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Philippine Society of Climacteric Medicine

POGS Building, 56 Malakas St., Diliman, Quezon City Telefax No.: 433-9776 P.O. Box 1252, Quezon City, P.O. 1152, Quezon City

The Officers and Board Members

President

Corazon T. Lim, M.D.

Vice President

Santiago A. del Rosario, M.D.

Secretary

Evelyn Palaypayon, M.D.

Treasurer

Eileen M. Manalo, M.D.

P.R.O.

Lyra Ruth Clemente-Chua, M.D.

Auditor

Erlinda G. Germar, M.D.

Board Members

William T. Lavadia, M.D. Esperanza Cabral, M.D. Evelyn Gonzaga, M.D. Edgardo Tolentino, M.D. Julita R. Jalbuena, M.D.

Immediate Past President

Ma. Trinidad R. Vera, M.D.

Committee Members

President Ma. Trinidad R. Vera, M.D. Committee Members Chairman Committee Members Reviewers Ma. Trinidad R. Vera,

Chairman

Committee Members

Reviewers

Ma. Trinidad R. Vera, M.D.

Leonardo A. Almeda, M.D. Florante P. Gonzaga, M.D. Corazon T. Lim, M.D. Santiago A. del Rosario, M.D.

Sylvia A. Carnero, M.D. Lyra Ruth Clemente-Chua, M.D. Erlinda G. Germar, M.D. Julita R. Jalbuena, M.D. William T. Lavadia, M.D. Lilia P. Luna, M.D. Eileen M. Manalo, M.D. Delfin A. Tan, M.D. Ma. Hilaria R. Vera, M.D.

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PSCM Guidelines for Clinical Practice for Management of Menopause

   

MISSION STATEMENT

Hormone Replacement Therapy

The Philippine Society of Climacteric Medicine (PSCM) believes that menopause is a state of hormone deficiency that should be treated. Our mission is to ensure that women receive appropriate guidance and medical management during their menopausal years. The purpose of these guidelines is to provide a reference source for the evaluation and treatment of the menopausal state. In the Philippines, fewer than 10% of the postmenopausal women currently receive hormone replacement therapy (HRT).

In the management of the menopausic patient, the timing of medical evaluation and intervention is somewhat arbitrary and dependent on the issues that prompt a patient to seek a consultation. If the woman is apparently fit and healthy with no complaints, it is better to leave her at that. The most common symptoms at the time of initial assessment of the menopausal patient are vasomotor instability, mood swings, insomnia, decrease libido and cessation of menses or irregular menses, usually associated with shortening of menstrual cycles. Other patients, because of self-education and media exposure, consult a physician to explore their own risk factors and the preventive health issues that HRT can address. Despite these differences in symptoms and issues of interest to the patient, a standard of approach should be used for the assessment of the menopausal woman.

DIAgNOSTIC EvALUATION

This documents consists of recommendations for the clinical management of menopause and is intended for use by physicians to support their treatment of women’s reproductive health issues. We recognize that these guidelines should be used in conjunction with the best clinical judgement and the patient’s individual needs. These guidelines will be revised and updated periodically to reflect the latest developments in the management of menopause.

INTRODUCTION

The initial consultation is not only the time for eliciting the history, performing a physical examination, and ordering appropriate studies but also an opportunity to educate the patient. To make a rational decision about whether to use HRT, the patient must have a thorough knowledge about the benefits and risks of taking sex hormones. In this context, the patient’s knowledge, attitude and perceptions regarding menopause and perimenopause as well as her ideas about management must be explained to provide diagnostic perspective, reveal biases, and present a basis for optimizing adherence to eventual recommendations.

Menopause is customarily defined, for statistical and epidemiologic purposes, as the absence of menses for 1 year. This definition, however, is merely a guidepost in an ongoing process of declining ovarian function, usually beginning by age 35 to 40 years, with the resultant hormone deficiencies causing progressive systemic damage. Menopause is adult-onset ovarian failure, with the loss of estrogens, progesterone, and ovarian androgens.

HISTORY

The loss of estrogens can lead to vasomotor symptoms, sleep disturbances, mood alterations, depressions, urinary tract and vaginal atrophy, and increased health risks for several chronic disorders including osteoporosis, cardiovascular disease, and loss of cognitive function. Thus, both the organic and the psychologic consequences must be addressed. Perimenopause is a clinically pre-defined interval that begins with sporadic abnormalities or failure of development and function of the ovarian follicles, corpus luteum or both. It progresses to persistent anovulation, loss of production of progesterone, and erratic secretion of estrogen. The earliest evidence for ovarian failure is a gradual increase in plasma gonadotropin levels, manifesting as early as age 35 years as a minimal elevation of follicle-stimulating hormone (FSH) in day 2 of the menstrual cycle.

The history should routinely include the following informations:

• A detailed chronologic reproductive history including time of menarche, gravidity and parity, history of breast-feeding, gynecologic surgical history, and a detailed menstrual history

• History of hormonal treatment, including contraceptives, estrogens, progesterone, and androgens.

Detailed sexual history, including frequency of intercourse, ease of arousal, libido, orgasm and dyspareunia. • Symptoms of pelvic floor relaxation and bladder dysfunction

• Bone or joint pain, arthritis, fractures, osteoporosis

• Loss of height

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• General current and past personal medical history, family history, and social history

• History of lactose intolerance and achlorhydria

• History of weight fluctuations, physical activity, and exercise tolerance

• Quality-of-life assessment, psychiatric history, premenopausal mood disorders, pre-menstrual dysphoria and cognitive functioning.

• Family history, especially of early menopause, cardiovascular disease, osteoporosis, cancer and dementia

• Dietary history with emphasis on intake of sodium, vitamins (especially Vitamin D) and calcium

• Medications (e.g. corticosteroids)

• Understanding of fears and expectation surrounding menopause.

PHYSICAL ExAMINATION

As part of the comprehensive physical examination, particular attention should be paid to the following:

• Posture (signs related to osteoporotic compression changes), gait, muscle tone, coordination, height and body proportions

• Body mass index, body composition, and waist circumference

• Breast examination

• Pelvic examination, which should include size and shape of the uterus and adnexal structures, evaluation of estrogenic status of the vaginal mucosa, elasticity and thickness of the vaginal wall (discharge, atrophy), integrity of the pelvic floor (cystocele, rectocele) and levator ani function

• Eyesight and hearing acuity (in terms of fracture risk, quality of life)

LAbORATORY STUDIES

1. Hormonal Evaluation

• D 2 or D 3 serum FSH (levels of >10-12 mIU/mL) indicates diminished ovarian reserve. Levels >40 mIU/mL is associated with menopause.

• Estradiol level <30 µg/mL

• Testosterone, DHEAS

• Serum thyrotropin (hyperthyroidism is common in menopausal patients)

2. Special Baseline Studies

The following studies may be necessary or useful at the time of initial assessment;

• Pap Smear

• Mammography

• Bone Density Measurement

• Assessment of Endometrium

• Pelvic Ultrasound Scanning

THERAPY

All women should consider HRT not only as essential replacement of missing hormones but also as a type of preventive medicine. The risks and benefits of HRT should be individualized in the basis of quality-of-life consideration and a personal risk assessment, with consideration of cardiovascular, osteoporosis, dementia and cancer risk factors. Therefore our mission should be to educate women and fill this void relative to the health benefits of HRT and to convey the proper balance of risk versus-benefit information.

The aim of the first consultation must be to ensure that the patient has an understanding of the risks and benefits of both short-term and long-term therapy, and that the doctors appreciates the woman’s particular needs and goals.

How long can HRT be given safely?

Although there is considerable evidence about the health effects of long-term use of HRT, recommendations about long-term use of HRT are more difficult. For many women the benefits of long-term HRT use will outweigh

the risks; for others, risks outweigh the benefits. The use then of HRT has to be tailored to the needs and desires

of the individual.

What are the long-term goals of HRT?

They are:

• Relief of subjective and objective symptoms

• Prevention of osteoporosis

• Prevention of cardiovascular disease

• Prevention of dementia

• Prevention of carbohydrates intolerance

• Prevention of Osteoporosis

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increase bone fragility and therefore its

susceptibility to fracture. Low bone-mineral density is associated with increase risk of fracture, and women in the lowest quartile of bone-mineral density have

a 12-fold increased risk of hip fracture. The lifetime

risk of fragility fractures in a 50-year-old woman is 30-40%. In healthy women, there is only slight bone loss before the menopause. The menopause induces accelerated bone loss within 5-6 years, followed by a linear rate of bone loss that may accelerate after the age of 75 years. Postmenopausal bone loss is related to an increase of bone turnover that is estrogen dependent,

even in the elderly.

Women usually begin HRT early after the menopause

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and often stop after a few years, whereas most osteoporotic fractures occur after age 65. Long-term use is necessary to decrease substantially the incidence of fractures:

Several placebo-controlled trials over 2-3 years have shown that HRT prevents bone loss in women in the early and late menopause. Although the size of the effect varies between the sites measured, HRT is effective throughout the skeleton. HRT reduces serum & urinary markers of bone-turnover, which return to premenopausal values. Doses of 0.625 mg conjugated estrogens, 1-2 mg 17 estradiol, and 50-100 micrograms of transdermal 17 beta estradiol are effective with less than 10% of women showing bone loss. Recently, it has been found that smaller doses prevent bone loss, specially in the late postmenopausal period. The type of progestogen added to the regimen does not affect the skeletal response to estrogen, with the exception of some compounds with androgenic effects, such as norethisterone acetate which has an anabolic effect on bone tissue. Current use of HRT, specially long-term use, is associated with a 30-50% reduction of hip, spine and waist fractures, but past users are not protected. After HRT is stopped, bone loss resumes within a year and bone turnover increases to the level of untreated women within 3-6 months which probably accounts for the lack of fracture protection in past users. The addition of calcium and of Vitamin D to HRT, maybe beneficial, specially in elderly women. The combination of HRT with either another antiresorptive drug (such as a BIPHOSPHONATE) or a bone-forming agent is an interesting possibility that should be explored.

• Cardiovascular Disease

Cardiovascular disease remains to be the leading cause of mortality among Filipinos (39.4%) with coronary heart disease as the single leading cause of death and significant cause of morbidity among women.

Although a cause and effect relations is not proved, evidence that HRT lowers the risk of coronary heart disease in women without a history of this disease is sufficiently strong to consider this potential benefit when deciding to use HRT.

HRT raises the risk of venous thromboembolism, but the absolute risk is small in women without predisposing conditions.

Several meta-analysis of observational studies have demonstrated a 35-50% lower relative risk (RR) of cardiovascular mortality in HRT users relative to non users.

The mechanism of estrogen-related cardiovascular

protection include the following factors:

1. improved lipid profile, with increased high-density lipoprotein (HDL) cholesterol, decreases low density - lipoprotein (LDL) cholesterol and decrease total cholesterol. 2. potentiation of endothelium - derived relaxing factors (nitric oxide) leading to coronary artery vasodilitation. 3. antioxidant effect in LDL cholesterol, reducing plaque formation 4. reduction of serum fibrinogen 5. calcium channel blocking effect 6. increased prostacyclin biosynthesis

The one completed large randomized trial is HERS (Heart and Estrogen/Progestin Replacement Study published in 1998), a trial among women with coronary heart disease. Continuous combined therapy of 0.625 mg conjugated estrogen and 2.5 mg MPA was compared with placebo. Over a mean of 4.1 years follow up, this trial reported no net effect of HRT on recurrence of coronary heart disease, but there was a significant trend for decreasing risk with longer duration. Risk was unexpectedly substantially increased in the first 4 month in the HRT group, followed by a decline to a relative risk of 0.67 in the final 2 years. The same pattern of an early increase in risk, followed by a late decrease, was found in the setting of secondary prevention in the Nurses Health Study Control. These findings raise concern about prescribing hormones to women with a prior myocardial infarction, but do suggests long term benefit.

The effects of HRT on stroke risk are uncertain. The weight of evidence suggests neither a decrease nor an increase in risk.

• Dementia

Dementia (loss of intellectual functioning) affects 10% of women older than 65 years and 50% of women older than 85 years. Alzheimer’s diseases is 2 to 3 times more likely to develop in women than in men. The risk of developing Alzheimer’s disease is 50% lower in ever users, than in one users of HRT (RR=0.5) This effect crosses genetic phenotypes and socio-economic class; however, lower biologic intelligence increases the risk for Alzheimer’s disease. A meta-analysis of the observational studies of the effect of estrogen therapy on the risk for developing dementia did support a 29% decreased risk among estrogen users. If validated by scientific studies, the risk reduction would be of major public health importance.

The role of HRT in the treatment of Alzheimer’s Disease is still highly debatable. What is known is that it is more putative rather than curative. It can ameliorate

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symptoms of dementia by increasing cerebral blood flow and glucose utilization, at the same time lessen anti-inflammatory effects of the degradation products of beta-amyloid proteins. It is a mood stabilizer in that it enhances the production of nor-adrenaline, the deficiency of which is implicated in certain types of depression.

• Prevention of Carbohydrate Intolerance

The menopause is a diabetogenic state. After the cessation of menses, reduced levels of estrogen are associated with an increase in insulin resistance. Insulin resistance in turn and the resultant hyperinsulinemia predispose to lipid abnormalities and increase the risk of atherosclerosis. This helps explain the close association of diabetes mellitus with coronary heart disease. About a decade ago, diabetes mellitus was considered one of the relative contraindications for use of hormone replacement therapy. Recent data suggest that use of hormone replacement therapy is safe for the postmenopausal diabetic women.

Various studies have shown that HRT is associated with a decrease in the likelihood of developing diabetes by a factor of nearly 5; improves blood glucose control, and is associated with a decrease in the risk of MI in women with diabetes (RR = 0.51; 95% confidence interval 0.22 to 1.15 overall and RR = 0.78; 95% CI 0.56 to 1.08 per year of HRT use). HRT reduces insulin resistance and may be administered continuously and safely.

How should the woman on HRT be monitored?

What do we monitor? The response of the patient to treatment and the development of complications. Special baseline studies not done at the initiation of treatment must be done during the first year of HRT.

HRT associated with uterine bleeding is a major cause for poor compliance. How do you go about with this problem?

Most postmenopausal HRT regimens lead to endometrial bleeding. However, the response to any one regimen varies greatly from every individual. The response of women will depend on the estrogen and progestogen dosages, the regimen and route by which these are administered and their respective potencies. The role of vaginal sonography, hysteroscopy and endometrial biopsy is emphasized to monitor changes in the endometrium or other causes of postmenopausal bleeding. Patients should be appropriately counselled.

How then is HRT administered with regards to its main clinical goal taking to consideration its contraindications?

The main clinical goal of HRT (estrogen, progestogen) is to alleviate the symptoms of menopause. It can be administered orally, transdermally, topically, internally or as subcutaneous implants. In a woman with a uterus, HRT must include an estrogen and a progestational agent because the use of estrogen alone can produce endometrial hyperplasia or carcinoma (or both). In the absence of a uterus, a progestational agent is unnecessary. In patients with a subtotal hysterectomy, it is always prudent to start the patient on sequential type of HRT for at least 3 months, if with bleeding you can continue giving your estrogen & progestogen continuously, combined. If no bleeding the giving of estrogen alone is sufficient.

• Estrogens

The following are the most commonly used estrogens:

- conjugated equine estrogens

- Esterified estrogens

- Estropipate and other estrone sulfate preparation

- micronized 17 B- estradiol

- transdermal estradiol patches

- vaginal estrogenic preparation including a vaginal ring

- Ethinyl Estradiol

In addition, other available preparation such as estrogen pellets, gels, creams, intranasal sprays or injections (Depo-Estradiol) have been used. The major differences among these formulation are in the mode of absorption and the pharmacokinetics. Few, if any, clinically significant qualitative differences exists between free and conjugates estrogens.

The oral & transdermal routes are the most frequently used. Patient acceptance and prior experience are the major factors in determining the preferred route of delivery. The oral route is distinguished by first- pass enterohepatic removal of a substantial fraction of the estrogen, followed by hepatic metabolism and conjugation to sulfates and gluconomides, which are then excreted through the bile back into the digestive tract. Here, the sulfates are deconjugated to some extent and reabsorbed. All drugs subject to the first- pass effect show greater interindividual variability, in the blood levels attained. This findings is true of the estrogens - a fact that is of considerable clinical relevance. Furthermore, the high concentration of estrogen delivered to the liver by the oral route (in comparison with transdermal absorption directly into the peripheral circulation) induce increased synthesis

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of triglycerides and certain proteins such as cortisol- binding globulin (transcortin), sex hormone-binding globulin and angiotensinogen. Therefore, transdermal estrogen is preferred in certain clinical situations, such as in women with hypertension, hypertriglyceridemia, and a history of an increased risk for cholelithiasis.

Vaginal administration of estrogen has been used for treatment of vaginal atrophy. Estrogens are readily absorbed through the vaginal mucosa and result in appreciable blood levels of estrogen.

The dosage of estrogen used to initiate HRT should be individualized because it is strongly dependent on age of the patient and various others factors. In a reproductive - age woman who had recent bilateral oopherectomy, a larger dosage of estrogen (e.g. orally administered micronized estradiol 2-4 mg/day; equine estrogen 1.25 - 2.5 mg/day; or ethinyl estradiol 0.02 - 0.05 mg/day) is required than for a woman who has been amenorrheic and symptomatic for a long time (e.g. orally administered micronized estradiol, 1-2 mg/day, transdermal estradiol 0.05-0.1 mg/day; equine estrogen 0.625 to 0.9 mg/day, or ethiyl estradiol 0.01 to 0.02 mg/day. A patient who has been deprived of estrogens for years is likely to be too sensitive to the usual dosages and should initially receive even lower doses than those used for maintenace therapy. The desired effects of therapy manifest themselves slowly.

• Progestins

After hysterectomy, progestins are unnecessary. In a woman with an intact uterus, the endometrium must be protected against hyperplasia and possible progression to dysplasia and carcinoma by the use of progestational agents.

The classic regimen consists of 5 to 10 mg of medroxyprogesterone acetate (MPA) used for 10 to 14 days each month. Levonorgestrel, norethindrone, or micronized progesterone can also be used for this purpose. Cyclic administration of the progestins usually produces monthly menstrual periods. Because persistent menstrual bleeding is often cited as the major reason for non-compliance with HRT, amenorrhea maybe achieved by using a low dose of a progestin administered continuously (daily) in conjunction with estrogen. Some women, however, will continue to experience episodes of breakthrough bleeding. Alternatively, a progestin can be administered at 2, 3 or 6 month intervals and still prevent endometrial hyperplasia. This non-conventional use of progestin requires careful monitoring of the endometrium with ultrasonography and endometrial biopsy.

Micronized progesterone has been shown to be an

effective alternative to MPA in dosages of 100 to 200 mg daily. Reported outcomes here included <1% incidence of hyperplasia and improved lipid profiles.

• Androgens and Anabolic Agents

Does an androgen-deficiency state exist in postmenopausal women? The menopausal ovarian stroma continues to produce testoserone and androstenedione in response to increased pituitary gonadotropin stimulation. With advancing age, however, adrenal androgen production gradually declines. Bilateral oophorectomy in premenopausal, perimenopausal, or postmenopausal women leads to approximately 50% reduction of testosterone levels. The initiation of HRT leads to a suppression of gonadotropins, and a decrease in ovarian androgen production. In addition, estrogen stimulates the production of sex-hormone-binding globulin thereby leads to decreased free testosterone. Therefore, menopausal women receiving HRT have a loss of androgen effect in comparison with the premenopausal state. Sexual dysfunction, loss of libido, depression, decrease energy, and other symptoms have been attributed to the loss of androgen production. Observational and cross sectional studies of postmenopausal women have generally failed to demonstrate a correlation between circulating androgen levels & libido.

The androgen preparations commonly used include methyltestosterone, parenterally administered testosterone; transdermal patches, and orally administered micronized testosterone as well as DHEAS. The most widely used oral androgen formulation is Methyltestosterone.

Methyltestosterone dose used is 1.25 to 2.5 mg/day DHEAS-25 to 100 mg/tablet Micronized testosterone for oral use is 2.5-5.0 mg in vegetable oil capsule.

In general, side effects of excessive androgen therapy, including seborrhea, acne, hirsutism, alopecia, voice changes and clitoral hypertrophy, are dependent on the dose, duration and individual patient. Androgen may alter the HDL/LDL ratio by lowering HDL levels.

Four general groups of women are considered candidates for estrogen + androgen therapy:

1. women who have had their ovaries removed 2. those who have not experienced relief of vasomotor symptoms with a maximally tolerable dose of estrogen 3. Those at risks for osteoporosis in whom other modalities are not satisfactory or suitable 4. Those with unsatisfactory sexual functions, especially loss of libido.

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Because no consensus exists about the use of androgen therapy, the potential benefits and risk should be explored for each patient.

What are the adverse effects and contraindications to the use of HRT?

Adverse effects of HRT

1. Increased risk of thromboembolism, usually occuring within the first year of therapy, that applies to all forms of estrogen. Women who have had documented deep vein thrombophlebitis or pulmonary embolism in the past should, most probably, not be prescribed any form of HRT.

2. Increased risk of cholelithiasis has been found in women who use orally administered estrogens.

3. Increased risk of breast cancer for women taking HRT >10 years, which applies to all forms of estrogen.

Contraindications to use of HRT

1. A history of breast cancer is still the main contraindication.

2. Previous venous thrombo embolism

3. Undiagnosed genital bleeding

4. Gall Bladder disease

5. Hypertension

6. Migraine and other headache

HRT AND RISk Of CANCER

About 1.5 million cancers are diagnosed annually in women and almost half are cancers of the reproductive organs. Over 80% of the cancers occur in postmenopausal women. Breast cancer is the most common (422,000 cases), and the risk increases with earlier menarche and later menopause).

Based on a reanalysis of data on 51,000 women with breast cancer and 108,000 controls (from 51 worldwide studies) the collaborative group in hormonal factors in Breast Cancer reported that ever-use of HRT was associated with an overall 14% increase in the relative risk of breast cancer, with no heterogeneity between studies. The excess risk was largely confined to current and recent users, in whom the relative risk increased by 2.3% for each year of use. This increase is roughly equivalent to the increased linked to a 1-year delay in the menopause. Overall, use of HRT for 1-2 years is associated with no risk. By 5 years after stopping HRT, the effects in breast cancer risk has essentially disappeared. About 80% of the users were on estrogen only preparation.

The excess risk was mainly confined to localized breast cancers. Collaborative Group and a recent report from

the Iowa Women’s Health Study showed that the cancers were less aggressive and survived longer in HRT users than in non-users, which may be a biological effect of the hormones or because the cancers are detected earlier in HRT users. To put the collaborative Group data absolutely, the cumulative excess incidence in 1000 women who used HRT for 5 and 10 years starting at age 50 is 2 and 6 cases respectively. In the collaborative group analysis, the increased risk of breast cancer associated with HRT is mostly restricted to leaner women.

In 1999 case-control study from Sweden of about 3,000 women with breast cancer showed a higher relative risk: odds ratio of 1.65 for ever versus never users of estrogen or estrogen/progestogen preparation. There was a statistically significant trend for increasing risk with increasing duration to use.

Colorectal cancer is the second most common cancer in women in developed countries. The overall relative risk of this cancer associated with ever-use of HRT was, from 14 observational studies, 0.8-ie, a protective effect. The relative risk for current users was 0.7 and for past users, 0.8 although the date for past users are very heterogenous.

An association of endometrial cancer and HRT with estrogens alone has long been recognized, and was the reason that progestogens were added to the regimen. An overview of four studies that looked at ever-use of a combined preparation showed a relative risk of 1.3.

Cancer of the cervix and HRT - HRT maybe offered to patient with cervical cancer.

Cancer of the ovaries and HRT - HRT maybe given safely after surgical management of the ovarian cancer.

Vulvar cancer and HRT - no information

There is two little information to comment on any link between HRT use and other concerns.

HRT in women with a history of breast or endometrial cancer

Should HRT be given in patients who have had breast or endometrial cancer? There are no data to answer this question adequately. In six retrospective series ( total of 490 patients), the rate of recurrence of breast cancer in women on HRT was 0-9%, with 0-6% deaths. Thus, HRT should be prescribed only after the woman has been advised to the uncertainty about risk.

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Management when HRT cannot be used

Alternatives are available when HRT is contraindicated or not tolerated. These options are:

1. Selective Estrogen Receptor Modulators (SERM)

- these have a selective estrogen like activity

on some tissues and anti-estrogen activity on

other estrogen- responsive tissues. Raloxifene has been approved for the prevention and treatment of osteoporosis in postmenopausal women. In the (MORE) Multiple Outcomes of Raloxifene Evaluation study, approximately a 50% reduction in vertebral fractures was noted at 24 months and

a 40% reduction at 36 months in women with

osteoporosis. The study was not statistically proved

to assess hip fracture. Like estrogen raloxifene lowers

LDL levels: However unlike estrogen, raloxifene does not increase total HDL levels or triglycerides. Cardiovascular disease prevention trials are currently being conducted (RUTH) Trial Raloxifene use for the heart, to determine whether raloxifene reduces the risks of cardiac events. Early studies suggest that Raloxifene may significantly reduce the risk of breast cancer. A comparison study with tamoxifene is underway to analyze these findings further. Unlike tamoxifene, Raloxifene does not stimulate the endometrium and can be used for women with intact uterus. Raloxifene does not relieve hot flushes and in fact may increase their occurrence; therefore it will not benefit perimenopausal women with vasomotor symptoms. The incidence of deep venous thrombosis associated with use of Raloxifene is similar to that with estrogen. 2. Phytoestrogens - may act as selective estrogen modulators and are currently being studied. 3. Alendronate, a biphosphonate has been shown to decrease significantly the risk of osteoporotic fractures in the hip and spine. In the Fracture Intervention Trial (FIT) a 40-50% decrease in spine, hip and waist fractures was noted at 3 years in women with previous fractures given Alendronate. 4. Calcitonin - is available in nasal spray form for treatment of osteoporosis. In the current Prevent Recurrence of Osteoporotic Fractures (PROOF) Study, a 37% reductions in vertebral fractures was noted at 5 years in postmenopausal women with osteoporosis. 5. In general, sufficient calcium, vitamin D, and exercise are important factors in helping to maintain bone density. Exercise is also important for maintaining muscle tone and helping to reduce the risk of falling.

CONCLUSION

In the use of these guidelines to assess and manage

perimenopausal and menopausal women, the primary goal is to inform the patient as completely as possible about the benefits and risk of HRT. Although HRT is preventive medicine at its best, its use-like all issues in preventive medicine - is elective. Menopausal women will comply with HRT if they are confident in their decisions, receive continued support and encouragement for adherence, and accept the potential adverse effects and risks in comparison with he benefits.

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menopausal Women, 1999.

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HORMONE REPLACEMENT THERAPY

CPM 4 TH EDITION

Drugs Mentioned in the Treatment Guideline

       

This index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing Information of these drugs can be found in the Philippine Pharmaceutical Directory (PPD) 8 th edition. Opposite the brand name is its page number in the PPD 8 th edition.

     

biphosphonates

 

Kliogest Trisequens* Estriol Ovestin Estrogen-Conjugated Premarin Estrogen-Conjugated/ Medroxyprogesterone acetate (MPA) Premelle 2.5/Premelle 5 Premelle Cycle 5 Estrogen-Conjugated/ Medrogestone Prempak Ethinylestradiol/ Cyproterone acetate

 

P227

 

Proluton Depot Lynestrenol Exluton Medroxyprogesterone acetate (MPA) Depo-Provera Provera Norethisterone Primolut N Noristerat

P228

Alendronate

P228

Fosamax

Q231

P228

 

P226

Calcium Preparations Agre-Calvit (Reformulated)* Anlene Gold Hi-Calcium Nonfat Milk Anlene Hi-Calcium Low Lactose Anlene Hi-Calcium Nonfat Milk Athena Hi-Calcium Nonfat Milk for Women Calcebone Calci-Aid Calciumade Calcium-D-Redoxon* Calcium Sandoz Calcium Sandoz + Vit C* Calsan Caltrate Plus* Carnation Calcium Plus Carnation Non-Fat Tridin* United Home Ca Lactate

 

P226

P228

K161

P228

K183

P228

P227

P230

K183

P227

 

K183

 

Selective-estrogen receptor modulator (SERM) Raloxifene Evista Tamoxifen Cox Tamoxifen Kessar Nolvadex/Nolvadex-D Tamoplex Tamoxsta Zitazonium

 

P227

P227

K183

K161

Diane-35

     

P226

E72

K161

Ethinylestradiol/ Desogestrel Gracial Marvelon 28 Mercilon Ethinylestradiol/ Gestodene Gynera Meliane Minulet Ethinylestradiol/ Levonorgestrel Logynon Microgynon 30 Nordette E 21 Rigevidon 21 + 7 Trinordiol Tri-Regol Ethinylestradiol/ Norethindrone Micropil Ethinylestradiol/ Norgestrel Femenal

 

E72

K183

E73

K161

 

P229

E73

K161

P229

E73

P229

E73

K161

   

K161

 

vitamin D & Derivatives Agre-Calvit (Reformulated)* Calcium-D-Redoxon* Caltrate Plus* Cod Liver Oil Forte* Alfacalcidol Alpha D 3 Calcitriol Rocaltrol

 

K161

 

P229

K184

P229

K161

K184

P230

K161

K161

 

K161

K158

K161

 

P229

 

P229

 

Q231

 

Calcitonins

P230

 

Salmon Calcitonin

P230

K158

Miacalcic

Q231

P230

 

Tonocalcin

Q231

P230

 

P230

Estrogens Estradiol Climara Estraderm MX Estrofem Progynova Estradiol/ Cyproterone acetate Climen Estradiol/Dydrogesterone Femoston Estradiol/Norethisterone acetate Estracomb TTS

P225

 

P226

 

P230

P226

 

P226

 

P229

P226

Progestogens (Progestins) Allylestrenol Turinal Dydrogesterone Duphaston Hydroxygesterone caproate

       

P227

P228

P228

P227