Hormone replacement therapy

Hormone replacement therapy (or HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced ina woman's body. HRT is sometimes referred to as Estrogen replacement therapybecause the first hormones that were used in the 1960s as medication were estrogen compounds. HRT has two primary purposes: preventive treatment againstosteoporosis and heart disease; and relief of physical symptoms associated with menopause.

Menopause is defined as the last spontaneous menstruation after which no further spontaneous menses occurs in the following years. Women who have had their ovaries removed surgically are said to have undergone surgical menopause. The exact time of menopause differs from woman to woman. Some women begin menopause at around 40 and others as late as age 55. It is a gradual transition and can take as many as ten years for the process to be completed. The early phase of the transition is called perimenopause.

When a woman passes through menopause, the levels of the sex hormones drop. The sex hormones produced in the body are estrogen, progesterone, and testosterone. The average life expectancy for a woman now is 80 years. This means that a woman spends almost a third of her life in an estrogen-deficient state. This has far reaching consequences for the various organs and can result in amultitude of clinical symptoms.

The most frequent symptoms associated with menopause can be classified into the following categories: Hemorrhage and menstrual cycle disorders: Some womencomplain of abnormally low periods, or excessively heavy periods. There maybe pre- and post menstrual bleeding. The periods become irregular, some timestoo frequent or very infrequent and sometimes there are no periods at all. Vegetative symptoms: Hot flushes, excessive perspiration, reddening of the skin, sleep disorders, attacks of dizziness, very severe headaches, heart palpitations, cardiac complaints, blood pressure variations, and constipation are common complaints. Psychic symptoms: may include wide variations in moods, emotional instability leading to depression, irritability, impaired concentration, and exhaustion leading to sleep disorders. Somatotrophic symptoms includeatrophic inflammatory changes of the vulva, vagina, bladder, and urethra, atrophy of the skin and breasts, complaints of pain during sexual intercourse, urinary incontinence and painful urination. Metabolic changes may also take place such as a tendency to gain weight, osteoporosis, rise in blood lipids (fats), arteriosclerosis, rheumatic changes and a tendency to develop diabetes and gout.

Hormone (or estrogen) replacement therapy is intended to improve and/or maintain quality of life and increase life expectancy. The amount of estrogen medication prescribed is not enough to be a replacement as it is only a fractionof the amount of estrogen that the ovaries usually produce. Many regimens areavailable to the post-menopausal woman to choose from.

HRT regimens consist of the administration of estrogen, and, if indicated, progesterone (progestins) and/or testosterone. When progesterone is added to estrogen in the therapy program, it is called "hormone replacement therapy". Estrogen is the ovarian hormone that is responsible for the development and maintenance of a woman's secondary sexual characteristics. Progesterone is the ovarian hormone that is responsible for protecting the uterine lining from being overly stimulated by estrogen. Estrogen, if given alone may sometimes result in the development of abnormal changes of the endometrium (uterine lining)including cancer. Therefore, it is essential, when the uterus is present, that progesterone be administered in the HRT regimen. Adequate amounts of progesterone in a HRT program can safeguard the uterus from being overly stimulated and prevents abnormal changes of the lining of the uterus. A woman who hashad her uterus removed in a hysterectomy has no need to take! progestins. Testosterone is the sex hormone most closely associated with sex drive and is also a factor in energy levels and the preservation of muscle mass.

There is no method for HRT that can mimic nature precisely. During a woman'sreproductive years, the peaks and valleys of the hormone concentration in theblood are necessary to trigger ovulation, menstruation, conception and to maintain a pregnancy. These swings in the hormone levels affect a woman's moodsand sense of well being.

All of the sex hormones, estrogen, progesterone, and testosterone can be administered alone or in combination in the HRT program. There are a number of routes of administration. These include: Oral, Transdermal patch, Transdermal gel, Sublingual, Injections, Creams, and Subcutaneous implants. There is no "best method" for everybody and a woman's choice may be influenced by a varietyof factors such as the type of menopause, age at menopause, any existing medical conditions, symptoms, current age, response to previous therapy (if any)and so on. The choice of the hormone(s) and the route of administration should depend on the individual and what she is comfortable with.

In the "oral route" of HRT, a tablet is taken daily. The most well known oralestrogen replacement product is sold under the brand name "Premarin". As thename suggests, the product is extracted from a pregnant mare. The advantagesof the oral route are that it is easy to take as a pill, it is relatively inexpensive, and for most women it effectively delivers estrogen into the bloodstream. The disadvantages are that it is not effective for everyone. It maycause nausea and stomach upsets and headaches in some women. This is becausethe tablet is absorbed by the upper gastrointestinal tract and transported directly to the liver. This abnormally high amount of estrogen arriving at onetime induces the liver cells and alters the production of various enzymes. Inrare instances, it may cause an elevation in blood pressure. The "transdermal patch" which is a patch that is applied to the skin can be effective in patients who do not respond to tablets. These have to be replac! ed only once ortwice weekly as opposed to the daily tablets. The estrogen is gradually absorbed over the length of time the patch is worn and therefore is more physiologic. In 10 - 30% of women who try it, the patch may cause skin irritation. Itmay also not be a method of choice for women who live in warmer climates andwho exercise strenuously. The "transdermal gel" may be a useful method of HRT in such cases. A measured amount of gel is rubbed directly onto the skin once daily. It is absorbed by the skin and released gradually into the blood stream. However, it is not widely available in the United States.

In the "sublingual" mode of administration, a tablet usually "estradiol' is placed under the tongue. It is absorbed through the lining of the mouth into the blood vessels located under the tongue and then into the blood stream. Itthus avoids the "first liver pass". In the "intramuscular injection", the hormone is usually mixed with a substance that slows its release into the bloodstream. The patient is injected at 2-4 week intervals. "Creams" and "suppositories" have been used as a method for hormone replacement in order to counterthe vaginal dryness and loss of elasticity of the vaginal barrel that is often a distressing symptom of hormone deficiency. "Subcutaneous implantation" of estrogen pellets is a method used for women who have been unresponsive to other therapies. The pellets, which consist of estradiol, are inserted into the subcutaneous tissue of the abdomen or buttock usually at 3-6 month intervals.

HRT programs for women who are to be given both estrogen and progesterone canbe either cyclical therapy or combined therapy. In cyclic therapy, the progesterone is given for part of the month (10 - 12 days)in a tablet form while estrogen is administered daily. Estrogen stimulates and thickens the uterine lining and then the progesterone, which has the anti-estrogenic effect blocksthe estrogen stimulation. Progesterone both shrinks the uterine lining and prevents the development of abnormal changes. If the treatment works as it should, then, 2 - 5 days after finishing the progesterone, the patient experiences "scheduled withdrawal bleeding" which usually lasts from 3 -5 days. In addition, this cycle is repeated monthly. If the bleeding occurs at any other time of the month, it is called "unscheduled bleeding" and signals the need to determine if any overgrowth or abnormal change of the uterine lining is present.

In the combined therapy, estrogen and progesterone are taken daily. The benefit of this regimen is that in the majority of cases daily progesterone even in small doses keeps the uterine lining thin and no bleeding occurs.

Some women take the hormone treatment even if they are not suffering from anycomplaints of menopause. Their doctors believe that the hormone treatment compensates the estrogen deficiency occurring in menopause. Besides alleviatingthe complaints, HRT protects from osteoporosis (bone loss) and cardiovascular diseases. There is no specified treatment period for HRT. Typical menopausal complaints such as hot flashes, and sleep disorders occur only during a period of two to five years. If the treatment is primarily carried out to alleviate these symptoms, it can be terminated after that. However, in order to specifically counteract increased bone fragility, estrogens should be used for at least eight to ten years. Some experts even recommend life-long use of estrogens, since in many cases increased bone atrophy recurs after discontinuation of treatment.

Diminished hormone levels interfere with optimal sexual function by loweringsexual desire and causing some changes in the hormonally sensitive tissues. The mucous membranes of the external organs and in the vagina become thinner and more sensitive due to estrogen deficiency in menopause. The vaginal moisture also decreases. As a result, sexual intercourse becomes unpleasant and even painful. Although estrogen plays a part, the hormone most closely associated with sex-drive is testosterone. In women who have had their uteruses removed in a hysterectomy, if the surgery is performed before menopause and the ovaries are preserved, then the hormone secretion is unaffected. However, in a significant number of such patients, ovarian failure follows within three years of surgery. If this happens, a diminished libido and other menopausal symptoms would reflect the decline in hormone levels. If surgery is performed prior to menopause and the ovaries are removed, the fall in estro! gen and testosterone levels is abrupt and severe. This type of surgically induced menopausewould cause a dramatic fall in sexual desire. Many of the frequently prescribed regimens of HRT will maintain or restore libido.

HRT is recommended by many doctors for menopausal women because it could helpto prevent osteoporosis. Osteoporosis is a disorder in which bones become very brittle and can be easily fractured. In postmenopausal women, the lower levels of estrogen in the blood lead to a weakening of the bones. About 25% ofCaucasian women will develop severe osteoporosis. Asian women have a slightlylower risk; Latin and African American women are least at risk. In addition,menopause before age 40, kidney disease and dialysis, thin body build, thyroid medications, childlessness, lack of exercise, poor food choices, lack of vitamin D, high caffeine consumption, low calcium intake, smoking and alcoholabuse, cortisone therapy etc. are some of the other factors that put women ata higher risk of developing osteoporosis.

Hormone replacement therapy is given to lessen the short-term discomforts ofmenopause and decrease the long-term risks of decreased estrogen levels. Research has indicated that HRT has several potential benefits such as: * reliefof menopausal symptoms such as hot flashes, night sweats, vaginal dryness, decreased libido * prevention of bone loss * protection of heart health and a decrease in risk of strokes * improved memory and possible delayed onset or lowered rate of Alzheimer's disease * possible lowered risk of colon cancer * decreased rate of urinary tract infections * protection of dental health. * decreased rate of macular degeneration (leading to blindness)

The potential side effects of combined estrogen and progesterone replacementtherapy are formation of blood clots, premenstrual-like syndrome, headaches,fluctuating sugar levels, and edema (swelling due to water retention). Estrogen therapy, when given by itself may pose an increased risk of breast cancerand uterine cancer. The risk of developing uterine cancer is diminished verysignificantly, if progesterone is used in the treatment. Depending on the mode of administration, estrogen replacement therapy may sometimes cause gall bladder disease, irregular vaginal bleeding, stomach upset and higher blood pressure.

Hormone replacement therapy may not be recommended if the woman has the following problems: * if the woman is currently pregnant * has heart or circulation problems * family history of breast cancer or uterus cancer * history of stroke or blood clots * liver or gall bladder disease * suffers from any condition that may worsen by fluid retention such as seizures, headaches, heart, kidney and liver disease

When deciding whether to use HRT and which therapy to use, the following factors have to be discussed with the physician: the woman's age, medical history, reason for treatment, severity of menopausal symptoms, and possible side effects. In addition, the woman's family history of estrogen dependent cancerssuch as breast and uterus; risk for developing heart disease, risk for developing osteoporosis should also be taken into consideration.

When undergoing HRT, it is important be informed of any medical changes suchas abnormal vaginal bleeding. All the yearly physical examinations should beconducted such as pelvic exam, Pap smear, breast exam etc. The breast self-exam should be done every month. A yearly mammogram and a yearly endometrial biopsy (if estrogen is being taken alone) should be conducted. The blood pressure, sugar, cholesterol, and lipid levels should be checked periodically.

All HRT medications available used in the United States are available only with a doctor's prescription. There is still considerable disagreement in the medical community over the advantages and disadvantages of HRT. The most important controversy is whether it increases a woman's risk of developing breastcancer. Some studies have shown that the risk of breast cancer rises with thelength of time a woman has been taking HRT. An American study published in June 1998 concluded that the risk of developing breast cancer increases by 2.3% for each year the woman takes HRT. A Swedish study found that the risk of breast cancer doubled after six years of treatment, which agrees with the American findings that the risk is connected to the length of the treatment.

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