Friday, January 9, 2009

Menopause and Medical Drugs Treatment

Introduction

As women reach their late forties or early fifties, their menstrual periods generally become much less frequent and then stop. Sometimes called the "change of life" or the "climacteric," menopause is the time when menstrual periods end. Some women see menopause as a time for celebration while others dread the physical signs of aging. Most women treat it as a normal stage of life.

What is it?

Menopause simply means the end of menstruation. Usually defined as not having had a menstrual period for 12 months in a row, menopause may be natural or it may occur after a hysterectomy (surgical removal of the uterus). In the United States, the average age of natural menopause is 51 years, but it may occur naturally at any time between the ages of about 45 and 55 years.

Menopause results from decreased production of the female sex hormones, estrogen and progesterone. After menopause, few eggs remain in the ovaries. As a result, both estrogen and progesterone levels fall. The extreme decline in hormone production is a major cause of symptoms, such as hot flashes and mood disorders, which frequently accompany the start of menopause. Lowered estrogen and progesterone levels also contribute to an increased risk for certain health problems, such as heart disease, osteoporosis, and urinary incontinence (the inability to control urine flow). When levels of both hormones decline, menstruation stops and fertility essentially ends, as well.

Perimenopause is the time just before and after the onset of menopause. It averages 4 years in length, but it may be much shorter or longer for individual women. Because women may still release eggs during perimenopause, they can still get pregnant. Common symptoms that may begin in perimenopause include:

  • Changes in menstrual periods
  • Hot flashes
  • Insomnia
  • Mood changes
  • Night sweats

Postmenopause refers to the time after menopause. This is the time when some of the distress from the changes from menopause will start to fade. The symptoms described above may become milder, while energy levels and emotions stabilize.

What causes it?

Menopause is a natural part of the aging process for women. Each girl is born with a limited number of immature eggs in her ovaries. A complex balance of female hormones promotes the maturation and release of the eggs by the ovaries. With each menstrual period, some of the eggs are lost. As the number of eggs in the ovaries decreases, less estrogen is produced and menstrual periods usually become irregular before they stop completely. For most women, the process is gradual, but some women experience abrupt physical and emotional changes. For unknown reasons, some young women undergo menopause many years before expected. Women of any age enter menopause if the ovaries are removed surgically or if they are damaged (for example, by chemotherapy or radiation). In menopause caused by ovarian surgery or damage, the production of estrogen and progesterone drops suddenly.

Who has it?

All women will experience menopause. The average age is in the early fifties, but some women undergo menopausal changes much earlier or later in life. Emotional stress, certain illnesses, some medications, or excessive exercise can cause even very young women to stop menstruating temporarily. In rare cases, temporary cessation of the menstrual cycle may become permanent if the underlying cause is not corrected. Women who smoke cigarettes generally enter menopause a few years earlier than non-smokers.

What are the risk factors?

Risk factors are characteristics that make individuals more likely to develop a disease or condition. For menopause, the only risk factors are being female and approaching 50 years of age. However, younger women with certain risk factors can experience menopause earlier in life. For example, women who undergo surgical treatments such as hysterectomy (removal of the uterus), have genetic disorders that affect the ovaries, or who use certain types of cancer therapies may experience menopause at a younger age.

Menopause increases risk factors for other health conditions. When a woman stops producing female hormones naturally, she loses the protective effects of those hormones. For example, her rate of bone loss speeds up, making the development of osteoporosis causing broken bones more likely. Her risk of heart disease also increases, partly due to higher cholesterol levels that occur after the production of female hormones stops. Estrogen and progesterone were formerly prescribed widely to help prevent heart disease among postmenopausal women. However, the results of large studies have found they not only do not protect against heart disease, they may actually increase heart disease risk for some women. The American Heart Association (AHA) now recommends against the use of estrogen and progesterone if they are taken only to prevent heart disease. If hormones are taken to relieve the symptoms of menopause, some guidelines now suggest they be used no longer than needed - 5 years, at the most.

What are the symptoms?

Menopause is usually associated with distinctive symptoms. Although many women have very little trouble dealing with menopausal symptoms, about 40% of American women report symptoms that disrupt their normal functioning to some extent. Approximately 85% of women experience vasomotor symptoms - most often hot flashes. Vasomotor refers to the interactions of muscles and nerves that cause blood vessels to shrink and expand. Although the exact causes of vasomotor menopausal symptoms are not yet known, they are associated with disruption of the body's temperature regulation by changing hormone levels. Hot flashes are sudden, unprovoked feelings of heat, usually on the face, head, neck, and chest. They may be accompanied by rapid heartbeats, reddened skin, and/or heavy sweating. Typically beginning a year or more before menopause, individual hot flashes may last for a few seconds or for several minutes. They may occur singly or in groups. Only a few may occur per day or they may occur frequently. Hot flashes may happen at any time of the day or night, and they may persist for several years. Generally, both the length and the number of hot flashes decrease gradually until they eventually disappear for most women.

Other symptoms of menopause may include:

  • Decreased interest in sexual intercourse
  • Difficulty in concentrating
  • Dry, thin, easily bruised skin
  • Inability to control urine
  • Insomnia
  • Mood changes (such as anxiety, depression, and/or irritability)
  • Night sweats
  • Spotting (small amounts of blood from the vagina) and/or abnormal vaginal bleeding
  • Thinning or lost hair
  • Vaginal dryness
  • Urinary Tract Infections
  • Vaginal infections
  • Waking up earlier than usual
How is it treated?

For nearly 50 years, the standard treatment for menopausal symptoms was replacing one or both of the major female hormones, estrogen and progesterone. Hormone replacement therapy, often abbreviated as "HRT," restores both estrogen and progesterone. Since estrogen alone may increase the risk of uterine cancer, HRT is prescribed for menopausal women who have not had surgery to remove the uterus. Progesterone decreases the risk of endometrial cancer and so, is said to "oppose" the uterine cancer-promoting side effects of the estrogen. Progesterone also regulates fluid balance, restores libido, and helps to build bone. Replacement of estrogen alone (estrogen replacement therapy or ERT) is often used for women who have had a hysterectomy (surgical removal of the uterus) since they no longer are at risk for uterine cancer. Therapy aimed at decreasing symptoms of menopause is usually given only for a short period of time. If hormone replacement therapy is used for prevention of osteoporosis, the therapy must be taken for longer. Although still used today, it is now known that in addition to the benefits of this therapy, there are risks involved. Based on the results of several trials, both the risks and benefits of hormone replacement must be weighed to determine if it is the best option for an individual. For some women, symptoms of menopause can be managed by making lifestyle changes. Read the section on Helping Yourself.

Two large, long-term studies and several smaller ones concentrated on defining the risks and benefits associated with ERT and HRT. In 1998, results from the Heart and Estrogen-Progestin Replacement Study (HERS) found no heart disease prevention benefit from HRT. Those findings were confirmed in a follow-up study (HERS II) that concluded in 2002. The good news, however, is this study showed that after an initial treatment period of 2 years with hormones, the risk of blood clots declined to a non-significant difference. Therefore, long-term there seems to be no increased risk of blood clots. The HERS II study also demonstrated that there were no differences between the hormone group and the placebo (inactive pill) group in the incidence of any types of cancer.

An even larger study, the Women's Health Initiative (WHI) sponsored by the National Heart, Lung and Blood Institute of the U.S. National Institutes of Health also examined the use of both ERT and HRT by thousands of women. The part of WHI that concerned HRT began in 1993 and ended in 2002 before the planned end date. It was stopped when higher rates of breast cancer, heart disease, stroke, and blood clots in the lungs were found in women who were taking HRT than in women taking a placebo. The study did find a decrease in hip fractures and colon cancer for those women taking HRT.

The estrogen-only part of the WHI, scheduled to end in 2005, was also stopped early (in February 2004) after results showed that estrogen apparently increased the risk of both stroke and dementia (decreased mental functioning). Benefits from treatment in this study included a reduction in fractures, conferring protection from osteoporosis. Neither part of WHI found any benefit for ERT or HRT in preventing heart disease.

The Women's International Study of Long Duration Oestrogen After Menopause (WISDOM) was a study performed in the United Kingdom, Australia, and New Zealand. The study was designed similarly to the Women's Health Initiative study. The trial was stopped early following the publication of results from the Women's Health Initiative study. Reports of results from the portion of the WISDOM study that was completed were consistent with those from the Women's Health Initiative. Older women beginning HRT many years after the start of menopause were at greater risk for cardiovascular events and blood clots. The investigators suggested that research is needed to assess the long-term risks and benefits of starting HRT in younger women, who may have different effects than older women starting HRT.

To investigate this issue, a substudy of the estrogen-only part of the Women's Health Initiative was recently undertaken. The results of this substudy demonstrated that younger postmenopausal women who had had a hysterectomy and who took ERT had significantly less buildup of calcium plaque in their arteries compared to those who did not take hormone therapy. This is good news for younger women who have had a hysterectomy and want to use short-term estrogen therapy to relieve the symptoms of menopause. However, more studies in this age group are needed, and it should be noted that these findings do not alter the previous recommendation that hormone therapy should not be used to prevent heart disease.

For those taking HRT or ERT, the lowest dose that is effective should be taken. Taking HRT or ERT may not be a good decision for some women, however. Other types of treatment may be more appropriate for women who:

  • Have or have had breast cancer
  • Have mothers or sisters who have or have had breast cancer or ovarian cancer
  • Experience abnormal bleeding from the uterus
  • Receive active treatment for blood clots in the legs

Another option for women who are at risk for certain types of cancer or have failed treatment with prescription estrogens and progesterone is bioidentical hormones. The terms "natural" or "bioidentical" hormone therapy are used to describe hormone treatment with individually compounded recipes of certain hormones in various dosage forms. Based on the results of a person's salivary or blood hormone levels, the final composition of the compounded dosage form is individualized to that specific person. It is important to consider that saliva testing has not been proven accurate or reliable, and blood testing only provides hormone levels present in the blood at the time of testing. This may be a problem because blood hormone levels can vary throughout the day. Also, the desired levels of these hormones in the blood and saliva are unknown.

Proponents claim that natural hormone therapy is better tolerated than manufactured products. Most manufactured oral hormone products require metabolism by the body to be broken down into a form that the body can use. Metabolites are left behind that your body does not use and are the likely culprits of causing side effects. Bioidentical hormones are chemically identical to the hormones which your body produces and do not require metabolism. However, there is no approved preparation method for these compounded products, and methods will differ from one pharmacist or pharmacy to another. This can result in patients receiving inconsistent amounts of medication. Currently this treatment option is not recommended over FDA-approved prescription products.

Drug classes used to treat Menopause

  • Androgen and Estrogen Combinations
  • Estrogens
  • Estrogens - Vaginal
  • Progestins
  • Topical Estrogens

What is on the horizon?

The National Center for Complimentary and Alternative Medicine (NCCAM), a division of the U.S. National Institutes of Health, is currently conducting several clinical trials investigating the effectiveness and safety of natural menopause treatments. Black cohosh, soy and other isoflavones, and red clover are the primary agents being studied. However, clinical studies to date have failed to demonstrate positive results with these natural products.

Some evidence suggests that antidepressant drugs may help to control hot flashes. In small studies involving women with hot flashes, drugs known as selective-serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, and paroxetine, relieved hot flashes up to twice as well as placebo. Another type of antidepressant, venlafaxine, has also shown effectiveness. Possible side effects from antidepressants include constipation or diarrhea, dry mouth, insomnia, nausea, and sexual dysfunction. In addition, antidepressant drugs may interfere with the effectiveness of tamoxifen, a drug used to treat breast cancer.

Gabapentin, a drug used to control epileptic seizures and some types of pain, has also shown some promise for controlling hot flashes. A recent study has demonstrated that gabapentin appears to be as effective as estrogen in treating menopausal hot flashes. The exact mechanism of action in menopause is not completely understood, but it may help to normalize the body's temperature. In clinical and case studies of its use, women taking gabapentin reported reductions in other menopausal symptoms, such as mood changes and muscle aches, as well. Side effects, mainly dizziness, tiredness, and swelling in the hands or feet, were generally mild and appeared to be similar to those experienced by women taking estrogen only. Usually, side effects lessened after a few days of therapy. Gabapentin does not interfere with tamoxifen therapy for women who have breast cancer.

Also under study is the drug clonidine, which is commonly used to treat high blood pressure. Like gabapentin, clonidine can be used at the same time that tamoxifen is being taken. In case reports, clonidine relieved the length, number, and severity of hot flashes, at least mildly, for many women who were taking it. However the effects of clonidine on hot flashes wore off more quickly than anti-depressants or gabapentin. In addition to oral tablets, clonidine is available as a transdermal patch, which may be easier for some women to use. However, women taking clonidine experienced more problems with sleeping than women who were taking a placebo.