Sunday, May 19, 2019

MEDICAL TREATMENT OF MENOPAUSE


MEDICAL ADVICE
            Seeking good medical advice at menopause is important so that you can make the most of this remaining post menopausal time of your life happy and healthy. Many women will benefit from hormone replacement therapy (HRT), depending on various risk factors and the presence of any chronically debilitating ailments. To get the most benefit it is wise to seek your doctor’s advice as early as possible. Women in their 40s will benefit from a routine medical consultation and examination which can detect any serious problems such as high blood pressure, diabetes and breast cancer. Advice on HRT, cancer diagnosis, life style factors, can be provided at this time. The menopausal time frame is divided into three periods; (1) premenopausal:- that is just before menopausal years and menopausal symptoms that have not yet started to bother you.(2) The  perimenopause;- This can last for many years, women may start to have many symptoms at this time, for example, infrequent or frequent periods, heavy or scanty periods and many general problems which  can be seen in the chapter on  symptoms of menopause. They are hot flushes, cold sweats, dry vagina and many any others. (3) The final period is called postmenopausal after a woman has not had a period for 12 months.
            HRT represents the greatest breakthrough in the health care of women during menopause. When this treatment is combined with changes in lifestyle, a healthy diet, adequate exercise and good medical advice, women can look forward to many fulfilling and happy years.
            HRT (now called MHT) is a way of replacing your lost or deficient hormones after the natural decline of ovarian hormones or surgical removal of the ovaries. HRT consists of varying amounts and forms of oestrogen, progesterone, and sometimes testosterone. The main component of HRT is oestrogen. Progesterone’s main role in the treatment is to counterbalance the risk of endometrial cancer caused from unopposed oestrogen (oestrogen used alone). Of much lesser importance in the trinity of HRT is testosterone which mainly improves sexual function. Your doctor can start treating you with HRT to relieve your symptoms, most commonly hot flushes, mood swings or a dry vagina as well as preventing long-term adverse effects of menopause such as heart (cardio vascular) disease, osteoporosis and genital atrophy (shrinkage of the vulva and vagina). Although HRT has been around, in various forms for about 80 years, it has only gained popularity in the last ten years because of improved understanding of its appropriate use and the recent emphasis on women’s health. In 1821 a male French physician gave the name La Menopausia, or the Greeks called it the end of periods (Meno , Pause). Before this it was often called hysteria and horrible , disgusting treatments were offered. Women were given opium, cannabis, belladonna, terrible vaginal and vulval injections and hideous concoctions to drink. Women became hysterical and the disease was named Hysteria.
HISTORY OF HRT
When it was learned that it was the lack of oestrogens, which caused the problems with menopause,  as a result of this, in 1941 hormones prepared from the pregnant mares urine called Premarin where released for human use. In 1966, one physician wrote a book called FEMININE FOR EVER. Then there was no end to the use of oestrogens. The women and their partners were very happy, but then in 1970 endometrial cancer raised its ugly head. In 1970 The International Menopause Society was established. The first international congress on menopause was held in PARIS. In 1977 many books were published called “Women and Crisis in hormone health”by different auothers. This controversy continued for a long time. Since then many studies have been done to assess the benefits of HRT on women’s health, particularly about Cardiovascular Disease, Cancer, Osteoporosis and Quality of Life. But constantly there was concern about benefit/risk ratio running in parallel. In many of these studies the selection of women was not so good, women of all ages were included (50-79) mainly in the biggest study THE WOMENS HEALTH INITIATIVE which started in 2001 and is still continuing. However I am very pleased that HRT is now received very favorably around the world in most countries, many risk factors have been resolved.
Your initial medical consultation for advice
When and why to go to your doctor
            On the initial visit, your doctor will take your medical history, perform an examination and relevant tests and provide counseling about whether to start HRT. Even if you have never had a medical check-up and are, in your 60s, you should still seek advice from a doctor at this period of your life, although it is best to seek advice around 40.
            This consultation will help the doctor to assess if you’re an appropriate candidate for HRT. Your doctor will discuss with you the benefits and any possible side-effects to enable you to decide whether or not you should consider HRT. An examination will help rule out any cancer (especially breast cancer), diabetes, high blood pressure and any number of Gynecologic conditions. Cancers which need to be ruled out include breast cancer, as well as ovarian, uterine and cervical cancers. The most common non-cancerous gynecological conditions in women of this age group are prolapse of the pelvic organs, urinary difficulties and fibroids of the uterus. Disorders of the thyroid gland (usually under activity)] are also common at the time of menopause.
         It is important to choose a general practitioner who is well informed about this area of medicine. Referral to a specialist may be necessary for dealing with more complex or difficult problems. You can also attend a menopause clinic.
 What to expect at your first consultation
            The treatment of menopause starts with a thorough medical history and clinical examination. A few blood and radiological investigations can provide additional useful information. Your doctor will take a family history which should focus on heart disease, stroke, cancer, osteoporosis, deep venous thrombosis, and diabetes. The clinical examination should include checks for height and weight, blood pressure as well as a breast and heart examination. A pelvic examination including a smear test is done. Smear  test, in recent years in younger women is not always required, if they have had, the vaccination for the Human Papilloma Virus (HPV) which is now available in many countries as a protection against cervical cancer. Breast cancer must also be excluded by clinical examination; a mammogram should be performed if thought reasonable. It is also good practice to have a rectal examination, and also to get your stools examined for blood, as bowel cancer is common in this age group.
            A consistently high level of follicle stimulating hormone (FSH) will confirm menopausal status although treatment can be started on the basis of a woman’s symptoms if the woman is younger than 40. FSH or a pregnancy test is required. Assessment of bone density is not routinely ordered; however, the present view is that they should be done at the initial medical assessment. The need for repeat testing will vary from woman to woman. A low bone density with the associated higher fracture risk will often lead women to choose HRT for this reason alone.
An ultrasound of the pelvis is particularly useful if you are overweight, or if a normal pelvic examination is difficult or if a pelvic disease is suspected on clinical examination. Ultrasound can confirm or detect uterine polyps, fibroids or ovarian cysts. In addition, some institutions use ultrasound to assist in the screening of ovarian cancer
In situations of irregular bleeding, especially in women over 60 years, it is useful to assess the thickness of the endometrial cavity and check for uterine polyps. This investigation can be done by transvaginal ultrasound and may prevent the need for more invasive diagnostic surgical procedures (such as curettage)
   After examination and investigations, women are generally counseled about their various medical options and the achievable goals for a healthy lifestyle. Your doctor will caution you about possible side-effects of HRT before you make a decision.
Generally, your doctor will want to see you again within two months, after the initial consultation, in order to tailor the HRT dose and to manage any side effects such as uterine   bleeding or tender breasts. If you have any side-effects, consult your doctor, but do not stop treatment. Up to twelve months may be necessary to establish a satisfactory HRT dose combination.

Who should take HRT?
   The decision to take HRT is an individual one. In general all women who are suffering from oestrogen deficiency symptoms, who are at risk of heart disease or osteoporosis, or who already have osteoporosis, will benefit from HRT. Women who have had premature ovarian failure, surgical menopause, or long periods of amenorrhea will especially benefit from HRT as the period of oestrogen deficiency begins earlier for them.
     After discussing treatment options with your doctor and making an informed decision about whether to start hormone replacement therapy, you will be prescribed HRT according to your health profile. You wil1 usually start with average doses which are then tailored to your needs depending on your response.
     In three to seven days the symptoms of hot flushes and mood changes will improve. Generally, within three to six months your doctor will achieve a happy balance between symptom relief and side-effects by choosing the appropriate therapy combination.
      What combination of HRT is most suitable for you depends on your age, your predominant symptoms, your desire to continue with regular periods, the presence of any risk factors, and if you have had a hysterectomy, with or without the removal of your ovaries, and the reason for the hysterectomy.
Follow-up visits to your doctor
         After starting HRT, it is recommended that you see your doctor every two months until you are satisfied that the therapy is keeping you free of: symptoms and side effects. It is then sufficient to have yearly checkups, involving a breast, blood pressure and pelvic examination. A cervical smear test is recommended every two years for postmenopausal women. After the initial scan to study your bones for osteoporosis, another is recommended every two to five years depending on your bone health.
Presently, a mammogram is recommended every two years for women 50 to 70 years old for the detection of breast cancer. This does not replace breast self-examination or a clinical one by your doctor. You should continue to practice this preventative monthly check.
            Some authorities recommend an annual endometrial biopsy for women on long-term HRT. A transvaginal ultrasound can also solve this problem by measuring the endometrial thickness, this test and or biopsy, are especially important if there is continuous or irregular bleeding, or for women with an intact uterus on continuous unopposed oestrogen therapy and also if a woman has risk factors for endometrial cancer. These are obesity, fibroids, diabetes, high blood pressure and never having had a pregnancy
 In summary the management of menopause requires
      General examination
      Pelvic examination
      Investigations (where appropriate)
o   blood examination
o   cholesterol and triglycerides
o   liver function test
o   follicle stimulating hormone
o   oestradiol
o   cervical cytology
o   thyroid function test
o   stool examination for blood
      Special investigations (sometimes advisable)
o   mammogram
o   bone density study
o   endometrial sample
o   bleeding and clotting profile
o   ultrasound (pelvis; right upper quadrant for gallstone and liver)
o   cardiac assessment if needed
      Psychologist  advice if needed
      Discussion                                        
      Treatment

      Follow-up
o   2 to 3 months
o   6 month
o   1 year; then yearly unless there are any special problems


BENEFITS OF HRT
1) Improved quality of life
            The symptoms such as hot flushes, mood swings, poor memory, irritability, lack of sleep, urinary problems, loss of libido and a dry vagina; are greatly alleviated with appropriate HRT. A recent study showed that women over 60 years, who had no earlier symptoms, feel an elevation of mood while on HRT. In a separate study, it was shown that there is increased production of chemicals in the brain called endorphins while on HRT which may be responsible for the mood elevation.
            While on HRT, sleep improves partly because of a decrease in night sweats and hot flushes and partly because of a direct effect of the quality of sleep.
Sexual enjoyment improves due to increased vaginal lubrication and enhanced libido. Some clinicians recommend the routine use of testosterone implants along with oestrogen when loss of libido is a problem. This is easily done if HRT is given as an implant.
            Tissues rich in collagen such as skin, muscles, joints and ligament benefit from HRT with relief of symptoms affecting them (backache, muscle and joint pains). Skin texture and thickness improves. The nails and hair improve in quality. Urinary symptoms such as frequency and pain also improve. Stress incontinence improves after several months of oestrogen usage.
2) Prevention of Osteoporosis
Prevention from Osteoporosis reduces the fracture risk by50 %


3) Reduces the risk of heart disease and possibly stroke
          This is important when HRT is started before 60years of age and within 6-10 years of menopause, as normally incidence of stroke increases any way with increasing age. Remarkably, HRT also reduces heart disease; the number one killer of women in affluent societies of older age by half. In addition, the incidence of stroke appears to be reduced, although further studies are required to confirm the degree.   
4) Slowing of ageing process
        Although HRT is not a panacea for youthful appearance, it certainly helps with excessive loss of skin tone and thinning and shrinking of vulval and vaginal areas to prevent urogenital problems. To be able to notice these changes you have to take HRT for many months.
Normally when HRT (MHT) is taken orally it is absorbed by the intestines, then it is carried to the liver from there it is passes to the target organs, heart, bones, skin and genital organs via the blood stream. While in the liver MHT changes certain enzymes, which can adversely affect the cholesterol metabolism, clotting mechanism, and cardiovascular system. To prevent these problems it is now often given as, Transdermal (via the skin) as patches, implants, gel, and creams and even by injection. From here MHT directly goes into the blood stream and from there to the target organs. This saves the changes in the cholesterol level, thrombosis, liver and gall bladder. This information has already been previously mentioned; hence it is very important to give MHT by a correct route.   
Personal History
Emotions relieved by HRT
   Claire, a school teacher, expressed her unhappiness about her changed behavior.  Over the past 12 months she had arguments with her family and friends over trivial matters. In addition, she had persistent hot flushes, night sweats, backache and sleepless nights. In the past, she had a benign brain tumor, and more recently gallstones. Her last period was 18 months ago.
            She started continuous oral oestrogen and progesterone within one week, she felt better, and within three months she was back to her normal self. She had a recurrence of gall bladder colic, which was possibly precipitated by the use of oral oestrogen. She decided to have her gall bladder removed as she believed it was important to remain on HRT. In recent times she could have been offered Transdermal MHT. It was not so easily available in the1990’s when this story happened.
Risks of Taking HRT
             HRT should not be used when a woman is suffering from cancer or has had a cancer which was Oestrogen dependent; such as breast or uterine (endometrial) cancers. The risk of endometrial cancer increases when Oestrogen is used alone for women with a uterus. This risk has now been almost eliminated with the addition of progestogen to oestrogen therapy.
HRT’s effect on breast cancer is a contentious issue because of contradictory conclusions reached by different research papers. WHI in 2001 said that Oestrogen (CEE) and medroxprogesterone (MPA) increased the risk; by 26% when this was published all women suddenly gave up there HRT. However proper analysis of the paper showed that this risk was only, 8 out of 10,000 per year, (1 extra case in 1000 per year when compared to women who had never taken HRT.
They did not mention anywhere, the fact that 8 extra cancers where saved, 2 uterine and 6 bowel cancers. A study in the USA showed that if oestrogen was taken alone in women who have had hysterectomies, there was no breast cancer in 15 years.
If you have or have had the following conditions, you should not take Oestrogens.
1.     Oestrogen-Dependent Breast Cancer
2.     Undiagnosed Abnormal Vaginal Bleeding
3.     Active Acute Liver Disease
4.     Gall Bladder Disease
5.     Chronic Liver Disease with Impaired Function
6.     Uterine Cancer
7.     Deep Venous Thrombosis, however this needs further study in the current climate, as now we have transdermal treatments which are safer.
8.     Sickle Cell Anaemia
Very rare disorder; where the haemoglobin molecule is like a sickle shape. 
      9.   Coronary Artery Disease
      10. Porphyria Rare genetic disorder of haemoglobin metabolism.
      11. Systemic Lupus Erythromatosis, rare auto immune disease where immune system attacks its own normal organs such as skin, kidney and brain.
     12. Pregnancy, make sure you are not pregnant by chance
  
If you have or have had the following illnesses, you can take oestrogens, but must have a regular check up.
1.     High Blood  Pressure
2.     Endometriosis .(Women need to take progesterone with oestrogens, if women have suffered with Endometriosis , otherwise  oestrogens  may reactivate endometriosis
3.     Smoking.
4.     Family History of Breast Cancer.
5.    Deafness  
6.     Benign Breast Disease
7.     Fibroids of the Uterus
8.     Migraine  Headaches
9.     Any Irregular Bleeding or Pelvic Pathology

Personal Story
   HRT following a History of Deep Vein Thrombosis and Pulmonary Embolism during Pregnancy
  Nazia, a doctor, 53, consulted her doctor for severe hot flushes. Low bone density was detected on a routine scan. She was concerned about taking HRT because of a past history of deep venous thrombosis and pulmonary embolism (clot in the lungs) after the birth of her child, 18 years ago.
    After discussion, she realized that HRT, in the form of oestrogen skin patches, would not change her blood clotting mechanism because the oestrogen did not bypass the liver. She was also given progesterone as a Micronized Progesterone Vaginally because she still had an intact uterus. As a precaution, she has an annual blood coagulation profile.
            In women with irregular bleeding, serious uterine disease must be excluded by ultrasound, hysteroscopy or curettage before starting HRT. It is uncommon to have a pregnancy in the menopausal age group; however it is a good idea to exclude pregnancy. This can almost always be done by clinical history and examination or pregnancy test.  Special care is needed with women who have had their menopause I year ago however it is reasonably safe if it was two years ago.
SIDE EFFECTS OF HRT
   Oestrogen and progesterone can cause some side effects for some women. In most cases, these effects diminish within two or three months; for some women, changing the form of therapy and the dosage is necessary.
 Some women experience side-effects of nausea, headaches or abdominal pain and leg cramps. In the initial therapy, the main side-effects are tender breasts (mastalgia), increased vaginal discharge, fungus, vaginal infections, irregular bleeding and heavy withdrawal bleeding. All of these side-effects can be corrected by your doctor by adjusting the dose. For example, the oestrogen dose is reduced if you have breast tenderness or heavy bleeding, and the progesterone dose is increased if you have irregular bleeding during the cycle. If irregular bleeding persists after adjusting the dosage, further investigations are necessary, such as an Ultrasound.
    After menopause and the end of the menstrual cycle, some women are loath to begin medication that will continue their monthly periods. To overcome this problem, continuous oestrogen and progesterone is now being used very effectively to prevent the recurrence of monthly bleeds. Another psychological side-effect of HRT is having to adjust to the routine of taking medication daily. You should try to organize a routine which prompts you to take your tablets regularly; smart phones are great for this.
  About 15% of women suffer side-effects such as depression and a bloated feeling similar to pre-menstrual problems from progesterone and find it intolerable to use it. In this situation, the frequency of cyclical progesterone is reduced by giving it in every third cycle .Your doctor can reduce the dose further in continuous therapy. Now for the last 20 years, micronised progesterone is available, which is well tolerated. This is available both as oral and vaginal preparations
   A gentle piece of advice and warning, never accept HRT tablets or skin patches from your friends. Remember that each prescription has been carefully formulated for each individual’s specific needs.  Your doctor will determine your own requirements over a period of time by trial and error.
Personal story.
Despite heavy smoking, having a family history of Breast Cancer and Heart Disease, HRT can be prescribed.
   Paula, 39 years old, a solicitor, was a smoker and suffered from Endometriosis. After discussion with her doctor, she had her uterus and both of her ovaries removed. Paula’s father, also a heavy smoker, died of a heart attack and her mother suffered breast cancer at the age of 53.  Paula required HRT after her operation for relief of menopausal symptoms and long-term risk of heart disease following surgical menopause.
            She was given an Oestrogen and Testosterone Implant and together with Oral Progesterone daily, due to her history of Endometriosis. Oestrogen alone could reactivate any residual Endometriosis. It was stressed to her that she needed to have an annual clinical breast examination and regular mammograms, once every two years until she was 50 years of age and then once a year thereafter. She was strongly advised to give up smoking.
Hormone Replacement and Other Diseases
Varicose Veins
  There is an erroneous belief that HRT will increase the risk of deep vein thrombosis if given to women with varicose veins. There is no proof of this and women should not be denied HRT if the need is there.
Thromboembolic disease
  There is no proof to show that oestrogen in normal physiological dose and with regular check-ups by a doctor causes deep venous thrombosis (DVT) or embolism. If there is a history of having had DVT following child birth or an operation, you can still take HRT (with Trans Dermal Oestrogens) with regular supervision by your doctor.          
In some special situations where there is a family history of DVT or if you have DVT for no obvious reason, then special blood tests such as Antithrombin III and Protein C and S, should be done before you have HRT to exclude that you have any thromboembolic disease.
Blood Pressure, Heart Disease and Stroke
   HRT can be given to women suffering from high blood pressure. It is generally preferred to have the blood pressure under control before HRT is started. Best time to start HRT is a time called the “Window of Opportunity”, that is within 6-10 years after menopause and at an age which is always under 60, so that there is no time for body tissue damage due to aging. MHT or HRT is not suitable for secondary heart disease.
Aching Legs
The cause of aching legs is poorly understood. There is no obvious reason why HRT cannot be given to you if you have this condition. If aching is only in one leg, then DVT should be excluded before starting HRT. This investigation can be done by a Doppler Ultrasound which shows the blood flow in the veins.
 Gall Bladder and Liver Disease
  Oral oestrogens can cause changes in the bile, which can cause gallstones or precipitate an attack of gall bladder colic. It can also increase triglycerides which adversely affects the pancreas. For these conditions, it may be better to use a non oral form of oestrogen.  
Migraine
  The exact understanding of the mechanism by which oestrogens and progesterones cause headache is lacking. It is believed that a migraine occurs during the menstrual period (called menstrual migraine) and is due to a lack of oestrogen. If it is so, peri menopausal women who are experiencing migraines for the first time should benefit from oestrogen. On the other hand, progesterone may cause headaches. It is better to try HRT and see how you react. It is advised to start soon after menopause, also under the age of 60.
Menopause HRT (MHT)
   HRT uses 2 main hormones mainly Oestrogens and Progestogen. In addition another hormone often required is called Testosterone. There is another group of hormones which are often used and these are called Selective Estrogen Receptor Modulators (SERMs). These have a different action with different oestrogen receptors. Some block the action of oestrogens in some areas (say in breast tissue) and enhances in another area say bones.
What form does HRT take?
OESTROGEN
     Oestradiol is by far the most common form of HRT. It comes as oral, transdermal, gel, implants, parentral and vaginal. For completion of HRT, it is combined with another hormone called progesterone. This protects the side effect of oestrogen on the uterine lining. Oral oestrogen is by far the most common form of HRT because it is inexpensive and convenient. These oral oestrogen preparations are available in various chemical formulations and strengths almost all over the world.  There are two types of oral oestrogen preparation: synthetic and natural formulations. Natural oestrogens, when metabolised in the body, mimic the body’s oestrogens. Generally, only natural oestrogens are used for HRT because they are much gentler and safer, although they are more expensive than synthetic ones. There are many different oestrogen preparations that are now marketed both synthetic and natural, the most commomly used are conjugated oestrogens,and oestradiol  preparations. Oestrogens alone only, can be used in women who do not have a uterus.

IMPLANTS (oestradiol)

       In this form, oestrogen is given as a pellet deposited under the skin by a special applicator by your doctor. The technique requires a small incision, either in the hip or abdomen to insert the implant which is about the size and appearance of a grain of sago. These oestrogen implants come in three strengths: 20, 50, and l00mg oestradiol. Generally, one 50 mg implant is inserted every six to eight months. The pellet releases oestrogen slowly. An oestrogen implant can be used after a hysterectomy when   progestogen is no longer needed to protect the endometrial lining of the uterus. It is often used in combination with a testosterone implant, if your ovaries have also been removed at the time of the hysterectomy or if you have a severe loss of sex drive.
If there is an intact uterus and require this form of treatment because of conditions such as liver disease, women will need to take progestogen tablets orally or vaginally.
Disadvantages of implants are that the dose cannot be tailored if there are any resulting side effects, and occasionally, there is a sharp surge in the oestrogen level after the initial implant. Often with implants there is an earlier return of symptoms, despite higher blood levels of oestrogens (tachyphylaxis). If this is happening, this form of oestrogen must be changed. The side effects are less pronounced if 20 mg and 50 mg
Implants are used instead of 100 mg.

 TRANSDERMAL OESTROGENS

       Skin patches are gaining popularity as a convenient form of HRT because of the small doses required with fewer side effects. Patches are useful for women with lipid problems and liver or heart disease and the risk of DVT, because the hormones go directly into the bloodstream bypassing the liver. Importantly unlike the tablets they do not increase the risk of blood clots thus preventing strokes and heart attacks. Many companies make these patches. There are patches as Oestrogen alone, Oestrogen with Cyclic Progesterone or with continuous Progesterone for different groups of women who do and do not want to have periods. Oestrogen alone should only be given to women who do not have a uterus; otherwise it runs the risk of causing endometrial thickening or cancer as previously mentioned. Women who have had Endometriosis should also be given progesterone as it can reactivate endometriosis. I have in fact seen an unfortunate case of endometrial cancer where the woman was given an oestrogen implant without progesterone after she had a hysterectomy and removal of both her ovaries for endometriosis. As with implants, skin patches are also available in different strengths.

They look like a small piece of kitchen wrap plastic which adheres to the skin and can be applied to legs, buttocks or abdomen. 
Your doctor will determine which of the available strengths and type is best suited to you, depending on your reaction to the initial dose.
There are some possible disadvantages of skin patches; local skin irritation including occasional blistering which occurs in about 20% of women and this can be very distressing.   
Again if a woman still has a uterus she must take progesterone. Micronized Progesterone is best and you should follow the instructions as per the manufacturer or your medical practitioner’s advice.

OESTROGEN GEL

       These are the latest preparations of oestrogens which are becoming popular although   they are expensive. These are also a transdermal preparation, as they go directly into the blood stream when applied to the skin. They come as gel, cream, mist pump and spray.

 INJECTABLE OESTROGENS

      Currently there are several other preparations, of Oestradiol Valerate.  They come in different intramuscular strengths. The injection can last from 2-6 weeks depending on the severity of oestrogen deficiency symptoms. It is very useful in postoperative days after the removal of both ovaries. It is also used when oral oestrogen should not be given. Recently it has been successfully used in some cases of premenstrual tension and postnatal depression.
The other injectable preparation is Conjugated Oestrogens; this is often used when there is intractable bleeding. Sometimes combined oestrogen and testosterone injections can be used in some circumstances especially if menopausal symptoms are difficult or if there is a marked loss of libido.

VAGINAL OESTROGEN AND OTHER PREPARATIONS

        Oestrogens are available as vaginal tablets and creams; and vaginal rings. Vaginal oestrogens are particularly useful if side effects are a problem with other forms of therapy or if only local treatment is necessary to improve the condition of the vagina and vulva.  Local Oestradiol inserts of 10 mcg produces effective relief of local atrophic vaginitis, dryness and burning without any significant side effects. The effect of vaginal cream is short-lived and is mainly local. A once daily dose does not affect the lining of the uterus and can be prescribed without progestogen. Other local vaginal oestrogens, are available in different parts of the world under different brand names.
The other vaginal preparations are:  Oestradiol vaginal ring which delivers 7.5mcg per 24 hours. It does not help with V.M .symptoms (like hot flush). Vaginal rings prepared from Oestradiol acetate are useful for women who do not have a uterus. It releases 50 -100mcg per 24 hours. It takes care of VM symptoms and Vaginal and Vulval health, for up to 3 months when a new ring is inserted. At present, vaginal rings, tablets and micronized vaginal progesterone if indicated is the treatment of choice from risk benefit point of view.

PROGESTROGENS
   This is the other female hormone which is important to be used with oestrogens when we use HRT. Unfortunately many different names are used for it interchangeably without attention which creates confusion for simplicity please remember progesterones are natural hormones and progestins are all synthetic. For simplicity just remember Progestogens. They have different brand names in different parts of the world. Progesterones are now available in many forms, oral, injectable, vaginal rings, combined with oestrogens. The best form of progesterone used now today is called Micronised Progesterone. It comes as oral and vaginal, under different names. This was first made in 1980. It is very well tolerated especially if used vaginally.  Do not use it if you are allergic to peanuts. The normal precautions to its use are such as DVT, liver problems. It does not interfere with the protective effect of Oestrogens on the heart. Progesterone Intrauterine devices (IUD) are also available which use another preparation of progesterone. If women having Oestrogens, or having too much bleeding, cannot tolerate progesterone, can have this IUD. This is also a contraceptive.
Medroxyprogesteronacetate (MPA) is the most recommended and popular form of progestogen. Research shows that it does not adversely affect blood lipids (cholesterol and triglycerides). It is available in 2.5 mg, 5 mg and 10mg tablets. Norethisterone is a progestin (a synthetic preparation) also commonly used. Now most commonly used preparation is Micronized Progesterone.
COMBINED OESTROGEN AND PROGESTERONE
  These are made by different preparations. They are normally used in contraceptive pills. These are also used in peri menopause to correct the early bleeding patterns and are also contraceptive. One such pill is a combination of oestradiol and a new progesterone called Dinogest which is very useful in peri menopause and bleeding problems and contraception is desired.
 TESTOSTERONE
    It is very useful when ovaries have been surgically removed; it helps with sex drive and fatigue. It is available as implants, creams, patches or gel.
TIBILONE
  Tibilone is a synthetic, steroid pill combining the actions of oestrogen, progesterone and testosterone in small doses with the advantage of not causing uterine bleeding if given to women whose menstrual period was over 12 months ago. It is used for HRT and Osteoporosis. It should not be used in women who have had breast cancer or stroke. It increases the risk of stroke. It benefits vagina, brain, bones, hot flashes, and endometriosis. It also protects the uterus, breast and liver from side effects. Even if you have a uterus you do not require progesterone because of its progestogenic action. Besides this it helps to have freer testosterone which improves sexual function. Side effects of Tibilone can be vaginal spotting, discharge, irritation, abdominal or breast pain and some unnatural facial hair. Generally it is a well tolerated HRT.
Personal story
Alcoholism and HRT
         Joan, 46 years, was suffering severely from menopausal symptoms, mainly hot flushes and irregular bleeding. She asked for help to cope with her personal, family and marital problems and her heavy drinking. Alcoholism had caused liver damage which meant she could not take oral oestrogens. Skin patches (75 g) were prescribed twice a week (75mcg/24 hours), plus 5 mg of progestogen daily, as continuous therapy.
         Joan was happy with this therapy which was tailored to her requirements after a few trials over four months. A balance was eventually reached between complete relief of her symptoms and the irregular uterine bleed. She then felt physically well and emotionally strong enough to cope with the family stress and her failing marriage.

Contraception and Menopause
         HRT is not a contraceptive pill. The best option is to continue your current method of contraception for the one or two initial years after menopause. If you are already on a contraceptive pill and a non-smoker you can continue. If you have an intrauterine contraceptive device, you may leave it in. Some women may already have had a (laparoscopic) sterlisation: the clipping of your tubes (in previous techniques, referred to as having your tubes tied). Currently there are newer Hormone progesterone intra uterine devices women can use with oral or transdermal oestrogens, which are very useful in some situations for menopausal symptoms, for double purpose of HRT, contraception and, in cases with excessive bleeding .You should discuss these variations with your doctor.
SERMS
         The other group of drugs as already mentioned used for management of menopause are called, Selective Oestrogen Receptor Modulators. These have different oestrogen like actions on different organs, like oestrogens on one organ and anti oestrogens on another. There are three such drugs commonly used. (1) Raloxifene, this is not an oestrogen however it acts like oestrogens, prevents and cures osteoporosis. It has an anti oestrogenic effect on breast cancer and uterus hence protects these organs. It does not help with V.M. symptoms; in fact it can make them worse.
(2) The other is a combination drug called Bazidoxifene, it is Bazedoxifene combined with conjugated equine Oestrogens. It protects the uterus and breasts when women take oestrogens for severe vasomotor problems. They then do not have to take progesterone saving its side effects.
(3) Ospemifene is another SERM, which is very favorable to the vagina. It is used as a daily single tablet for painful sexual activity. Main side effect is hot flushes and muscle spasms
Whenever a woman starts to take any treatment always read the enclosed information on the drug, the contraindications and side effects, if need be discuss it with your care giver.
Stopping HRT
         If for some reason, you have to stop taking HRT, it is better to do so gradually. While not addictive in any way, HRT is a very attractive addition to your body’s chemistry because it replaces your depleted naturally occurring hormones. If HRT treatment is stopped suddenly, then there may be some bleeding and a resurgence of the symptoms of menopause. It is the sudden drop in oestrogen levels which causes symptoms, rather than the actual oestrogen level.
Few years ago it was believed that HRT should be given in the smallest dosage for the shortest possible time, however this view is now superseded by saying it should be given in adequate dosage for adequate time.  These of course are individualized. If a woman is over 60 this should be carefully supervised. Generally this should be discontinued after 3-5 years, over age 60, any suggestion of DVT or STROKE, any signs of Heart disease or any other problems.
Alternative therapy for hot flushes
         Sedatives, tranquillizers and drugs used for treating migraine can offer some relief if you feel your menopausal symptoms are making your life intolerable and you are in the rare situation where HRT cannot be prescribed you may take these drugs.
The drugs used for treating migraine may sound unlikely but they some times 
seem to work by stopping severe vasodilatation (widening of the arteries) which accompanies a hot flush. The basic change both in migraines and hot flushes is vasodilatation, followed by vasoconstrictions.
A woman can help herself by changing her life style factors: exercise regularly, keep cool, yoga, stop smoking, eat properly, and do all the life style things, everybody keeps talking about. The most common alternative treatments offered for menopausal symptoms are evening primrose oil, ginseng, royal jelly, black cohosh, angelica St John’s Wort and vitamin E.
         The main constituents of evening primrose oil are the essential fatty acids, linolenic and gammalinolenic acids. Literature on evening primrose oil states that linolenic acid has an oestrogen like action. The truth remains that there is no well defined and constant formulation of evening primrose oil, ginseng or royal jelly. Their value is claimed for the treatment of premenstrual tension, atopic eczema, and diabetes and menopause symptoms. Hundreds of women claim benefit from these remedies and it is quite possible that they do receive some benefit. The difficulty is that preparations are not subject to the same regulatory requirements which control pharmaceutical drugs. St John’s Wort is known to cause side effects if used with others drugs. I have personally had a case where it caused oozing problem following a caesarean section, where the woman did not inform me that she was taking it during pregnancy.
BIOIDENTICAL OR NATURAL HORMONES
         These are prepared from plant sources and are supposed to be identical with human hormones, hence called natural.  They are regulated by the levels in the saliva; there is no proof to say that these are related. They have not been studied and the clinicians do not know if they are effective and free of side effects hence they are not advised. The other thing is that these are being balanced by the hormone levels in a woman’s saliva, but we do not know how they are related to the symptoms. There is also no solid evidence to suggest about their safety and effectiveness. Because of these reasons they are not recommended but still used all over the world.
ANTIDEPRESSANTS  AND OTHER MEASURES
         These are not licensed for treatment of menopausal symptoms, however most experts believe these are very useful when treatment for menopausal symptoms is required after breast cancer, when normal HRT cannot be used. There are two main types of these, called Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Noradrenaline Reuptake Inhibitors (SNIRs). There are many such compounds, let us just call them SSRIs and SNIRSs. They are very helpful. They also have side effects such as anxiety and dizziness but settle down over time.  Your care giver can discuss all this with you.
Other Treatments used for hot flush’s is an anti seizure drug called Gabapentin. It improves the quality of sleep but also causes sleepiness and fatigue. Clonidine is another mild drug women can take for hot flushes if she cannot take oestrogens. This is normally used to lower blood pressure. Stellate Ganglion Block (nerves in the neck) in some special clinics is given by specialists to help with hot flushes.There are many new drugs which are being used for management of Osteoporosis and Genitourinary Syndrome of menopause.
SPECIAL CASES AND MANAGEMENT OF MENOPAUSE
BREAST CANCER
         If it happens in younger women hot flushes are very bothersome. The drugs used for these cases are Antidepressants, SSRI, SNRI, Clonidine and Gabapentin and Stellate Ganglion Block.  Women will need to improve their life style factors and diet to have more help with hot flashes. There is no conclusive evidence on benign breast disease or uterine fibroids.
 ENDOMETRIAL CANCER
       It is highly unlikely to recur after 2 years, so HRT can be used after that time predominantly progesterone only drug. It helps with hot flushes and bone loss.
 LIVER CANCER AND BOWEL CANCER
     HRT has a protective effect and can be used in some forms of ovarian cancer as well. Consult your oncologist for all of these. Alzheimer is less frequent in women who are on HRT. In older women it is useful for Osteoporosis and Genito Urinary Syndrome of Menopause.
PREMATURE OVARIAN INSUFFICIENCY
       When a woman’s ovaries cease to function before the age of 40, it is referred as premature ovarian insufficiency. Generally if it occurs near the age of 40, it is often referred as premature menopause, however if it happens in a teen ager it can be very traumatic. It used to be called as ovarian failure; however the term insufficiency is preferred as it tends to have intermittent remissions. With reference to Menopause it is simple expect in some situations when a women has not yet achieved her child bearing. If she had normal periods until now it only means that is run out of her eggs.  If she has finished her child bearing, she can be advised and treated like any menopausal woman after confirming the diagnosis, advice about cardiovascular disease, osteoporosis and contraception. If there is desire to try for a child she can be referred to, have help from specialist on reproductive technologies, which are very skilled now. Recently they are even trying to use Stem cell techniques to produce new eggs, which we always thought could never happen.
A NEW DRUG
    This drug called MLE 4901 is currently being studied in London for Vasomotor   Symptoms of Menopause, by blocking a receptor in the brain called NKB, it is linked to hot flushes, lack of concentration, sleeping problems, weight gain and many other targets and works within 3 days. It is still being studied.
Key points
1.
Women should be as informed as much as possible about menopause and its symptoms. Long term problems such as, Osteoporosis, Cardiovascular Diseases and Gentourinary Syndrome these benefit with proper treatment. This is provided in full agreement to women. HRT or MRT is the best treatment.  The benefits are enormous as long as it is started soon after menopause or even in peri menopause if you have symptoms.
2.
It should be started soon after menopause within 6-10 years and under the age of 60.
3.
The side effects during HRT can also be due to aging rather than HRT alone.
4.
The studies that were conducted by WHI giving serious results due to HRT were due to a poor selection of women and their age group rather than HRT. They themselves have tried to revise their results.  They reported the risk of breast cancer as 25% how ever there is only 1 extra woman who gets breast cancer out of 1000, in one year.  Similarly if you take HRT in early years 50% less women die of heart attack in their older years and have fewer deaths due to osteoporotic fractures.
 5.
Recently many safer HRT’S and their relative drugs have been discovered which are safer, have less side effects, protective against breast cancer, stroke, heart attacks, osteoporotic fractures and genitor urinary syndrome of menopause.
6.
There are many different routes by which HRT can be delivered; better quality of oestrogens can be delivered as transdermal, gel, patches, implants, and injections. They protect the liver and are effective against the thromboembolic disorders.
7.
There are new antidepressants that can be used for treatment of vasomotor symptoms in women after breast cancer that cannot use HRT.
8. 
There is another group of drugs called SERMS which are useful for treatment of osteoporosis and genitourinary syndrome of menopause. Laser treatment is also being tried with caution for this.
9.
Side effects can be eliminated by adjusting the drugs, dose, and route of delivery.                         
10.
Although not addictive, HRT does cause withdrawal symptoms, mainly hot flushes. HRT should be stopped gradually to avoid these unpleasant symptoms.
11.
 Life style factors are important and should be taken care of, to make menopause happy and healthy.
 12.
New drugs and research is continuing to make this long period of women’s life happy, healthy and fulfilling.

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