How do medical treatments for heavy periods work?

How do medical treatments for heavy periods work?

A:Combined oral contraceptive Pill.

During the first 14 days of a natural menstrual cycle, the lining of the womb (endometrium) is stimulated by oestrogen alone. Under the influence of the oestrogen the endometrium becomes thicker (proliferates Figure 2.3). Following the release of the egg (ovum ovulation), about 14 days before the next period is due, the endometrium comes under the influence of progesterone as well as oestrogen. The combined oral contraceptive pills contain combinations of oestrogen and progestogen (Q16.1). Each pill contains both hormones. They are usually taken cyclically for 21 days with a 7-day gap. One of the effects of the progestogen is to keep the lining of the uterus thin so that in the event that an egg is fertilised, the lining of womb cannot allow implantation, thus preventing pregnancy. As the endometrium is relatively thin and underactive, the monthly withdrawal bleeds tend to be lighter.

B: Progestogens

The standard textbook recommendation is that progestogens should be taken in the second half of the menstrual cycle e.g. From day 16 to 26. The logic behind administering the progestogen in the second half of the cycle seems to be that in the natural cycle this is the time that the ovaries are releasing progesterone. When young teenage girls or peri-menopausal women are troubled by heavy periods, cyclical progestogens taken in the second half of the menstrual cycle may confer benefit. In these situations, there is often evidence of anovulation (eggs are not being released) so that there may be oestrogen but no cyclical release of progesterone.

The majority of women with heavy periods, however, are ovulating indicating that their progesterone levels are normal. Most of the evidence would suggest that progestogens given in the second half of the cycle do not reduce blood loss. There have been suggestions that progestogens, may reduce period loss when they are given much earlier in the cycle, perhaps from day 5 to day 26. This would be compatible with the twenty-one day course of progestogen given in the combined oral contraceptive pill. It should be noted that the progestogen alone does not provide contraception.

If there is any likelihood of pregnancy occurring, dydrogesterone (Duphaston - Solvay) tends to be my first recommendation: Duphaston is licensed for use in pregnancy for women who recurrently miscarry. There is some reassuring data that medroxyprogesterone (Provera Pharmacia and Upjohn) has no detrimental effect on a fetus. Norethisterone (Primolut N Schering; Utovlan - Searle) could cause problems (masculinisation) to a female fetus, although this is not a problem in the early weeks of pregnancy. Nevertheless, before administering norethisterone, one would wish to emphasise the particular need for contraception.

C:Tranexamic Acid(Cyklokapron Pharmacia and Upjohn).

During each period, the blood lost from the vessels within the womb should clot (coagulate). As with a cut or a graze, the clot tends to stop the bleeding. Fibrin is an essential part of the blood clot. Fibrinolysins (lysis Greek, a loosening) in the cavity of the womb break down the clot so that the period loss is normally fluid. Tranexamic acid reduces this fibrinolytic activity so that the tiny blood clots sealing the bleeding vessels can continue to function for longer thus reducing the period blood loss. There is no reason to withhold tranexamic acid before investigation such as hysteroscopy and D and C. Two or three tablets three or four times daily as and when required would be the recommended dose. Tranexamic acid should not be taken if you have a history of thrombosis (a blood clot surgery risks).

D: Mefenamic Acid and other prostaglandin synthetase inhibitors - non-steroidal anti-inflammatory agents (NSAIs).

Prostaglandins are a group of hormones that have a variety of functions. They derive their name from the prostate gland (a gland of the male reproductive tract) although they are produced in other tissues including the endometrium. Endometrial concentration of prostaglandins is increased in association with menorrhagia. Prostaglandin synthetase is an enzyme (a chemical that acts as a catalyst promoter of a chemical reaction) that is crucial to the production of prostaglandins.

Prostaglandin synthetase inhibitors, also called 'non-steroidal anti-inflammatory agents', have a variety of valuable therapeutic uses. These include treatment of pain in general and arthritis in particular. Most of the research in relation to menorrhagia relates to mefenamic acid (Ponstan) although there are others in this group, including naprosyn, ibuprofen, indomethacin and diclofenac that may also prove effective. Mefenamic acid has been shown to reduce menstrual blood loss significantly. It tends to be of particular value when treating a combination of menorrhagia and dysmenorrhoea (painful periods). NSAIs are not recommended if you have a history of peptic ulcers or asthma.

E: Gonadotrophic Releasing Hormone Agonists.

Gonadotrophin Releasing Hormone (GnRH) is released by the hypothalamus and results in release of the gonadotrophins, FSH and LH, which in turn stimulate ovarian follicular development (Figure 2.6). Gonadotrophic releasing hormone agonists are used to block GnRH production in a variety of gynaecological situations. They can be used to stop the menstrual cycle and thus stop periods.

Figure 2.6

As oestrogen levels fall, menopausal symptoms (Chapter26) are common. Prolonged suppression of ovarian function will lead to osteoporosis (weakened bonesQ 26.24) and disease of the arteries. GnRHs can be used for a maximum of six months by themselves. They are extremely valuable in preparation for removal of fibroids (Q 23.17) and occasional situations such as stopping periods in patients with severe menorrhagia when blood transfusion is not an option (e.g. Jehovah's Witnesses). GnRH can be used in combination with HRT (add-back therapy) for longer than six months. GnRH treatment is extremely expensive precluding its prolonged use except in extreme situations.

F: Hormone Replacement Therapy (

HRT)

Menorrhagia beyond the age of forty years should be investigated (Q 24.9). Frequently women presenting with menopausal symptoms and menorrhagia, report reduced menstrual flow after cyclical HRT has been commenced. The menstrual cycles before the menopause are often anovulatory (eggs are not released). There is, therefore, progesterone deficiency in the second half of the cycles and the progestogens in the cyclical HRT would account for the improvement in the periods.

G: Danazol

Danazol (Danol Sanofi Winthrop) seems to be active in a number of areas of the reproductive system. It has some gonadotrophin inhibitory activity. It may also have a direct action on the endometrium. At higher dosage levels, it frequently induces side-effects particularly sickness. At lower dosage, such as 100mg daily, side-effects are less common and yet heavy menstrual flow may be reduced.

H: Gestrinone

This agent seems to have similar modes of action to danazol. It is longer acting and a typical dose would be 2.5mg twice weekly.

I: Ethamsylate.

This drug seems to increase capillary wall strength, increase platelet stickiness and reduce some of the adverse effects of prostaglandins (Q 24.17D). There is less convincing evidence of benefit with heavy periods.

J: Antibiotics.

Clearly when there is evidence of pelvic inflammatory disease (Q 20.2) antibiotics are likely to be beneficial. It is possible that there may at times be sub-clinical bacteria within the uterus (bacteria endometrialis) that may account for some otherwise unexplained menstrual disturbance.

A 34 year old lady had been investigated for intermenstrual bleeding and a polyp was removed. She presented again two years later as her periods had become extremely heavy on the first day for nearly a year. Clinical and ultrasound examination showed no obvious abnormality. Tranexamic acid (Q 26.16:C) to be taken during heavy loss and a course of erythromycin and metronidazole (antibiotics) were prescribed. She returned for review three months later. The tranexamic acid had not been required as her periods had returned to normal following the course of antibiotics.

There is evidence that intrauterine infection may be associated with bleeding between periods that may respond to antibiotics. Controlled trials (Q33-26) would be required to evaluate the potential benefit of antibiotics for dysfunctional uterine bleeding.

K: Hyoscine butylbromide, (Buscopan)

This agent relaxes smooth muscle and therefore reduces uterine contractions. It may be considered in the management of dysmenorrhoea.

L: The levonorgestrel intrauterine system (

Mirena)