LATEST ON HORMONE REPLACEMENT THERAPY(HRT or MHT)

After the publication of the women’s health initiative study and its publication in 2002, most women went off HRT which was detrimental to them. The truth is that HRT is very beneficial to women, the risk factors are small and can be minimised when given with due care and individualised. It should be given in adequate dosage (lowest dosage that helps) for adequate length of time as long as it is required. There is one prerequisite that is best for woman under the age of 60. After 60 they probably have already got the changes that we are trying to prevent. There are four conditions that are recommended for the use of HRT. 

1) Severe hot flashes, night sweating, mood swings

Forgetfulness, poor sleep, lack of concentration and fatigue. These put together make the quality of life very poor.

2) To prevent bone loss especially in delicate thin women with family history of osteoporosis. Recent researches suggested that woman of any age should be watched for and given treatment for osteoporosis when required.

3) Removal of ovaries or premature ovarian insufficiency (POI)

4) Genitourinary syndrome means sexual and urinary problems.

The fear that HRT causes cancer is over expressed. Recent studies suggest that HRT causes cancer in 1700 women per year, obesity will cause 1800 cancers per year, smoking causes 68000 cancers per year. You can see for yourself that the risk for cancer is small from HRT compared to many other life style factors. If 1000 Women start taking HRT at age 50 for 5 years 2 extra women will get breast cancer and 1 extra woman will get ovarian cancer. Although some: now generation, (Meaning studies over generations) studies suggest that the risk was underestimated. This research is still going on.

On the other hand HRT decreases the risk of bowel and stomach cancer.

Taking HRT is a very personal decision, and we clinicians have to be very careful in individualizing

a woman’s needs and involve her wholly in the decision making. The HRT is not given to women who have had breast cancer, or heart disease. In women with history of deep venous thrombosis,positive BRCA gene mutation, family history of breast cancer family history of deep venous thrombosis, we have to have detailed consultation and extra care when prescribing HRT to this group.

There are many types of HRT and given by many different routes and many different forms, we have come a long way since the WHI study was done using only conjugated combined oestrogens and synthetic progesterone which was called medroxyprogesteron acetate. This is a synthetically produced hormone. In the WHI, study there was no classification of age group, or symptomatology , all women between the ages of 50 – 79 were  included.

There are many such synthetic hormones, they are called progestin, and the progesterone obtained from plant sources is similar to human hormone and is called bioidentical. These progestins had upset the whole WHI study. These progestins had some different actions as well. They could potentiate the proliferative activity of oestrogens. Many research papers have been published since, in which natural progesterone and micronized progesterone are used, and they are given in a cyclic manner, as well as continuously. These studies do not show any effect on breast cancer risk.

Beside the breast cancer risk the other risks are: deep venous thrombosis (DVT), pulmonary embolism (PE), stroke, and endometrial cancer. It has no effect on primary or secondary prevention of heart disease. Any increased incidence in heart disease cannot be excluded at this stage. Some research papers have concluded that women on HRT have a longer life expectancy. This could be due to cardiac benefits. Many methods are being used to cut the risk of DVT. One such method is to use Tran’s dermal patches (On the skin). This sends the oestrogens directly into the blood stream without going to the liver; it is in the liver that coagulation factors are altered increasing the risk of DVT and PE.

There is another new group of drugs called SERMS. They are selective oestrogen receptor modulators meaning that at one organ they will act as oestrogens and at another organ they will protect it from oestrogens. We will talk about these as we go along.  They are very useful in full filling a woman’s need for HRT.

First reason why women need HRT is vasomotor symptoms (VMS). This includes hot flashes, sweating at night, poor sleep, forgetfulness, emotional changes, headaches, memory loss and fatigue. There are many more and; the more women you see, the more problems you will hear. If a woman is younger and not fully menopausal, meaning that she has not had a full 12 months without a period (which is what is considered Menopause), we call it peri menopause or menopause transition. During this period, many women have irregular and/or heavy periods.

Keep your investigation to a minimum. You may do a full blood examination, Thyroid function test, an ultrasound to exclude uterine and ovarian pathology. Thyroid disorders often occur at the time of menopause. Do a general examination including blood pressure; take a detailed personal and family history of breast cancer, DVT, heart disease or any other significant illness. Also make sure if she still has a uterus. HRT without a uterus becomes very easy. We need two hormones, Oestrogen and progesterone if the uterus is present, progesterone is to protect the uterine lining the endometrium, against endometrial cancer. In 1960 when HRT was started it was only oestrogens. Then there was a flurry of endometrial cancer, and then progesterone was created and added to HRT. In fact when endometrium is well protected the incidence of endometrial cancer is less in women on HRT as compared to the normal population. If a woman is peri menopausal and is having bleeding episodes in my view an intrauterine device called Mirena is very useful. You can read about this on my previous post on contraceptive and AUB. It is a small T shaped plastic device which contains a hormone called Levonorgestrel, it is placed inside the uterine cavity. It lasts up to 5 years, stops bleeding and periods after the initial hitch, it is a contraceptive and has no side effects in most women. There is no increased risk of DVT, stroke, heart attack and, breast cancer. Its use is tremendous when women are allergic to progesterone, and have risks from the above mentioned conditions, history of abortions and ectopic pregnancy, bone metabolic disease and high blood pressure. Imagine the cost saving instead of buying progesterone month after month. Only oestrogens can be used if you have no uterus except if you have suffered endometriosis. Oestrogen alone can restart the activity of a small endometrial patch lying in the abdominal cavity .This may have been inadvertently left while trying to remove deep infiltrating Endo. In fact endometrial cancer has been reported in these instances.

The other alternative can be oestrogen with a drug called Bazedoxifene, this is a SERM as explained, and it prevents endometrial cancer. The combination of Oestrogen with Bazedoxifene is also called Tissue Selective Oestrogen Complex (TSEC) this is a very useful drug in the management of HRT.

Micronized progesterone is another very useful hormone. It is identical to the hormone produced in a woman’s body by the corpus Luteum (develops in the ovary after ovulation).  Micronized progesterone can be used alone as a 300mgm tablet taken daily without estrogens, for hot flashes; It helps with sleep, forgetfulness and other vasomotor symptoms of menopause. It is best to take it at night, as it can make you drowsy. It can be taken as long as required. It is also given with oestrogens in a cyclic manner, 200mgm tablets daily for first 15 days of the cycle, 100mgm tablets daily for 25 days.

In spite of all these new drugs such as, Serms and micronized progesterone, HRT should be used for specific symptoms not in asymptomatic women of an older age group above 60. The age group between 45 -60 is expressed as window of opportunity and HRT should be started in this age group. If started after 60 it can do more harm than good as they may already have the changes we are trying to prevent. It cannot help to prevent secondary heart disease, if started at time of window of opportunity; it can still show improvement in cardiac, and brain function activity.

Most women require oestrogens and progesterone for protection of endomertrial lining. This can be given in a cyclical manner or continuously (cyclical progesterone will cause regular bleeding). It will depend on the woman’s wish, her age and how long she has been menopausal. If she is peri menopausal some forms of oral contraceptive pills are better. If she is well into menopause, a synthetic preparation called Tibolone, which acts both as oestrogen progesterone and even testosterone is good. It is   also useful after a hysterectomy with removal of the ovaries, or premature ovarian failure (POI, premature ovarian insufficiency). Women often require testosterone. Often in these women we put an oestrogen implant in (a little pellet under the skin it comes in 25, 50 75, 100 micrograms, we used a testosterone implant as well at the same time) It worked well. Start with lower dosage so that they do not get the side effects of a very high oestrogen dose, tender breast, nausea vomiting. In some countries Androgen preparations are available, which are useful for poor libido and energy level.

It is best to use Trans dermal oestrogens when you are using testosterone cream, as oral oestrogens interfere with testosterone activity.

Besides vasomotor symptoms and depression and osteoporosis, genitourinary problems which start happening with menopause to women are very nerve wrecking. On one hand you lose bladder control, on the other your sexual function goes all hey wire. You lose your libido, you have pain when you make love, and your vagina is constantly pain full. Systemic HRT oral or Trans dermal helps to some extant but still problems remain. Pelvic floor exercises are helpful for stress incontinence but psychosexual problems like dyspareunia remain. For this you can use moisturisers, they help to some extent. Local oestrogen creams and tablets are useful. They are made from the mildest form of oestrogens called oestriol, their absorption in the body is negligible hence you do not need any progesterone. The latest drugs for dyspareunia, is a SERM. This SERM is an oral tablet called Ospemifene. You require 60 mg dose orally daily with food. It is the latest non hormonal selective oestrogen receptor (SERM). We can only imagine how a woman with breast cancer treatment; suffers after all the treatment for her cancer. Her quality of life is totally destroyed. Ospemifene is a great drug for dyspareunia, along with moistures. So far it has not been found to have any endometrial or breast related concerns. Recent animal studies suggest that it may be as effective as Tamoxifan against breast cancer, further research is ongoing. The things that you can do, is look at your life style factors.  You have to have a good diet, exercise, yoga, aerobics, swimming, no cigarettes, very limited alcohol, less caffeine and try and cut down stress. Masturbation helps, try and dilate the vagina with a lubricated finger or dilator. You can use olive or coconut oil, this will break down adhesions. Try and have frequent intercourse whenever possible after foreplay. The relief of other symptoms such as VVS after breast cancer at this stage is very limited.  May be, as we discover more SERMS, treatment will improve. Complementary therapies are not recommended as we do not have significant results on their benefits and the way they are tested in the saliva is also not satisfactory.  You can try Acupuncture. There are some pharmacological preparations which are sometimes used. One of these is called Clonidine. Normally it is used for high blood pressure however if a woman has high blood pressure along with the other symptoms you can try this drug. It is not so popular any more.

Recently a group of drugs called selective serotonin and adrenaline reuptake inhibitors are being used. Normally these drugs are used for depression. Another drug called Gabapentin (Initially used for epilepsy) is also found to have meaningful help with VMS in women after breast cancer. The other drugs are Paroxetine and Desvenlafaxine. These drugs are still being worked out and for example, if a woman suffers from migraine, Gabapantin would be good, if a mood change is there, an antidepressant would be good. Do not use Paraoxitine if a woman is on Tamoxifan for breast cancer.  These drugs are still being worked out in relation to their risk benefit ratio. They have side effects such as dizziness, suppression of libido. Your clinician will be able to discuss these drugs with you in consultation with your oncologist. A few new treatments such as, called Stellate Ganglion Block, Surgical Improvements, and Laser Treatments are being tried for VMS and GSM. It is not recommended to try herbal treatments or progesterone cream as this is made with many steroids in the laboratory and can be harmful to women after breast cancer treatment.

These women should be supervised for osteoporosis and treated when ever required.

Prevention of bone loss also needs attention. Indication for prevention of bone loss particularly in women at high risk, and these are women with fair hair, low BMI, those who have used cortisone treatment for long term conditions, such as asthma, who have a family history of osteoporosis, sports women and premature menopause. The test required to assess the bone health is called Dexascan. Menopause hormone treatment (MHT) can be used as a primary treatment for bone specific medications, depending on who is treating the woman. The scenario of window of opportunity should be followed. Life style factors are important to follow.

The other very important group of women is women who have very low natural oestrogens.  This can be genetic ovarian failure, premature ovarian insufficiency, and premature surgical menopause. This group of women need MHT like any others if there are no contraindications of MHT until the normal age of menopause. They require much higher doses of MHT as they are younger. Please do not be hesitant to take higher doses as required and recommended by your clinician, if you had your own ovaries you would have been exposed too much higher dosages of oestrogens from your ovaries.  These women often require testosterone as well.

Let us now talk about the risk factors for HRT which is now often called MHT.

Current research shows that MHT should be started during the window of opportunity; that is between the ages of 50-60, within 10 years of menopause.  If started later, women have already undergone the changes we are trying to prevent. It is not helpful for secondary prevention of heart disease. Other safety issues are history of liver and gall bladder disease, previous breast cancer, endometrial cancer, coronary heart disease, unexplained vaginal bleeding, personal and family history of VTE, in this situation it is worth while investigating for any bleeding disorders. The other conditions are; Porphyria Cutanea Tarda( this is an enzyme disorder), high triglycerides, endometriosis , stroke, dementia, migraines and fibroids.

MHT can cause many side effects. They can be improved by adjusting the dose, and route of administration. It is now considered that the best route is patches, jelly, cream, implants and even vaginal. When used percutaneous or ( non orally) the drugs go directly into the blood stream without going through the liver ( which is called the first pass), thus protecting bleeding  clotting factors minimizing the risks of VTE, STROKE, and CVS problems. The common side effects of MHT are nausea, bloating, fluid retention, mood swings and tender breasts. In spite of the popular belief MHT causses weight gain it does not do so. Serious side effects are breast cancer, stroke, and endometrial cancer if oestrogen is not properly covered by progesterone, VTE, issues of bile production, in spite of the protective effect of oestrogens on heart, it can cause a Myocardial Infarction (Heart Attack). It depends on the age of the woman, obesity, smoking, her previous health and when MHT was started.

How long can women take MHT? There is no strict rule. 71/2 years is generally recommended as the symptoms generally last for 8 years and the risk of breast cancer sets in about this time. If a woman is happy and healthy they can continue to take it. Have a regular check up once a year. And if they have osteoporosis they need to have a biannual bone density test. I have had many women who have had MHT for 30-40 years. If they have no uterus, it is very easy to give them low dose transdermal patches once or twice a week, as oestrogen alone decreases the risk of breast cancer. Even if they have a uterus they can combine it with micronized progesterone as this does not increase the risk of breast cancer. Tibolone is another MHT (It is a synthetic drug) which exerts different actions on different tissues, it has oestrogenic effects on bone and vaginal tissues, progesterone like action on the endometrium, it has inhibitory activity on enzymes in the breast tissue. It provides relief from VMS and prevention of bone loss. It does not show any stimulation of the endometrium and breast tissue. It has some androgenic activity as well. It improves libido, improves vaginal dryness and decreases dyspareunia. Works all round. Most of menopausal women remain very happy with this. You need one table daily, which is a bit expensive, but what is cost for improved quality of life. Some of the side effects of Tibolone are thrush, increased hair, minor bleeding, talk to your clinician if they continue. If you are going to have an operation tell your doctor that you are on Tibolone.

  

BENEFITS of MHT (HRT)

18 of October 2016 was declared World Menopause Day, when it was found that around the world only 3% of women were aware of menopause and it’s problems. The purpose is to inform the world what can be done for effects of menopause. In 1998 there were 477 million, post menopausal women in the world, it is estimated that by 2025 there will be 1.1 billion postmenopausal women, who may suffer from different ailments of menopause, a poor quality of life. Surely it is our moral duty to come to the aid of these women. Let us see how we can help them. What are the benefits of HRT? First of all let us make them aware that they have to get in touch with a clinician, when they are still young and energetic, this is between the ages of 50 -60 years and when the symptoms of menopause start. Let us make them aware of these symptoms, the short term and long term health issues, benefits of MHT which can control a women’s irregular bleeding, hot flashes, sweating, lack of proper sleep and forgetfulness. This improves the quality of life .With increasing equality in men and women, many of these women may be CEO’s, school principals, senior doctors, lawyers and in many important positions and will greatly improve their life by these changes. Benefits of MHT (HRT) far outweigh the risk of MHT in symptomatic woman, if started during the window of opportunity i.e. within 10 years of menopause under the age of 60. It is beneficial if the MHT is individualised depending on a woman’s need and personal history. MHT with oestrogens alone is more favourable, than with both oestrogen and progesterone. So if she does not need progesterone do not give it to her,(Post Hysterectomy) or even if she needs progesterone she can use micronized progesterone which is very safe; both as regards breast cancer and DVT. If this particular woman suffers from irregular bleeding, without any uterine pathology, and also desires contraception, Mirena and an intrauterine device would be an excellent choice.

If the clinician chooses, an appropriate preparation and dose, adjustments as required and correct route of administration of MHT is very beneficial without any significant side effects.

Osteoporosis is a very big global problem. 30 -50 % of post menopausal women suffer from osteoporosis, which literally means bones with holes. This obviously makes them break easily; it causes fractures of the spine, hip and radius bone in the forearm with the slightest trauma. Besides the financial burden, the health professionals’ have to cope with woman with disability and pain and depression. You may not die of HRT but your chances of dying after an osteoporotic hip fracture are very high. There are 200 million women, worldwide suffering from osteoporosis which is increasing every day. It can be easily prevented by many different MHT’s without too many risks. Why not do it? In my view this would be the biggest benefit of MHT. In young women without a uterus we can give the oestrogens only or Tibolone. This is also very useful in women who had their last period 12 months ago. It is a synthetic preparation which has a selective oestrogen regulatory activity. It acts like an oestrogen and helps with VMS; it is protective on the endometrium and colon cancer. It has no risk of VTE many recent studies have shown no risk of stroke, as long as the women are under 60 years of age. It cannot be given to women who have had breast cancer. It has been shown than half the normal dose of Tibolone (1.25 mgmdaily), showed antifracture activity, improved BMD and bone turnover effects. We now have very good Dexascan to study BMD. The other MHT that can be used for Osteoperosis , is a combination of oestrogens( an another new SERM  Bazedoxifene . The combination of these two drugs is called tissue selective oestrogen complex (TSEC).

Incidentally this also helps with, management of menopause, VMS and genitourinary syndrome of menopause, improves libido, and improves vaginal tissues. This can be further helped by oestriol cream which is a very low dose cream, it is not absorbed in the body. This is further helped by testosterone preparations and the latest SERM Ospemifene. When a woman is not so depressed, sexually satisfied, not moody, no aches and pain, healthy skin with 25 % increase in collagen, less or no wrinkles, she is a much better woman to live with.

This has been used for management of menopause in women who still have a uterus and cannot use progesterone. This should not we used for women who have unexplained vaginal bleeding ,endometrial hyperplasia, DVT Thromboembolic disease, myocardial infarction, ischemic stroke, breast cancer,  oestrogen dependent cancers ,liver and kidney problems.

So we can see there are many types of MHT which are very useful for different problems in different women.

Provided it is stared soon after menopause (or within 10 years) between the ages of 50-60. The newer drugs and equipment helps a lot. Use purified oestrogens, micronized progesterone, SERMS (Bazedoxifene, Tsec, Ospemifene) SSRI,

Tibolone, Non oral hormone drugs.

All these drugs help our QOL, prevent heart attacks if started early, urogenital problems, reduced risk of colorectal cancer, Alzheimer’s, some help for a woman after breast cancer treatment, reduced risk of breast cancer ,and DVT.

Not useful for primary or secondary heart disease or prevention of diseases of old age.

Conclusion: HRT was initiated in 1936 when Robert Wilson published a book called "Feminine forever".  His concept was rubbished as he said all women need oestrogens and sexuality and sex were confused. When in the 80’s and 90’s I practiced as gynaecologist and suffering myself after an early surgical menopause, I realised how important it was to understand menopause.   I researched the subject and published a book in 1994 ( Menopause and Beyond), this was very well received by thousands of woman and now in 2017 I find that many women still suffer in silence, use unauthorised preparations because of fear. I am very glad that international menopause society has declared an international menopause day. This is doing a great job of publicity, information on life style factors to make the life of a woman after menopause to be healthy and happy. Life style factors are very important such as exercise, diet, maintain correct weight and help with the prevention of diseases such as osteoporosis, heart disease and genitourinary problems. This all has to start even before menopause (peri menopause or menopause transition). It is too late if you leave it for years, when it starts to show its ugly side. To help yourself if you need MHT OR HRT so be it, do not be frightened. Please talk to clinicians who are well informed about Menopause. In this day and age, they have very safe MHTs and there are very individualised treatment options with very little risk of DVTS and cancers. 

Please ask for help, do not suffer in silence make your life happy and healthy.