There are various treatment options available to women who have undergone POI

In general estrogen therapy is the main option recommended both for management of symptoms of estrogen deficiency and its long term effects.

Options of estrogen therapy

  • Hormone replacement therapy
  • Combined oral contraceptive pill

However a small proportion of women choose not to use estrogen therapy or it might be contraindicated with certain medical conditions.  Alternative therapies will be discussed at the end of this section.

 

Hormone Replacement Therapy

HRT

HRT is normally recommended until the average age of the natural menopause which in the UK is approximately 52 years of age. There is no evidence that HRT increases risk of breast cancer and cardiovascular disease over and above that found in women with a normally timed menopause for this age group (52 yrs.)

The regimens used will depend on whether you have undergone hysterectomy or not, whether you still have some ovarian activity or still have irregular periods and, if not, whether you would prefer to have a withdrawal bled monthly.

Spontaneous ovarian activity may recur in 5-10 % of women with the resulting fertility implications. Therefore a decision made about which HRT to use will depend on each individuals women’s circumstances and whether or not they need or wish to use contraception.

There are many different types of HRT preparations available, so it is possible to choose an HRT that works best for each individual . This can often involve trying out more than one type, as not everyone will find that the first HRT tried is the one that suits them best.

There are two hormones contained in Hormone Replacement Treatment: 

  • Estrogen – which is the hormone responsible relieving symptoms experienced and also for protection of the skeletal system cardiovascular system and cognitive function. It may originate form plant sources (estradiol) . It is different from the estrogen found in the contraceptive pill, which is of synthetic origin and is more powerful than natural estrogen.
  • Progestogens – which are given with estrogens .There are many varieties of progestogens but all have the same function which is to protect the womb lining from becoming thickened from stimulation with estrogen

There are three major types of HRT

  • Estrogen only HRT
    For women who have had their ovaries and womb removed by a hysterectomy. Because the role of progesterone is simply to protect the womb, this group of women do not need progesterone and are therefore usually prescribed estrogen only HRT
  • Cyclical HRT
    Cyclical HRT contains estrogen and a progestogen and this will produce regular bleeding. These are also sometimes referred to as sequential HRT. They are used for women who still have irregular periods or prefer to have a monthly bleed
  • Continuous combined HRT
    This contains similar hormones to cyclical HRT (estrogen and a progestogen) and is is used for women who do not want to experience a  bleed or have been bleed free for 2 years or more

Different preparations of HRT

As well as containing various combinations of different estrogen’s with or without progestogen’s, HRT is available in a range of forms, which are:

  • Tablets
  • Once or twice weekly Patch
  • Daily Gels
  • Implants

Tablets

HRT is most commonly prescribed in tablet form and there are many different brands available containing varying combinations of estrogen alone or in combination with progestogen.

Advantages:

  • Easy to take
  • Easy to stop
  • Discreet to carry
  • Easy to adjust dose

Disadvantages

  • Need to be taken daily

Patches

Skin patches deliver the hormones directly to the bloodstream through the skin. (transdermal)  and are changed once or twice a week. There are many brands available containing estrogen alone or in combination with progestogen .transdermal forms of estrogen which avoid first pass metabolism, have the advantage that they do increase clotting factors into the blood and reduce the small increase in risk of developing a deep vein thrombosis that occurs with oral medication

Advantages:

  • No need to take tablets
  • Easy to stop taking

Disadvantages:

  • May cause skin irritation
  • May be visible
  • May fall off
  • Need to remember when to change

Gels

Estrogen gel can be applied directly onto the skin to deliver the hormone into the bloodstream,again transdermal preparation and therefore avoid first pass metabolism and do not increase risk of deep vein thrombosis

Advantages:

  • Delivers estrogen direct to bloodstream
  • Easy to use and to stop

Disadvantages:

  • Can be messy
  • Need to apply correct amount

Implants

Small pellets of estrogen are inserted under the skin using a local anesthetic, they last for about six months delivering the hormone into the bloodstream. This is not first line treatment and usually used in patients post-hysterectomy when symptoms are not controlled by other means.

Advantages

  • Can forget about them once in place
  • Long-lasting

Disadvantages

  • Involves surgical procedure and local anesthetic
  • Not easy to reverse or stop
  • Levels of hormones in blood can be too high at first
  • Women with POI, may need to have a higher dose of estrogen to control symptoms.

Progestogens

For women in whom the uterus (womb) is present, a progestogen is added to the estrogen to reduce the risk of estrogen causing thickening, and possibly cancer of the endometrium (lining of the womb). Progestogens are mostly made from plant sources and resemble the naturally occurring progesterone, usually produced from the ovary in the second half of the menstrual cycle. The two main types of progestogen currently used in HRT are: those most closely resembling progesterone dydrogesterone, drospirenone medroxyprogesterone acetate and micronised progesterone, utrogestan and those derived from testosterone: norethisterone, norgestrel and levonorgestrel.

These are either combined with the estrogen as a patch or tablet or taken separately as a tablet

If side effects are experienced on one type of progestogen, changing the type or route of progestogen may help.

Mirena coil

This is a small device which fits inside the womb It can usually be fitted in an out-patient clinic with minimal discomfort, it releases a small amount of progestogen hormone to the womb lining, making it thinner and hence making heavy periods lighter. It is mainly used as a contraceptive but has many uses in gynecology . Mirena can be used to provide the progestogen part of HRT.

At first it can sometimes be associated with irregular spot bleeding, which can be irritating, but this nearly always settles.

With a Mirena in place, any form of estrogen can be used to control menopausal symptoms either tablet patch or gel.

Mirena is particularly helpful when there are heavy bleeds with sequential HRT, when contraception is still required along with HRT, or when there are side effects from the progestogen part of HRT.

Once inserted it remains in place for 4 years – the advantage is estrogen can be increased without needing to increase the dose of progestogen and it negates the need to take an extra table daily

What are the currently used first line HRT regimens?

Ideally estrogen delivered transdermally via a patch or gel.  These preparations are known as bioidentical hormones.

Estradiol patches

50 -200mcg changed 2x weekly

Estradiol gel 

Oestrogel 2-4 apps daily

Sandrena gel 0.5-2.0mg /day 
These are combined with Progesterone /progestogens.

Oral micronised porgesterone – utrogestan 100mg daily or 200mg between day 1-12 or mirena coil

Combined oral regime

The preferred oral preparations are:

Estradiol /dydrogesterone range

1:10 2:10

Conti 1.5

Conti low dose 0.5/2.5

Combined oral Contraceptive

All oral contraceptive pills contain ethinyloestradiol, a strong synthetic

estrogen designed to prevent ovulation, and so they have often been used as HRT in young women. Oral contraceptive pills are, however, stronger than natural estrogens and probably carry a higher risk of blood clotting (thrombosis) than occurs with estradiol valerate or conjugated estrogens.

Oral contraceptives provide estrogen for only three weeks in every four – the fourth week being ‘pill-free’. For women who are estrogen-deficient, the lack of estrogen during this pill-free week can cause symptoms and it seems more appropriate to provide estrogen continuously as with most forms of HRT. The Pill can be obtained free of prescription charges.

Psychologically for teenage girls the pill may be a more acceptable form of replacing estrogen as it doesn’t have the stigma that HRT may have. For women in their teens and early twenties, taking the Pill may make them feel more in touch with their peer group.

Vaginal dryness

Local estrogen’s such as tablets/pessaries and creams have shown to be a quick, effective and simple treatment for vaginal dryness.  These can be used safely in addition to systemic medication.

Within two weeks of treatment the majority of women have a significant improvement in symptoms

Local HRT is not used to treat hot flushes or prevent osteoporosis.

VAGINAL TABLETS /PESSARIES

Advantages

  • Simple to use and simple to stop
  • No mess when applying to vagina

Disadvantages

  • Suitable only for vaginal dryness

VAGINAL CREAMS

Advantages

  • Delivers estrogen direct to vagina
  • Easy to stop

Disadvantages

  • Can be messy to apply
  • Suitable only for vaginal dryness

Testosterone

 

Testosterone is one of the androgen hormones (predominantly male  hormones), which plays an important role in women’s health and wellbeing. In women, testosterone is mostly produced by the ovaries but it is also produced in other parts of the body. Androgens are important for muscle and bone strength and for the growth of normal body hair. Androgens may also have important positive effects on mood, wellbeing, energy and vitality in women.

After surgical removal of the ovaries, circulating testosterone levels drop by 50%. Levels may also be reduced in women after a hysterectomy with conservation of the ovaries; this is possibly because the blood supply to conserved ovaries may be affected by surgery.

Studies have indicated that testosterone treatment can improve mood and sense of wellbeing. Furthermore, the use of testosterone is associated with improvements in some aspects of female sexual function and is an option that some women may wish to consider.

Previously in the UK, testosterone could be given in implant form or patch. However, the patch has now been withdrawn and the implant is only currently available in some clinics that have been able to obtain a source from out with the UK. The implant involves the insertion of a pellet every 6 months under the skin using local anaesthesic.

Testosterone gel is sometimes used but is currently only licensed for use in men in the UK and would be used in a smaller dose for women only under specialist advice. At the moment it is usual to offer testosterone therapy only to women who are already using systemic estrogen treatment.

All are unlicensed for women there are no concerns with safety and efficacy data thus far

Products used are

Testim gel one pea sized amount applie to lower abomen daily – tube to lasts 10 days

Testogel gel one pea sized amount daily – tube to last 10days

Tostran  one pump every 2 -3 days

The aim of treatment is to bring women back to physiological range and provided these dosages are followed women should not experience serious reversible side effects such as increased facial hair or deepening voice.

It is essential that women undergoing testosterone treatment are supervised by practitioners with expertise in this area.

Non Hormonal prescribed medication

  • SSRI drugs (Selective Serotonin Reuptake Inhibitors).

This is a class of anti-depressant drugs which seem to work on the “thermostat” receptor as well as neurotransmitters. Examples are Venlafaxine, Fluoxetine, and Paroxetine. They have been studied and widely used effectively for reducing flushes in women who have had breast cancer. The dose of SSRIs can be started low and increased gradually to minimize side effects.

  • Gabapentin

Gabapentin, a drug which is used to treat epilepsy, migraine and nerve-related pain, has been shown to reduce flushes. It may be particularly beneficial for the symptoms of bone  aches, pains and paraesthesia. Possible side effects include dizziness, fatigue, tremor and weight gain but side effects can be reduced by starting at a low dose and increasing the dose gradually.

  • Clonidine

This is a prescription drug which can be used for migraine or high blood pressure and can also help a small proportion of women who suffer from hot flushes. The dose ranges from 2 to 3 25mcg tabs two times per day according to response. It is usually well tolerated but possible side effects include difficulty sleeping, dry mouth, dizziness, constipation and sedation.

 

Alternative therapies

       

The benefits of estrogen replacement are well known in the control of symptoms, and in the prevention and treatment of osteoporosis. However, some women do not take HRT, either because they are medically advised not to do so, have tried HRT and not tolerated it because of side effects, or prefer not to take it and take a more“natural” approach to managing POI.

For these women, alternatives to HRT can be helpful.

Alternatives are available as prescription or over the counter medications.

The use of alternative therapies is an expanding market and the choices for women can be often be confusing

Although they may be effective it is not an entirely a risk free approach and little information is available about the effectiveness of preparations. Try to ensure that the products you take are actually doing you some good and their planned effects are not overlapping.

General dietary and lifestyle measures in managing POI

Diet

Good nutrition is essential for everyone of all ages but especially in pateints with POI.

Eating a well balanced diet can help to reduce weight gain and minimise symptoms.

A healthy, well-balanced diet is also important in reducing the risk factors associated with heart disease and osteoporosis.

As part of a well-balanced diet: –

  • Eat three meals a day (i.e. do not skip meals)
  • Eat more fruit and vegetables – 5 portions per day
  • Avoid excess salt – limit in cooking and at the table
  • Avoid excess caffeine – limit tea, coffee and fizzy drinks
  • Cut down on fat and sugar
  • Do not overeat and limit “junk” or processed foods.

Exercise

Exercise is important for a healthy heart and cardiovascular system, maintaining strong, healthy bones, improving mood and in promoting overall well-being. Any exercise is better than none at all with weight bearing exercise being best in the prevention and treatment of osteoporosis e.g. brisk walking, jogging, dancing and aerobics. Swimming and cycling, although not weight bearing exercises, are good for maintaining joint flexibility and may also help to improve symptoms like flushes and sweats.

Rest and Relaxation

With increasingly busy lifestyles both at work and in the home it is important that time is made for adequate rest and relaxation. This is important in relieving stress and anxiety, improving mood and promoting overall well-being.

Excess stress is also linked to an increased risk of heart disease, and can worsen symptoms like flushes and sweats. It is therefore important to take time for yourself to relax with simple measures such as a soak in the bath or reading a book.

Smoking

Smoking  increases the risk of osteoporosis and heart disease, and can worsen symptoms like hot flushes and sweats. Women who smoke should therefore try to give up completely or cut down as much as possible.

Calcium and Vitamin D supplements

Calcium and Vitamin D are essential for strong bones and teeth. The best way of getting enough calcium is in the diet asit is more readily absorbed, however supplements can be beneficial to those women who have a low dietary intake through for example, not liking or not being able to tolerate dairy products, or having little exposure to sunlight. The recommended daily intake of calcium for women is 700mg, which is the equivalent of a pint of semi-skimmed milk.

Good dietary sources of calcium include dairy products, leafy green vegetables and oily fish.

Dietary sources of vitamin D include oily fish, margarine and eggs but our main source is from sunshine, with vitamin D being known as the “sunshine” vitamin. It may be worth considering a vitamin D supplement of 1000IU daily to maintain Vitamin D levels.

Over the Counter Alternatives

Phytoestrogens and Soya  are naturally occurring compounds with weak estrogen-like activity found in varying amounts in some plants. There is growing interest in phytoestrogens because there has been some evidence to suggest that women who come from countries who traditionally have diets rich in phytoestrogens, for example in Asia and Japan, experience fewer menopausal  symptoms and have a lower incidence of diseases like heart disease, osteoporosis, and cancers of the breast, womb and bowel. Although the evidence is encouraging and would suggest potential benefits for women in Western countries, further research is necessary. Phytoestrogens can be taken as a supplement or by increasing dietary intake, however quite radical changes to diet may be required to have an effect.

Foods, which are good sources of phytoestrogens, include: –

Cereals: oats, barley, rye, brown rice, couscous and bulger wheat.

Seeds: sunflower, sesame, pumpkin, poppy, and linseeds.

Pulses: soya beans and all soya based products.

Beans: chickpeas, kidney beans, haricot beans, broad beans, green split peas.

Vegetables: red onions, green beans, celery, sweet peppers, sage, garlic, broccoli, tomatoes and bean sprouts.

Soya, linseed oils and red clover are the richest sources of phytoestrogens.

Soya products like soya milk and yogurts are also richer sources and are available to buy in supermarkets. Phytoestrogens, such as Red Clover, are also available to buy in tablet form as an additional dietary supplement. They may, however not be suitable for all women.

Women who have had breast cancer or other hormone dependant tumours may not be advised to take these as it is uncertain whether or not even the tiniest amount of estrogen may have an adverse effect. More research is required.

Other Herbal Remedies

Black Cohosh

Relieves hot flushes, night sweats and vaginal dryness.

Evening Primrose Oil

Contains essential fatty acids. May benefit women who suffer from breast tenderness as a result of taking HRT.

Sage

Can relieve hot flushes and night sweats. Can be taken in the form of a tea.

St John’s Wort

Do not take this without consulting your doctor. Effective treatment for depression, sleep problems and anxiety.

Dong Quai

Often used for hot flushes.

Siberian Gingseng

Believed to increase estrogen levels, boost energy and vitality, and reduce anxiety and tension.

Chaste Tree

Also known as Agnus Castus this is a strong but slow acting herb, to be used with care. May be useful for hot flushes and mood swings.