Menopause

Posted On April 25, 2018 by Dr.Shobhana Mohandas

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Menopause is a term used to describe the permanent cessation of the primary functions of the human ovary. The ovary functions by releasing ova and hormones, both of which are stopped with menopause. Hormones produced by the ovary are oestrogen and progesterone. Both these hormones normally cause menstruation by their effect on the uterine lining, called the endometrium. Thus, when ovary sort of shuts down, with menopause, the effect of both these hormones cease.

Natural menopause occurs anywhere between ages of 45 and 55. Better nutrition may delay the onset of menopause. Menopause can be artificially induced if both ovaries are surgically removed. Rarely, menopause may occur at a young age, prematurely. It is surgically induced if both ovaries are removed for some reason.

 Natural menopause is associated with lack of functioning of ovaries, which are two hormone producing organs situated near the womb or the uterus. Normally, these ovaries produce 3 hormones,viz: oestrogen, progesterone and androgens. When they stop functioning, a woman faces many physical and mental changes

Menopause can have the following effects for a woman.

Irregular heavy bleeding: Before the actual cessation of periods, the periods may get delayed by 7 days or longer. Gradually a cycle may sometimes be missed and these periods of absence will finally lead to stoppage of menstruation. In some women, these changes may be accompanied by heavy bleeding. This requires medical help if it is very heavy, otherwise, she may become anaemic. Heavy bleeding also requires medical evaluation to rule out pathological causes of bleeding.

Hot flashes: The sudden sensation of extreme heat in the upper body, particularly the face, neck, and chest is referred to as a “hot flash.” Perspiration, flushing, chills, clamminess, anxiety, and occasionally palpitations can occur. They last anywhere between 1-5 minutes.

Osteoporosis: Osteoporosis literally means porous bones. Many years after menopause, the process of bone formation is not as fast as the process bone loss and this leads to less strong bones. In women, this is partly attributed to lack of the hormone oestrogen.

Loss of cardioprotection : It is known that women who have not undergone menopause have less chance of getting a heart attack as compared to men of the same age. However, once her ovaries stop functioning, the odds that a woman may get a heart attack are the same as for men of comparable age. The protection provided by oestrogen is no longer there.

Hypothyroidism as a consequence of menopause. There is reduced production of a hormone called thyroxine, normally produced by the thyroid gland , situated in the neck. The woman as a consequence, may tire easily, may get water logging in her body, and in extreme cases may not be able to tolerate cold.

Depression: Women in their menopausal period may suddenly develop depressive symptoms, like easy crying, easy irritability, or sleeplessness. These symptoms are caused in some women due to fluctuating oestrogen levels, which has secondary effects in the brain. Usually at this time, the woman also faces an “Empty nest syndrome”. This means, till about 40 years, her house was filled with echoes of her children asking her for something or screaming for something not done. But suddenly they leave her and fly away to be on their own. She suddenly feels unwanted and this negative feeling adds to her symptoms of depression. If it is severe, along with medicines to replace deficient hormones, she may need antidepressant medications.

Vaginal symptoms: Due to lack of the hormone oestrogen in late menopausal years, there is dryness in the vagina. There also can be itching and burning sensation. There may be small breaks in the vaginal skin in extreme cases. This can be treated with local oestrogen creams or tablets.

Hot flashes:

 Hot flushes are sudden or mild waves of heat on the upper part of the body that last from 30 seconds to a few minutes, caused by a decreased estrogen production during menopause. Hot flushes are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may last from two to ten minutes for each occurrence. The sensation of heat usually begins in the face or face and chest, although it may appear elsewhere such as the back of the neck, and it can spread throughout the whole body. In addition to being an internal sensation, the surface of the skin, especially on the face, becomes hot to the touch. The sensation of heat is often accompanied by visible reddening of the face.

In severe cases, Menopausal Hormone therapy is the only solution

Solutions available for hot flashes are as follows:

1. Estrogen only for women without uterus
2. Estrogen with progesterone for women with uterus to prevent endometrial hyperplasia
3. Tibolone for women with contraindication to estrogen or progesterone
4. SERMS.
5. Phytoestrogens
6. Clonidine, and other miscellaneous treatment options.

Oral oestrogen preparations:     The estrogens currently available in India are

1. Conjugated equine estrogen;strength: tablets of 0.625mg and 1.25mg.
2. Estradiol valerate                     strength: tablets of 1mg and 2mg.
3. Estriol                                         strength: 2mg tablet.

   Conjugated equine estrogen has been the most studied estrogen preparation.  It is the gold standard against which all other preparations are studied. Micronised estradiol valerate is a single estrogen preparation, as opposed to conjugated equine estrogen, which is a conjugate of different types of estrogen.   Estriol has been found to have less effect in causing breast cancer and has less uterine stimulatory effect,as it is a weaker estrogen.But estriol affords less cardioprotection compared to other estrogen preparations .It is required in very high doses(12mg) to effect prevention of osteoporosis by increasing bone mineral density and at such doses the side effects may be intolerable.

For treatment of hot flushes usually double dose of estrogen (1.25mg of conjugated estrogen or 2mg of estradiol) may be needed.   Treatment should be given on all days of the month as giving it for only 25 days has no added advantage and some women may develop symptoms during this week off. For the treatment of hot flushes treatment may be given for a year and stopped for a week to see if symptoms recur. If they do not recur treatment may be stopped. If they do recur, treatment may be continued for another year after which the patient may be re-evaluated.

    Estrogen in HRT can cause Nausea,dyspepsia,leg cramps,breast tenderness,vaginal discharge and withdrawal bleeds that may be unacceptable to the patient.  The breast tenderness and nausea may disappear in a few months. If the other side effects bother the patient, switching over to another estrogen preparation, reducing the dose, switching over to continuous combined therapy are other alternatives.

    Progestin supplements:

The only indication for adding progestin suppliments to oestrogen replacement is to avoid the complication of endometrial hyperplasia which might occur with oestrogen therapy alone. Hence progestin supplimentation need be given only to women with intact uterus.  Supplimentation with progestins has to be given at least 10 days per month to prevent endometrial hyperplasia.

 

There are two methods of supplimenting oestrogen therapy with progestins.

1) Cyclical therapy: Here the progestin therapy is given for 10-12 days every month.

  2) Continuous therapy: Progestins in lower dose is given every single day of the month.

The difference in the two regimens is that continuous therapy is less assossiated with monthly bleeding and may be more acceptable to the patient.Medroxy progesterone acetate in the strength of 2.5 mg is enough for this purpose. For women who have contraindications to the use of oestrogen therapy single therapy with progestins has   been tried.Progestins by themselves have been known to reduce hot flushes.

The progestins that are available are:

1. a)Norethisterone b) Medroxy progesterone c) Dydrogesterone d) Natural micronised progesterone.

 Norethisterone: 1.25mg/ day in cyclical therapy and 0.3-1.25mg /day for combined therapy.

Medroxy progesterone  10mg/day for cyclical therapy and 2.5-5mg/day for combined therapy.

Dydrogesterone: 10-20mg/day for cyclical therapy and 10mg /day for combined therapy.

Micronised progesterone: 200mg/day for cyclical therapy and 100mg/day for combined therapy.

Medroxy progesterone acetate is the drug most commonly prescribed for this purpose.

Dydrogesterone and micronised progesterone which have lesser side effects have equivalent effects on the endometrium and provide useful alternatives for women who experience side effects with medroxyprogesterone. Side effects of progestins include mood symptoms such as irritability and depression, breast tenderness, and bloating. Oestrogen increases the level of  High density lipoproprotein cholesterol, but this effect is nullified to some extent by synthetic progestins which are added to prevent endometrial hyperplasia. Dydrogesterone which has a structure closest to progesterone  and Micronised progesterone do not nullify this effect that much, thus maintaining the cardioprotective effect of oestrogen.  However the price of both these  compounds is much higher than medroxyprogesterone acetate and for the middle income group it may be prudent to start  on a less costly preparation and to switch over to costlier drugs only in case side effects tend to bother the patient enough to stop Hormone replacement therapy.

Tibolone:Tibolone  is a synthetic steroid  with estrogenic, and to a lesser extent,progestogenic and androgenic properties . In postmenopausal women, administration of tibolone reduces gonadotropin secretion  , improves climacteric complaints , and prevents the decline  (and even increases) bone mineral density  without inducing the recurrence of menstrual bleedings.It is known as a “bleed free” HRT and is thus expected to have better compliance. The cost of therapy is, however ,very high and thus its use may be limited to the affluent population only .The dose is 2.5mg once daily.

  SERMs:       SERMs are selective oestrogen receptor modulators. They are estrogen look alikes and act as agonists on some sites and antagonists on others.  The idea is to have the beneficial effects of HRT like prevention of osteoporosis, hot flushes etc without troublesome effects like endometrial hyperplasia.

Phytooestrogens:   Phytoestrogens are weak estrogens of plant origin. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids) and whole-grain cereals, seeds, and nuts (mainly ligands). High dietary intake of plant estrogens not only reduces the risk for breast cancer but has been linked to fewer menopausal symptoms.

Non estrogen treatments for menopausal symptoms:

Nonestrogen treatments include Steroids(Progestins,androgens),SERMs, Phytoestrogens,Nonsteroidal medications(Clonidine,lofexidine,antidopaminergic ompounds, Bellergal, Propranolol,Natural remedies( Gensing,Vitamin E, Cohash, Bee pollen) and  Life style/environmental modifications( avoidance of caffeine,layered clothing, exercise).

Natural nutritional supplements to alleviate menopausal symptoms:

     Vitamin E,d alpha-tocopherol 100-400 IU two times per day, citrus bioflavenoids with ascorbic acid 200 mg four to six times daily could help.  The patient should reduce refined carbohydrate, caffeine, and alcohol intake.  Soy protein, 50mg per day has been shown to decrease the intensity of hot flashes.  Significant amounts of phytoestrogens also are found in cashews, peanuts,oats, corn, wheat, apples and almonds.

Osteoporosis (FAQ’s)

What is osteoporosis?

Osteoporosis is the thinning of bone tissue and loss of bone density over time. In osteoporosis the bone mineral density (BMD) is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered. Osteoporosis occurs when there is an imbalance between new bone formation and old bone resorption. Two essential minerals for normal bone formation are calcium and phosphate. After menopause sets in, oestrogen levels fall , and this leads to osteoporosis. Decreased dietary intake of calcium lack of weight bearing exercise, also contribute to the setting in of osteoporosis.

What are the symptoms of osteoporosis?

Osteoporosis is a silent disease. It may not cause any symptoms till there are minute fractures called fragility fractures, which commonly occur in vertebra, rib, wrist, and hip. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility in the elderly. If there is loss of more than 1.5 inches then it means already there are micro-fractures in the spine. This hump is because of weak extensor muscles of the back along with very small fractures of the upper backbone which go unnoticed most of the time and are not diagnosed in more than one-third cases. This interferes with the quality of women’s life by causing chronic backache, decreased chest space resulting in respiratory problems and decreased abdominal space leading to poor digestion.

How can one prevent osteoporosis?

Doing weight bearing exercises for about half an hour per day after theage of 35 is a good way of keeping osteoporosis away. Taking calcium rich food like milk or milk products, green leafy vegetables, and legumes,can aslo prevent osteoporosis. Calcium excretion is enhanced with intake of tea or coffee and one should cut down on their consumption.

How is Osteoporosis diagnosed?

One need not wait till one gets physical symptoms to know if the bones are weak. Periodic testing of the bones with special tests like DEXA or ultrasound of the heel bone can detect if the bones are osteoporotic.  This exam is used to measure bone mineral density (BMD). It is most commonly performed using dual-energy x-ray absorptiometry (DXA or DEXA) or bone densitometry. The amount of x-rays absorbed by tissues and bone is measured by the DXA machine and correlates with bone mineral density.

What are the indications to treat osteoporosis with drugs?

Answer: 1. In women presenting with fragility fractures

2.Radiological diagnosis of incidental vertebral fracture or osteopenia

3.T score of <-2.5  at hip or spine on Dexa

4.with secondary causes of osteoporosis and high risk of fractures

5. In absence of DEXA, intervention is individualised understanding a cost benefit ratio.

What are the drugs available for treatement of osteoporosis?

There are two groups of drugs, drugs that prevent bone resorption, and drugs that help bone formation.

Drugs that prevent bone resorption:

Bisphosphonates: Alendronate(10mg once daiy orally or 70mg orally once weekly),

Ibandronate (2.5mg orally daily or 150mg orally once a month)

Risandronate( 5 mg orally once a day or-35 mg orally once a week or-75 mg orally on two consecutive days for a total of                                                                   two tablets each month or-150 mg orally once a month)

Zolendronic acid: 5mg IV once a year, followed by once in 2 years for prevention

Estrogens: Conjugated oestrogen or Estradiol, if osteoporosis is accompanied by hot flashes.

Calcitonin:

Selective estrogen-receptor modulators: Raloxifene, Bazedoxifene, Ospemifene.

Drugs that help bone formation:

Parathyroid hormone (PTH):

Strontium Ralenate

Calcitriol

Newer drugs: Denosumab.

 

Menopause management initially and along with drugs should also include life style management like right exercise and diet.

 

 

 

 

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