Treatment of Fibroids with Medication

There are medical drug treatments for fibroids which include prescription and non-prescription drugs. There are medications that can control fibroid pain and bleeding. Some drugs will shrink fibroids but these can have serious side effects if used for more than a few months.

Treatment for uterine fibroids that doctors offer fall into 2 categories: treatment with drugs or surgery. Generally doctors prefer medications over surgery because the risks are less. In some cases surgery can relieve symptoms more effectively but surgery is usually more dangerous. The results of taking medication are usually reversible but surgery is not. Doctors therefore usually recommend medication before surgery. One mistake that gynaecologists make is not offering women drug treatment for their fibroids before advising a hysterectomy. If you try medications for your uterine fibroids and the treatment doesn’t work then you haven’t lost much. You may spend a few weeks trying the medication but otherwise you are no worse off than when you started. If you have surgery and develop a complication you may have to live with the consequences of that complication for the rest of your life. Surgery is the best option in some circumstances but it is best to try medication first.

Medication to control symptoms of fibroids 

Medications can be so effective that some women are able to live with their fibroids and never need surgery. Fibroid pain and bleeding can often be controlled with analgesics, oral contraceptives, or other hormones or in some cases a combination of drugs.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)

A commonly used group of drugs used for fibroid pain is NSAIDS. These drugs work by reducing inflammation and they are not steroids. Examples include aspirin or ibuprofen (Advil, Motrin, Nurofen-in UK). These are often the best first choice for fibroid pain or pelvic cramps. Aspirin can worsen bleeding and is best avoided if heavy periods are a problem. Other NSAIDS such as mefenamic acid (Ponstel, Ponstan- in UK), diclofenac (Voltaren, Voltarol-in UK), naproxen (Naprosyn) require a prescription. They are effective for fibroid pain, pelvic cramps, pressure or pain in the pelvic region and may help reduce menstrual flow.

Mefenamic acid is commonly prescribed for period pains and fibroid pain. These drugs have been in use for many years and are reasonably safe. The main side effect is gastric irritation. They should always be taken with food. The beneficial effect of NSAIDS can be even greater when used with the oral contraceptive pill. NSAIDS work by lowering the levels of a chemical called prostaglandin. This chemical is present in large amounts in menstrual blood. Prostaglandin stimulates uterine contractions and causes fibroid pain. NSAIDS are effectivein reducing pain and inflammation. Other side effects of NSAIDS apart from indigestion include: heartburn, nausea, diarrhoea, constipation, fluid retention and gastro-intestinal bleeding. Taking NSAIDS long-term can causes gastro-intestinal problems, kidney problems and high blood pressure. However these risks must be weighed against the risks of surgery or uterine fibroid embolization.

Oral Contraceptive Pill (Birth control pill)

Taking the oral contraceptive is a commonly prescribed medication for heavy bleeding and pain associated with fibroids. It is also often taken by women for heavy periods who do not have fibroids. Birth control pills contain the female hormones estrogen (oestrogen in UK) and progesterone. These hormones help to stabilize the endometrium (lining of the womb), the part of the uterus that bleeds and therefore reduce the bleeding that occurs with menstruation.

These pills have been shown to work as well as NSAIDS and Danazol (an even stronger drug). Oral contraceptives are usually prescribed for 3 weeks with a 1 week break. It has been found that it is safe to take the pill for longer and have a break every 3 months. Some doctors will recommend this way of taking the pill. Always discuss your treatment with your doctor and do not initiate changes yourself. Birth control pills contain hormones that may affect the growth of fibroids. Some studies have shown that the oral contraceptive pill may protect against fibroids. But other studies have not confirmed this. More studies are needed on the effect of the birth control pill on fibroid growth. If you have fibroids and are taking the contraceptive pill you should have the size of your fibroids monitored by your gynaecologist.

Some doctors will advise against taking the contraceptive pill if you have fibroids, but most doctors disagree with this and the weight of evidence suggest that taking the birth control pill does not enlarge fibroids and does help to control symptoms. There are some women who are at increased risk of side effects from taking the contraceptive pill. E.g. women with high blood pressure, liver disease, those with a history of blood clots (DVT or pulmonary embolism). These women should discuss their medical history with their doctor.

Tranexamic Acid

Tranexamic acid (Cyklokapron) is a drug that reduces bleeding. It is an antifibrinolytic and works by preventing blood clots from dissolving. It was originally used for controlling heavy bleeding in patients with haemophilia. The U.S. Food and Drug Administration (FDA) approved tranexamic acid oral tablets (Cyclokapron, Lysteda) for treatment of heavy menstrual bleeding on 13 November 2009. In March 2011 the status of Tranexamic acid for treatment of heavy menstrual bleeding was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines) and became available over the counter in UK pharmacies under the brand names of Cyclo-F and Femstrual. This drug has shown to significantly reduce menstrual blood flow. It has been shown to be more effective than Provera (a progesterone) and NSAIDs. It has shown to be effective in women with heavy bleeding due to uterine fibroids.

Tranexamic acid appears to have fewer side-effects but about 30% of women experience nausea or leg cramps. Initially there was concern that tranexamic acid would increase the risk of blood clots but this has not been found to be the case in practice. The drug is only taken on days when menstrual blood flow is heavy.

Progestin (Progesterone)-Releasing IUD

There are intrauterine devices (coils) that release progestin (progesterone) slowly. They are effective in reducing menstrual bleeding in women who have heavy periods. They are used more widely in Europe than the USA. A couple of studies of progestin releasing IUDs, have shown a reduction in bleeding of up to 90%. A study which was published in the Lancet in 2001 took two groups of women who were treated with either a hysterectomy or progestin IUD. The study showed that progestin IUDs are successful in reducing menstrual bleeding in most women. The success rate of controlling bleeding by hysterectomy was 100%. The progestin releasing IUD was successful in significantly reducing bleeding in about 70% of women.

In the United States there is one progestin releasing IUD available on the market. This is the Mirena IUD. It releases levonorgestrel, which is a type of progestin that has been found to reduce heavy menstrual bleeding. The Mirena IUD can be left in the uterus for up to 5 years. The Mirena IUD is widely used in the United Kingdom and Europe. IUDs are much less popular in the United States because of problems with the Dalkon Shield, an IUD that had to be taken off the market in 1975. The problem with the Dalkon shield was the design of that particular IUD. The Mirena IUD is extremely safe and there are few reported side-effects. It has been found that women who have used a progestin releasing IUD tend to develop less fibroids than those who use other types of IUD. One study looked at the risk of developing fibroids whilst using an IUD several hundred women were studied and over the course of eight years 14 women who used non-hormone releasing IUDs developed fibroids, but none of the women who used progestin releasing IUDs developed uterine fibroids. If a woman with fibroids requires an IUD then fitting this IUD may be difficult. If you have fibroids and wish to have an IUD fitted then it is best to see a physician who is experienced in fitting IUDs in women who have fibroids.

Medication that can shrink fibroids

There are a number of drugs that are able to shrink fibroids but the problem is that their effect wears off when the medication is stopped. These drugs are able to change the level of various hormones in the body. The most widely used medications are gonadotropin releasing hormones (GnRH) or GnRH agonists. Examples of gonadotropin releasing hormone agonists include Lupron and Zoladex.

Other types of drugs that can shrink fibroids include hormone antagonists and receptor blockers, interferon, synthetic steroids and selective estrogen receptor modulators. Some of these drugs are experimental and usually only prescribed in trials.

Gonadotropin releasing hormone (GnRH)

Gonadotropin releasing hormone controls the release of two hormones from the pituitary gland. These hormones are FSH and LH. The hormones FSH and LH control the production of follicles by the ovaries and changing levels of these two hormones regulates the female menstrual cycle. Drugs have been developed which act like gonadotropin releasing hormone.These drugs are called GnRH agonists and are much more potent than the natural gonadotropin releasing hormone. The drugs control the normal GnRH bursts of hormone and the amount of oestrogen and progesterone produced by the ovaries. This has the effect of causing the menstrual periods to stop and also to cause fibroids to shrink in most women. The effect of these drugs varies between women and in some women the fibroids shrink almost completely whilst in others there is no response at all. 

Gonadotropin releasing hormone agonists usually take about two weeks to start working. After three months of treatment fibroids typically have shrunk in size by between 30 to 50%. Unfortunately, uterine fibroids usually return to their original size 3 months after the drug is stopped. Continued use of these drugs can lead to osteoporosis because the drug prevents normal oestrogen production. There is also a theoretical risk of increased risk of a heart attack due to lowered levels of oestrogen. These drugs are therefore only suitable for short-term usage. Examples of gonadotropin releasing hormone agonists include leuprolide (Lupron), nafarelin (Synarel) and goserelin (Zoladex). a problem with these drugs is that they are ineffective if taken by mouth. This is because GnRH is destroyed by the stomach acid. Therefore the medication as to be given by nasal spray or injection. There are slow release injection formulations of these drugs which will remain effective for either one month or three months. Synarel is a nasal spray usually administered twice a day.

These drugs are often used to stop menstrual periods for a while, particularly if the periods are very heavy and have led to iron loss and anaemia. Women with fibroids can be prone to heavy periods and therefore are prone to develop anaemia. If surgery is planned for your fibroids and you are suffering from heavy periods and anaemia then use of these drugs is extremely beneficial in enabling you to recover from the anaemia and prepare for surgery.

These drugs are also often used to shrink fibroids to a more manageable size prior to surgery. GnRH agonists can also be used to keep fibroids under control if the menopause is believed to be imminent. This is only safe as a strategy if you and your doctor think you will be entering the menopause within the next six months.

GnRh agonists have side effects such as hot flushes, reduced sex drive, vaginal dryness, weight gain, loss of calcium and other minerals from bones (leading to osteoporosis) and depression. Other less frequent side-effects include insomnia, headache, painful intercourse, muscle pain, weight loss, hair loss and fluid retention. These side-effects can be treated by taking a low dose of oestrogen or a synthetic progesterone substitute.

Osteoporosis is a major concern when these drugs are used for longer than 3 to 6 months. Most doctors who prescribe GnRH agonists for longer than 3 to 6 months will also prescribe HRT treatment to these women. Taking HRT adds back a low dose of oestrogen and sometimes progesterone. This helps to prevent osteoporosis. Many women have slight menstrual bleeding two days to 2 weeks after starting gonadotropin releasing hormone agonists. This is normal and periods then typically stop after this episode of bleeding. However an estimated 20 to 30% of women continue to experience slight intermittent vaginal bleeding. A few women will continue to have heavy bleeding although this is unusual.

Mifepristone

Mifepristone which is also known as RU-486 is a synthetic steroid hormone that suppresses progesterone and glucocorticoids. The brand name of Mifepristone is Mifeprex.this drug works by blocking progesterone and because fibroids require progesterone to grow it has been found that Mifepristone causes fibroids to shrink. Studies have shown that mifepristone is effective at decreasing uterine blood flow and shrinking fibroids.several randomised controlled studies have found that mifepristone taken in a dose of five or ten milligrams daily for three months can shrink fibroids by 25 to 75%. Women who were taking mifepristone had a good reduction in symptoms including decreased pelvic pain and menstrual bleeding.

Mifepristone has less side effects than gonadotropin releasing hormone agonists. There are however some side-effects. Some patients experience hot flushes during the first month of treatment and a few experience a brief and temporary increase in joint pain. Other side-effects include minor reversible changes in liver function tests and uterine hyperplasia. Uterine hyperplasia is temporary overgrowth of the lining of the uterus. If mifepristone were to become a standard treatment for fibroids over the long-term then it would have to be taken daily. At present more research needs to be done into the effects of taking mifepristone long-term. The initial short-term studies have produced interesting and exciting results but it is still too early to recommend mifepristone as a standard long-term treatment for fibroids.

Tamoxifen and Raloxifene

Tamoxifen and raloxifene are called selective estrogen receptor modulators (SERMS). They are sometimes known "as designer drugs" and they have a complex effect on estrogen receptors. They are generally estrogen receptor antagonists but they have an agonist effect on estrogen receptors in the uterine endometrium. They are therefore a mixed estrogen receptor agonist/antagonist.

They were initially developed as a treatment for breast cancer. This is because many types of breast cancer are sensitive to oestrogen and Tamoxifen is able to block the effect of oestrogen on breast tissue. Tamoxifen is also used to prevent breast cancer from developing in women who are thought to be at high risk. Women who take Tamoxifen have a higher risk of endometrial hyperplasia and it is even thought of developing endometrial cancer.

Many women have taken Tamoxifen to treat or prevent breast cancer and studies have been carried out on the effects of Tamoxifen on fibroids in some of these women. in a small study which was published in the Journal of ultrasound medicine 17 postmenopausal women who were taking tamoxifen for breast cancer were followed up and had regular uterine ultrasound scans. At the start of the study 13 of the women were known to have at least one fibroid. During the course of the treatment with tamoxifen six of the women developed new fibroids. The women did not have symptoms from the fibroids but the overall size of the fibroids seemed to increase. This study suggests that tamoxifen is probably not a good treatment for fibroids.

Raloxifene is a selective oestrogen receptor modulator like tamoxifen. Its main use has been in post menopausal women to treat and prevent bone loss. It is thought to be effective in preventing osteoporosis since it works as an oestrogen agonist. A study published in the Journal of fertility and sterility by Dr Stefano Palomba in 2001, looked at 70 postmenopausal women who were affected by uterine fibroids. They were treated with raloxifene 60 mg daily for 12 months and the fibroids were significantly decreased in size after 12 months. Raloxifene was not found to cause thickening of the endometrium in these women. this study is one of the most promising investigations of drug treatment uterine fibroids but unfortunately the results were only seen in postmenopausal women.

More research needs to be done into the effect of raloxifene in shrinking fibroids.

Androgen Therapy

Danazol is an older synthetic steroid that is chemically similar to testosterone. It is a derivative of the synthetic steroid ethisterone. Danazol reduces levels of oestrogen and prevents ovulation and menstruation. It has been used as a treatment for menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura, breast pain and hereditary angioedema. Danazol has been studied as a treatment for uterine fibroids and it has not been found to shrink uterine fibroids. The Cochrane uk review concluded that the benefits of danazol outweigh its risks in treating uterine fibroids.

Gestrinone is an androgen like steroid hormone which acts like an anti-progestin. Gestrinone is not available in the USA. It is used as a treatment for endometriosis in the UK. It is available in many countries and has been studied in Europe where at least three studies have investigated the effects on women with fibroids. It was found that gestrinone resulted in a decrease in size of uterine fibroids in about two thirds of women who took it. In one study it was found that the fibroids shrank by an average of 40% after one year of treatment and did not immediately regrow. About 90% of women maintained their decrease in uterine size for 18 months. Unfortunately there was a high incidence of masculinizing side-effects. These included body hair growth, voice deepening, acne , weight gain and fluid retention. These unacceptable side-effects make it unlikely that gestrinone will become a useful treatment for fibroids.

Interferon

Interferons are proteins produced by host cells in response to pathogens such as bacteria and viruses or tumour cells. They are effective anti-viral and anti-tumour drugs. Laboratory studies have shown that interferon alpha and interferon beta are potentially beneficial in treating fibroids. Trials on humans have not been undertaken to study the effect of interferon on fibroids. A study in 1998 reported in the American Journal of reproductive immunology showed that interferon alpha is a potent inhibitor of basic fibroblast growth factor stimulated cell proliferation in human uterine cells. In a case reported in the medical literature a woman with hepatitis C was treated with interferon for seven months. In addition to hepatitis C, she had a fibroid which shrank in size from 202 cm³ to 29 cm³. The fibroid continued to shrink even after the interferon therapy was discontinued.

Interferon has significant side-effects and is a very expensive drug. Interferon would have to be researched and developed specifically as a treatment for uterine fibroids thoroughly before it can be recommended as a treatment option for uterine fibroids.