insertion every three months rather than daily ingestion of medication or application of a patch once or twice a week. Also, the estrogen levels in the tissues are more constant. There are two different rings available. Estring® delivers a low dose of estrogen and is appropriate for treating vaginal dryness and other symptoms of estrogen deficiency localized to the pelvis (female organs). Femring® delivers a higher dosage of estrogen and can treat systemic estrogen deficiency. It can treat hot flashes and night sweats and reduce the risk of osteoporosis. Until proven otherwise, we have to assume Femring® has the same risks as other forms of estrogen. If you have not had a hysterectomy, a progestin or progesterone must be used along with the ring to reduce the risk of cancer of the uterus. There appears to be no increase risk of blood clots.
  • Vaginal estrogen suppositories or cream – depending on the specific product chosen, the effect may be systemic (absorbed into your body) or more localized in the vagina and pelvis. There appears to be no increased risk of blood clots.
  • Estrogen injections are usually taken every 3-4 weeks and appear to cause no increased risk of blood clots.

A progestin or progesterone should also be taken with the estrogen if you have not had a hysterectomy. A recent medical study suggests that women who still have one or both ovaries should take progestin with estrogen or not take hormones at all (see ovarian cancer above). The WHI Study demonstrated a number of risks as a result of taking estrogen plus progestin continuously. The most common schedules for administration of progestin or progesterone include:

  • one pill every day – after the first several months on this schedule, you should not have any bleeding.
  • one pill a day, 12 days each month
  • one pill a day for 14 days every three months
  • Progestin may also be given with the progestin IUD or with a patch that has both estrogen and progestin.

Designer Hormones, also called Bio-identical and Compounded Hormones

What about the so-called designer hormones that have been publicized in the non-medical press? This system promotes measuring a number of hormones in the blood, saliva, or urine. These include estrogen, progesterone, testosterone, growth hormone, and DHEA. A customized formulation of hormones is put together by a compounding pharmacist, based on the results of these hormone tests. 
The hormones used in the formulation are bio-identical to those found in the body. The “natural approach” of this system appeals to many women, although there is no evidence this is better or safer than the traditional approach to hormone replacement therapy. In fact, the American College of Obstetricians and Gynecologists (ACOG) discourages the use of these products due to the limitations in quality control.

HRT  Alternatives

Are there any alternatives to HRT if I cannot, or do not want to, take hormones? The answer depends on what desired effect of the therapy is. For instance, do you want to treat or prevent osteoporosis, reduce hot flashes or night sweats, or limit vaginal dryness and pain?

Please go to the section on osteoporosis if you are most interested in reducing bone degeneration. I cannot over-emphasize how important it is to discuss your options with your physician

Some women choose botanical (plant) medicines to supplement or replace prescription medicine when treating the menopause.

 

Soy products contain phytoestrogens (plant estrogens) which have weak estrogen activity. Soy products contain isoflavones that are structurally similar to estrogen. Some patients report that soy helps relieve estrogen deficiency symptoms such as hot flashes. Soy products do not seem to increase the risk of blood clotting like oral estrogen does. The standard amount of soy protein recommended is 40 grams per day (contains 118 mg of isoflavones).

Many other botanicals have been used for treatment of menopausal symptoms. Some of these include:

  • Black cohosh – thought to have estrogen-like effects but recently shown to couple to and block estrogen receptors – may cause stomach upset
  • Dong quai – a type of angelica – a recent medical study showed it has no more estrogen-like effect than a placebo (a medicine with no active ingredients that works by the power-of-suggestion) – may cause toxicity due to blood-thinning properties
  • Evening primrose – contains gamma linolenic acid which has been shown in one study to reduce night-time hot flashes of the menopause
  • Ginkgo biloba – improve concentration and memory by increasing blood flow to the brain
  • Ginseng – indicated for fatigue, lack of stamina, and inability to concentrate
  • St John’s Wort – mild anti-depressant, sedative, and anti-anxiety agent – similar action to prescription anti-depressants
  • Valerian root – has been shown to be mildly effective for treating nervousness and insomnia with no side effects
  • Wild yam extract – contain saponins which are similar in structure to progesterone but have no demonstrable progesterone activity in humans – some women report relief of some menopausal symptoms

Vitamin supplements help some women with menopausal symptoms but should not be viewed as a replacement for a healthy diet. In addition to a good multivitamin, vitamin B6 200 mg and vitamin E 400 units daily are sometimes helpful with premenstrual-like symptoms (moodiness, irritability, fluid retention, and breast tenderness). Other vitamin and mineral supplementation may be beneficial.

Summary

  • Do not take HRT to prevent cardiovascular disease, although there is evidence HRT begun at the menopause may reduce cardiovascular disease.
  • Use as low of a dosage as possible to get the desired effects.
  • Consider limiting treatment to 5 years or less.  As more information is gained regarding risks and benefits, this recommendation appears to be changing.
  • Transdermal HRT (“the patch”)  reduces the risk of thrombophlebitis (blood clotting problems). It appears that all forms of estrogen therapy other than the pill reduce blood clot risk when compared to the pill.
  • If progesterone/progestin is needed, natural progesterone appears to be safer than synthetic progestins.
  • Consider transvaginal estrogen to treat local pelvic problems such as vaginal dryness.

The approach to the menopause and hormone replacement therapy (HRT) has changed dramatically since 1999. Although concerns have been raised by the Women’s Health Initiative, long-term benefits and risks associated with HRT are still under evaluation. It is important to individualize therapy based on personal and family history. Choice of therapy should be an individualized one discussed with your physician.

The information provided by Advanced Healthcare for Women and E. Daniel Biggerstaff, III, M.D. is for informational purposes only. As each woman is unique, do not rely on this information for diagnosis and treatment. We cannot guarantee the accuracy of the content and advise that you see a qualified Health Care Professional for individual needs and care.

 Advanced Healthcare for Women
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Telephone 912-355-7717
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