PROLONGED AND HEAVY MENSTRUAL BLEEDING: MEDICAL TREATMENT

CONTENT

-INTRODUCTION

-INDICATIONS FOR MEDICAL TREATMENT OF HMB

-NON HORMONAL DRUGS/MEDICATIONS

-HORMONAL DRUGS/MEDICATIONS

 

INTRODUCTION

Quite often, the medical treatment of HMB due to pelvic disorders is temporal until a permanent solution is sought e.g. surgery for HMB due to uterine fibroid, or for a short period of time till the woman enters menopause. For HMB due to DUB, because the bleeding hardly changes over time, medical treatment is usually indicated for a very long time unless it fails after which the medication is either changed or a surgical treatment is offered. With so many arrays of possible drugs to choose from, extensive consideration concerning the choice of medication must put into perspective the efficacy and the side effects of each drugs before settling for any particular one. 

 

INDICATIONS FOR MEDICAL TREATMENT OF HMB

1.  HMB in women without any pelvic pathology i.e women with DUB.

2.  HMB in women desirous of fertility.

3.  HMB in women with or without pelvic diseases that is not fit for surgery.

4.  HMB in women been prepared for but not yet ready for the surgery.

5.  HMB in women who decline surgical intervention.

The drugs used in medcal treatment can be divided into two main classes as follows:

 

 NON HORMONAL MEDICATIONS

These are drugs which act to reduce menstrual flow by acting via any other means other than a direct influence on the HPO axis. They include various groups of drugs such as antifibrinolytics e.g.Tranexamic acid and Epsilon-amino caproic acid, Non steroidal anti-inflammatory drugs (NSAIDs) e.g Ibuprofen, Mefenamic acid, Naproxen and Diclofenac among many others and Etamsylate

1.  NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

Just as in primary dysmenorrhea, prostaglandins have been implicated in the genesis of menorrhagia. NSAIDs are potent inhibitors of the cyclooxygenase enzymes necessary for the production of prostaglandins. They include mefenamic acid, naproxen, ibuprofen, diclofenac and feldene (piroxicam) just to mention a few. With similar efficacy, depending on the dosage used for specific agents, they produce about 20 to 45% reduction in the menstrual blood flow. They are also effective in reducing blood flow in women on a copper or non-hormonal intrauterine contraceptive device as well in alleviating symptoms due to dysmenorrhoea

They are typically used for 5 days or until cessation of menses starting from the first day of menses. Their common side effects include gastrointestinal irritation resulting in peptic ulcers and a significant increase in bleeding from surgical or traumatic wounds. They may make it difficult to conceive due to inhibition or prevention of ovulation (LUF syndrome) when used close to the ovulation period. They are contraindicated in women with a history of duodenal ulcer or severe asthma. A common example is Mefenamic acid, 500 mg taken three times a day for five days at the beginning of each menses or when the menstrual flow is particularly heavy or painful.

2.  TRANEXAMIC ACID

Wherever a significant bleeding occurs in the human body, two sets of interplaying systems or factors are activated simultanously both influencing the rate of bleeding. The first system is involved in promotion of the blood clots necessary to reduce or stop bleeding  at the site of profuse bleeding. These are referred to as the clotting system. The second system is involved in the prevention of formation of excessive blood clots during bleeding essential in limiting the formation of blood clots just within the site of bleeding. These are reffered to as the fibrinolytic system. They include specifically plasmin and its activators. A normal balance is kept between both systems to prevent excessive bleeding on one side or excessive blood clotting on the other side. Women with HMB have been noticed to have increased fibrinolytic activity in their endometrium.

Tranexamic acid is an antifibrinolytic agent, which acts by inhibiting the fibrinolytic system, thereby reducing excessive blood loss from the endometrium. At a total dose of about 2 to 4 g/day for 4 to 7 days during the menstrual period, it reduces menstrual blood flow by up to 50% over two to three cycles. This is superior to the effect of NSAIDs such as mefenamic acid, feldene and ibuprofen. Similarly, it is effective in women on copper or non-hormonal intrauterine devices and only requires to be taken on days when the bleeding is particularly heavy. It has no effect on ovulation and conception and so, it is compatible with ongoing attempts at conception. It is well tolerated with few side effects mainly limited to mild gastrointestinal complaints. The fear of increased formation of blood clots in pregnancy due to excessive clots formation have been debunked by multiple researches and it is therefore safe in pregnancy. Another medication with antifibrinolytic activity is Epsilon-aminocaproic acid.

 

HORMONAL MEDICATIONS

These are drugs which when used affect the HPO axis directly or indirectly by influencing the hypothalamus, pituitary gland, ovaries and the endometrium. They include progestogens, oral contraceptives, hormone replacement therapy, danazol, gestrinone and GnRH analogues.

PROGESTOGENS

These may be divided into oral, intrauterine and intramuscular depot injections based on the route of administration. 

1.  NORETHISTERONE

This is probably the only widely known orally administered progestogen effective in controlling HMB when taken in a cyclical pattern. It is recommended in dosage of 5–10 mg three times a day from the 6th day of the menstrual cycle to the 26th day of the menstrual cycle or simply for 21 days from the end of one’s menstrual flow. It’s drawback however is that it occasionally causes break-through bleeding and is not an effective contraceptive. Other known side effects include weight gain, headache and bloatedness.

2.  MIRENA (LNG-IUS)

This is an intra uterine device embedded with a progestogen (lervonogesterol) originally designed for contraception. It is an excellent means of contraception that can reduce menstrual blood loss by up to 96%. About 20% of women using it will report a total cessation of menstrual flow within 1 year of use and about another 65% will continue to report improve menstrual bleeding over a 3-year period. It is comparable in effectiveness to most surgical methods of controlling HMB and can serve as an alternative to hysterectomy. When compared to hysterectomy, it is cheaper and has the capacity to reduce the need for hysterectomy in many women with HMB. It does not only preserve a woman’s fertility, it is also associated with an instantaneuos reversal of contraception once removed. It may serve as a source of the progestogen needed for systemic hormone replacement therapy (HRT) in women nearing menopause. It can also alleviates symptoms of dysmenorrhea and reduce the incidence of pelvic inflammatory disease. It is associated with frequently occurring variable bleeding and spotting of blood from the vagina, particularly within the first three to nine months of use similar to many other progestogens. However it lacks most of the systemic side effects of other progestogens such as weight gain, bloatedness, acne, and head aches because it is restricted within the uterus both in location and action. Occasionally, it is associated with the development of mainly asymptomatic ovarian cysts that often resolves spontaneously after removal of the IUD.

3.  MEDROXY PROGESTERONE ACETATE

This is one of the few intramuscular injectable progestogen usually taken on a three monthly basis specifically for the purpose of contraception. It is not a popular means of controlling HMB as its effectiveness is questioned by its highly variable and unpredictable pattern of bleeding. Occasionally, it may come in handy as it has the property to halt acute heavy bleeding in woman with HMB by inducing endometrial atrophy. However, because of its atrophic effect on the endometrial cells, it is important to exclude endometrial hyperplasia in women at risk of endometrial hypertrophy before its use, as it can affect the histology of the endometrial lining if a biopsy were taken after using the medication. It is also associated with significant weight gain, bloatedness and many other side effects of systemic progestogens. It does have a role as a palliative means of reducing bleeding in women with abnormal bleeding from endometrial cancer not responsive to chemotherapy.

4.  COMBINED ORAL CONTRACEPTIVE PILLS

The daily oral combination contraceptive pills when used cyclically produces a controlled much reduced regular bleeding in patients with HMB. Doubling up as a very effective contraceptive when taken properly, continous usage of the active pills for two to three months known as bicycling or tricycling, can produce controlled bleeding once in two to three months further reducing excessive and frequent bleeding. It provides symptomatic relief of dysmenorrhea for patients with co-existing HMB and dysmenorrhea. It is contraindicated in women with known risk factors for thromboembolism as well as patients over 35 years old who smoke. It is also contraindicated in women with a personal or family history of breast cancer. Similarly, due to its tendency to induce weight gain, it is unsuitable for women who are grossly overweight.

 

ANDROGENS

These are drugs either derived from or share masculinizing properties with the male hormone testosterone. They act on the endometrium, ovary, and hypothalamus to oppose the effect of the female hormones necessary for control and regulation of the menstrual cycle and the formation of the menses. They induce about 80% reduction in menstrual blood loss and they are quite effective in controlling HMB. Their use is however limited by their androgenic or masculinizing side effects which include balding, hoarseness of voice, hirsutism and acne, among many others. Examples are danazol and gestrinone.

 

GnRH AGONISTS

These are centrally acting drugs that act on the pituitary gland to stop completely the production of oestrogen  from the ovary resulting in complete cessation of menstruation.Because they induce changes in the body similar to menopause, their effects are described as akin to a medical menopause. They are also effective for the management of dysmenorrhoea. Although 100% effective in controllong HMB similar to hysterectomy, they are used for a very short period of time because the induced medical menopause is associated with a lot of a adverse effects associated with the complete absence of oestrogen production in the body when used over a long period of time.

Top on the list of side effects include an asssociated increased loss of bone mass leading to the thinning of bones and increased incidence of both provoked and sudden unprovoked bone fractures. Other side effects are hot flushes, sweating, painful intercourse or dyspareunia due to reduced wetness of the vagina, restlessness, irritabilty and occasional irregular bleeding. External oestrogen source can be given as a form of hormone replacement therapy for the acute deficiency in oestrogen a process often referred to as add back therapy, to reduce the side effects of the drugs. Examples include Goserelin (Zoladex), Decapeptyl (Triptorelin) and Buserelin (Suprecur).

 

MIFEPRISTONE (RU-486)

This is an anti-progestational agents, i.e. a drug that blocks the effect of progesterone hormone in the body. It is a common abortificient that is effective at an early age of pregnancy up to about 49 days that is banned in the Nigerian open market as well as many other countries with restrictive law against abortion. It was however noticed to inhibit or prevent ovulation and to disrupt the endometrial integrity thus resulting in complete cesssation of menstrual blood flow and hence theoretically suitable for the treatment of HMB. It has also been reported to reduce or shrink uterine fibroids size. It’s use for the tretment of HMB is however limited due to its associated incresed risk of endometrial hyperplasia, another possible cause of HMB that can occasionally progress to endometrial cancer.

Since menstrual loss, in women with HMB secondary to DUB, does not change markedly over time, the treatment here is often  for a long time. Women should remember that these drugs act temporarily and only works for the duration of time they are being used. When a more permanent, one time fix is required, a surgical approach should be considered, Similalrly, If no improvement in seen after about 3 months of use, women should be given a surgical option or a change of medication. Medical treatments for HMB due to pelvic diseases such as PID and uterine fibroids will be discussed in their respective sections on this site. But for further information, kindly please chat with our consultants.

 

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