PREMENSTRUAL SYNDROME

Premenstrual Syndrome (previously and even now called premenstrual tension) is one of the most common problems woman suffer soon after the menstrual cycle starts. Almost 50 to 95 % of women suffer from this condition in some form (may be very mild) some time in their life during their menstrual cycles. It is worst between the ages of 20 to 40, around peri menopausal time, and often in post natal time.

This does not happen during pregnancy as women have no periods during pregnancy. This is a series of symptoms that women suffer in the last week of their menstrual cycle (luteal phase). It lasts for about 7 -10days settling down soon after the menstruation (bleeding) starts. It has been cited resulting in poor studies, work performance, domestic life, criminal acts, life threatening, even suicide and murders.  When the problem becomes very severe, it is called premenstrual dysphoric disorder (PMDD). This happens in 3 -8% of those women who suffer premenstrual syndrome (PMS). Even in my own working life, I have witnessed many serious crimes, suicides and murders.

For a very long time medical specialists did not believe in this, they thought it was all in the women’s mind. Luckily for those who suffer from this terrible disability, it is now well recognised as a problem of women’s reproductive life.

  WHAT CAUSES IT?

We don’t exactly understand what causes it. It is probably the result of irregular hormone changes during the ovarian cycle (menstrual cycle). Withdrawal of oestrogens and progesterone in the second half of menstrual cycle, sensitivity to progesterone may also be the cause. The second major problem is thought to be cyclical ovarian activity and the effect of oestradiol and progesterone on the neurotransmitters in the brain. These  neurotransmitters, are called Serotonin, Gamma-aminobutricacid (GABA)are other important key factors .Vitamin B6  magnesium deficiency and hormones such as serotonin, endorphins, and prostaglandins also play an important role. It is possible that this is an exaggerated response of some organs in the body, such as the breasts, brain and joints to these various hormone changes their withdrawal or deficiency or excess. One of the reasons why researchers were not able to give it a diagnosis, as it has too many symptoms; some authors have enumerated as many as 150 different symptoms. How is the diagnosis made?  The most important is the history. The clinician should ask his/her patient about when it happens, and what happens. This should be documented in writing in relation to the menstrual cycles for at least 2-3 cycles. That will give the diagnosis. No tests are required unless there are any associated problems. Sometimes a haemoglobin and thyroid function and prolactin (other hormone) tests are also done .Rarely it may be required to exclude Bipolar disorders (PSYCHIATRIC DISORDER). If the symptoms are in peri menopausal years a FSH is done to exclude menopause

The problems of PMS, Postnatal depression and increased peri menopausal depression occur in the same individuals so it was thought that there may be a genetic predisposition. A gene on oestrogen receptor alpha is being implicated. A lot more research is required to substantiate this.

Symptoms of PMS

These are divided into two groups

1) Psychological and Behavioural

These are mainly mood swings irritability, lazy and tired, inadequate sleep, feeling anger for no reason, anxiety and loss of control. These symptoms can make life very difficult if you are a professional woman doing a ward round or a court case. Your cognitive ability can also suffer. Food cravings are also very real.

2) Besides these there many physical symptoms, of these very severe headache is the worst. You can have very tender breasts, back ache, skin rash, pimples or acne and fluid retention. This adds to the weight gain. 

How to manage PMS or its severe form PMDD

In milder cases or in fact in all the cases we should pay attention to life style factors. Regular exercise walks meditation, Pilates, good sleep, avoid stress, alcohol, caffeine, tobacco and eat a well balanced and proper diet; rich in green leafy vegetables, fruits, lentils and some modern super foods such as quinoa, flax seeds and chia seeds. Most of these and others are very rich in Omega 3 and 6 fatty acids and linolenic acid.  Premenstrual syndrome is a complex cluster of symptoms difficult to explain, it is possible that these dietary supplements rich in these acids alter the fatty metabolism and alters the tissue sensitivity to another hormone called Prolactin. Prolactin is not directly related to PMS, but when prolactin is high, symptoms of PMS are more intense in women with Bipolar disorders. Symptoms of bipolar disorder become intense in the premenstrual phase. A lot of research is being done on management of women with both PMS and Bipolar.

With a correct life style you can help your PMS as it reduces fluid retention, mood swings, and breast tenderness. Nibbling with healthy foods, e.g.: carrots celery and nuts, occasional dark chocolate, instead of commercial fried food and biscuits.

Complementary Treatments (CAMS) for PMS.

These CAMS are as ancient and as multiple as PMS symptoms.

Many of these are not licensed and proven to be of value, yet women swear by them. Celery seeds were very popular at one stage, as they cause diuresis which helped with bloated feeling, weight gain and to some extent breast tenderness. I never prescribed it, and never come across it being used in recent times.

Evening Primrose oil was used by many clinicians as well as other health professionals who recommended it. 1-2g of evening primrose oil was prescribed daily, either in the last two weeks of the menstrual cycle or continuously. It is still used today. It is generally useful particularly for very severe breast tenderness. It contains a chemical, gammalinolenic acid, which is required for production of prostaglandins in our body which in turn are necessary for many biological functions.

It comes as 1000 mg capsules, up to 2 capsules three times a day are recommended .Most recent research suggests that this is not used, unless breast problems are very severe.

Vitex Angus castus is another herbal remedy which is very popular. It is called by many different names. The tree is called a Chaste tree. Its extract (from fruits and leaves) is useful in the management of PMS, as it contains many chemicals such as flavinoids and iridoidglycosides.

It helps to regulate the bleeding and the menstrual cycle, tension, breast tenderness, and fluid retention. The dose is 1 tablet of 350 micrograms three times a day. The only problem with vitex is that it is difficult to find a standardised dose. 

The other herbal remedy often used is called St John’s Wort. It is useful for depression, cognitive and emotional problems. It is not to be used if you are already taking traditional medical drugs as it reacts with them. There are many other herbs recommended for PMS, such as lemon balm, turmeric and saffron. Please do not use them as their use is controversial and there are conflicting reports on them.

MEDICAL TREATMENTS OF PMS

Vitamin B6 this has been used for a long time for management of PMS. A dose of 50 mgms is given daily or in the second half of the menstrual cycle. Some clinicians use 100mgms but recent research suggest it is useless to use 100 mgms. There is very little evidence to show that it has more than marginal benefits.

Magnesium may have some benefit if used in dosage of 250 mgm per day. It can be tried for 2-3 months.

Calcium and Vitamin D

High doses of calcium have some benefit.  Try about 400mgms of calcium daily with 700 INU of vitamin D .When I was a child my mother was given an IV calcium injection with the start of PMS symptoms. This was very long time ago. From memory I think it helped her.

Spironolactone, these are potassium sparing diuretic that prevents your body from absorbing too much salt and prevents your potassium levels getting low, these help with bloating and breast tenderness. They have a limited use in PMS but are very useful in many other problems. It should not be used if you have kidney disease or high potassium. It is produced in our body by the Adrenal glands.

Danazol is a synthetic drug, its main use is for a condition called Endometriosis; I am sure most of you have heard this name as it is a very common female painful condition. This is not recommended for PMS, although it decreases GnRH hormone levels and theoretically may help. But it has two draw backs as it can cause masculization in women using it for long or if by any chance she gets pregnant it can cause masculization of the female foetus.

Women using all these remedies must remember about contraception.    

These were all marginal treatments. Let us talk about the definitive treatment of PMS and PMDD.

The real treatment is by suppressing the ovarian hormones. All oral contraceptive pills can be used, but the one which are most recommended are what we call third and fourth generation pills. This means that their quality has improved after every new type that has been invented. These are called  Yasmin or Yaz . These contain 20  micrograms  oestradiol and progesterone called drosperinone(30 mgm) for 24 days , instead of normal 21 days, thus the duration of PMS is reduced or it is hardly there; in spite of this it is recommended that this can be used as a continuous pill for 4 months, thus minimising the duration of PMS.  The main risk factor that remains is the risk of DVT. Be guided by previous history or family history before prescribing this pill or any pill. You have to make sure that a woman does not smoke, is under 35 years of age, and does not have any other risk factors such as blood pressure. Most of the pills are now very safe as regards DVT. As they contain newer, safer oestrogens and very safe progesterones and risk of DVT is negligible.

Oestrogen patches are very useful for treatment of PMS. In milder cases women are given oestrogen patches for 5-7 days when the symptoms generally start in varying strengths (25, 50, 75, 100mirograms) depending on the severity of symptoms. I have very good experience with these, they work well.

Oestradiol patches have also been studied. 100 micrograms of oestradiol was used twice weekly with cyclical progesterone. It was found to be useful. Progesterone is required for the protection of the lining of the uterus called the endometrium; if it is exposed to oestrogens for any length of time it thickens (Hypertrophy) and can cause bleeding and endometrial cancer. Progesterone should be used in the lowest possible dosage required. Your care giver will make sure if you have any reason why you should not be given oestrogens, such as history of breast cancer, DVT and blood pressure. Progesterone can be used as oral and intravaginal. This regime does not totally suppress ovulation so some other contraception will be required. I have a thought that an intrauterine Mirena can be used, and then progesterone will not be required. There is one problem with Mirena in itself, can cause low PMS like symptoms. The researchers have not done studies on the safety of this method (oestradiol patches with progesterone) as regards its effect on breast and endometrium. However in 20 years of their use of this method they did not find any adverse effects.  Come to think about it they were just trying to manipulate the normal menstrual cycle in the reproductive age group. Micronized progesterone orally or vaginally is very well tolerated. 100 to 200 mgms micronized progesterone is used for twelve days in each cycle. It can be used either orally or vaginally

Progesterone only drugs for PMS

These have been in use for a while mainly for contraception. These are depoprovera (250mgm) given every 12 wks by injection, etonorgestrel(implanon Nxt68mg) implanted in the arm under the skin lasts for 3 years, and progesterone only pills , the ones commonly used were called mini pills. Cerazette(Desogestrel) contains75 micrograms.they are given as one tablet daily These progesterone only contraceptives do suppress ovaries, but these tend to replace cyclical symptoms to continuous low grade PMS like symptoms. They also tend to cause irregular bleeding. 

GnRH or Gonadotrophic hormones recommended for treatment of PMS at present. They have been used for many years. They should be used in very severe cases or when the woman does not respond to other simpler treatments.  This is very expensive treatment and causes menopause like symptoms if used for, it can also causes the loss of bone density. The drugs used are called 1)Goserelin injection 3.6 mg four weekly. The other drug used is2) leuprolide acetate (lupron).As GnRH cause severe menopausal symptoms the women need HRT. The commonly used is called Tibilone (Livial) which is a synthetic steroid with oestradiol, progesterone and testosterone function. In case we use oestrogen progesterone women can have PMS like symptoms again. In cases on GnRH for more than I one year bone density should also be measured to exclude osteoporosis. These should be used only for short duration say 6 months, because of serious side effects. GnRH is also used for endometriosis, and shrinking the size of fibroids when they are large before surgical removal.

SELECTIVE SEOTONIN REPUPTAKE INHIBITORS (SSRI)

There is increasingly proven evidence that the chemical called serotonin is important in the causation of PMS and PMDD

Serotonin is a chemical messenger. It helps in many parts of our body particularly mood stabilizer, (HAPPY HORMONE), eating digestion healthy sleeping and the brain. In the brain it acts as a transmitter of messages in the nerve fibres and cells of the brain. “The neurotransmitters”. Serotonin deficiency causes depression and most of the symptoms of PMS and PMDD

It is found in the gut, brain and blood platelets. Many foods, such as eggs, cheese, milk, pineapple, tofu, salmon and kiwi fruit are rich in serotonin.  Exercise, sunshine and positive thoughts also help. SSRI are a class of drugs used for depression. We do not know how exactly they work but while transmitting messages they increase the level of serotonin where the message is to be transferred. It is used in cases of severe depression and PMS and PMDD. Women are happy to take it, as the regime of giving it for Pms or PMDD is different than given for severe depression. Drugs Escitalopram (LEXAPRO), Fluoxtine(PROZAC),and  Setraline(ZOLOFT) are commomly used. It is recommended that dose of 20mgms per day is given from 15 -28 days of the cycle. The benefit is immediate.  If the treatment is used only in the luteal phase of the menstrual cycle the dependence  to these drugs is unlikely. It is good to involve a psychiatrist in this treatment if a woman agrees

COGNATIVE BEHAVIOR THERAPY

This is a short psychotherapy which is oriented to change the perception, thinking feelings and behaviour of a woman which may be related to her personal problems.  This has been found useful, especially when used with SSRI’s.

SURGERY FOR SEVERE PMS AND PMDD

Surgery which is required or commonly done is a total hysterectomy and removal of both tubes and ovaries.

The removal of the ovaries is most important as they are the offending organ. It is best to do this after a trail of GnRH drugs and HRT so that you know that the woman can cope with this final treatment.  After this they only require Oestrogens, no progesterone is required as they 

have no uterus. HRT becomes very simple and free of most side effects as ESTRADIOL patches can be used. The strength of the patch can be guided by the intensity of a woman’s

symptoms.

SUMMARY

Although PMS and PMDD are known for more than 100 years, we do not clearly understand it.  In 1800 it was referred to as hysteria, like many other female disorders which the doctor did not understand.  It was Robert Frank who first described it as a hormone dependent disorder, but he was on the wrong track as he pointed out that it was due to excess of oestrogens. It took a female doctor to prove what it was. She (K Dalton) fought a murder case in 1953 and proved it to be due to PMS. Then she wrote an article in BMJ She said that such a large number of women do not have to suffer from  such a large number of physical and emotional symptoms each month for so many years of their lives . Modern medicine should help their misery.Thankfully it is being tackled now.  I think in one, sentence we can say it is a hormone dependent Depressive disorder, which creates a lot of misery for women. Alternatives’ to traditional help of diet, exercise, no alcohol, tobacco and good diet is showing some promise.

But a lot more work is required to prove that they are useful.  Some of these remedies are ANGUSCastes . Red clover (PROMENSIL) St John’s Wort.  Drugs used often such as diuretics. neurofen( NASIDS) progestogens should be replaced by newer generation of pills( YAZ ,YASMIN ). They are very effective and can be used continuously up to 4 months. The only problem is the minuscule risks of DVT. Please do not give it to a woman if there are any risk factors. SSRI are extremely useful and can be used for long time if only used in the second half of the menstrual cycle. GnRH is also excellent treatment, but it is expensive and HRT required for this is also expensive .Unfortunately it has long term serious side effects –osteoporosis. Hystrectomy and bilateral salpingo-oophrectomy is the last tool we have. It can be used in very severe cases with HRT.