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Menstruation: Heavy Bleeding (Menorrhagia)

Description

An in-depth report on the causes and treatment of heavy periods.

Alternative Names

Bleeding: menstrual; Menstrual Disorders

Medications

Drug therapy can be very useful for many women with menorrhagia. It should be strongly noted that up to half of women who report heavy bleeding do not actually lose abnormal amounts of blood. A correct diagnosis of true menorrhagia is very important, since the treatments, both medications and surgery, can have severe side effects. Women should feel confident that they understand all of their options and exercise their own treatment preferences. A general drug treatment regimen for menorrhagia is as follows:

Nonhormonal Agents. The use of nonhormonal agents is an appropriate first choice when the menstrual cycle is regular.

  • The first options are nonsteroidal anti-inflammatory drugs, with reported reductions in menstrual blood loss of 25% to 35%.
  • Tranexamic acid is a drug that enhances blood clotting and is used more in Europe than in the US. It is proving to be very effective, and women might ask their physician if it is available.

Hormonal Agents. Hormonal agents are useful for women with heavy bleeding who also want to control the menstrual cycle.

  • The best choice for women who also want effective birth control is either the combined oral contraceptive pill or a progestin containing intrauterine device. The levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena, FibroPlant) specifically is proving to be a particularly effective treatment for menorrhagia and may reduce the need for surgery in many women.
  • Danazol and the gonadotropin-releasing hormone (GnRH) analogues are highly effective for more severe cases, but their side effects make them suitable only for short-term use. These agents are also useful as pretreatment before procedures used to destroy the uterine lining. Both are effective, but GnRH analogues may be slightly better.

Nonhormonal Agents

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins (the substances that increase uterine contractions). They also have other properties that act against inflammatory factors that may be responsible for heavy menstrual bleeding. Studies suggest that they reduce bleeding by 30% to 50% and are the first choice for most women who experience heavy menstrual bleeding. Aspirin is the most common NSAID, but there are dozens of others available over the counter or by prescription. Among the most effective NSAIDs for menstrual disorders are ibuprofen (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and mefenamic acid (Ponstel). Mefenamic acid has been intensively studied and has been shown to reduce bleeding by 30% to 50%. In one major 2002 analysis, NSAIDs were equally or more effective than oral contraceptives or progestins. (They weren't as effective as tranexamic acid or danazol.) For maximum benefit, they should be taken seven to 10 days before a period is expected. It should be noted, however, that long-term use of any NSAID can increase the risk for gastrointestinal bleeding and ulcers. In fact, one 2001 study of women with iron deficiency anemia reported that overuse of NSAIDs for menstrual disorders contributed to the anemia.

Tranexamic Acid. Tranexamic acid (Cyclokapron, Transamin, Exacyl, Cyklo-f) is a synthetic form of the amino acid lysine and enhances blood clotting. It reduces menstrual blood flow by about half. It is more effective in reducing blood flow than oral progestins or NSAIDs, but is not as effective as the progestin-releasing IUD (LNG-IUS). Women reported a better quality of life with tranexamic acid than with oral progestins. Side effects, however, can include headache, nausea, and gastrointestinal distress. Tranexamic acid may be a good treatment choice for menorrhagia not caused by fibroids, endometriosis, or other uterine lesions and when hormonal agents are not an option.

There is some concern that it may increase the risk for blood clots, but a long-term Swedish study reported that it posed no higher than average risk for blood clots. (Nevertheless, women with any risk factors for blood clots should not use this agent.)

Combination Oral Contraceptives

Oral contraceptives (OCs), commonly known collectively as "the Pill," contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestogen). These agents block production of male hormones and inhibit receptors for estrogen in the uterus. OCs are often used to regulate periods in women with menstrual disorders, including menorrhagia (heavy bleeding), dysmenorrhea (severe pain), and amenorrhea (absence of periods). They also protect against ovarian and endometrial cancers. It is not clear, however, if they are any more effective than NSAIDs in reducing heaving bleeding, but they may still be a good option for women seeking both birth control and relief from menorrhagia.

Combination pills are sold in 21-day or 28-day packs:

  • Each pill in the 21-day pack contains the necessary estrogen and progestin.
  • The 28-day pack adds seven differently colored reminder pills; they are inactive and do not contain hormones, but help the user maintain her daily routine during seven days between active pill use.

OCs may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase).

  • Monophasic regimen (e.g., Alesse, Brevicon, Demulen, Desogen, Genora, Levlen, Levlite, Loestrin, Lo/Ovral, ModiCon, Necon, Nordette, Norethin, Norinyl, Ortho-Cyclen, Ortho-Novum, Ovcon, Ovral, Yasmin, Zovia.) A 21-day pack uses tablets that are one strength and one color for 21 days. (A 28-day pack adds seven inactive tablets of a different color.)
  • Biphasic regimen (e.g., Mircette, Necon, Nelova, Ortho-Novum). A 21-day pack consists of tablets of one strength and color taken for seven or 10 days, then a second tablet with a different strength and color for the next 11 or 14 days. (And a 28-day pack adds seven inactive tablets of a third color.)
  • Triphasic regimen (e.g. Estrostep-21, Ortho-Novum 7/7/7, Ortho Tri-Cyclen, Tri-Levlen, Tri-Norinyl, Triphasil, Trivora). This pack consists of tablets with three different colors and strengths. In the first phase, there are tablets of one color for five to seven days; for phase two, a second color and strength tablets is taken for five to seven days; and for phase three, a third color and strength tablet is taken for five to 10 days. The difference in duration of each phase depends on the brand. (And a 28-day pack includes a fourth color inactive tablet for the last seven days.)

In all cases, women continue to menstruate, but their periods are lighter, shorter, more regular, and less painful than bleeding in women who are not on the pill. The monophasic regimen is the most studied regimen and at this time is preferred. Yasmin, one of the monophasic forms, contains drospirenone, a progestin that resembles the natural form. Studies suggest that it may help reduce dysmenorrhea as well as premenstrual symptoms. There appears to be no major differences in bleeding control between the monophasic and biphasic regimens. One analysis found better bleeding control with the triphasic than the biphasic, which may have due to the specific progestins used (levonorgestrel in the triphasic regimen and norethindrone in the biphasic regimens).

Some researchers are investigating continuous oral contraceptives, either by extending a monophasic regimen or by using specific agents (e.g., Seasonale, which contains estrogen and levonorgestrel). This approach produces a period only about every three months. Continuous OCs have the potential for helping women with either heavy bleeding, painful periods, or both. Breakthrough bleeding is the most common side effect. In fact, although there are fewer actual bleeding days with the continuous OC, total days of spotting plus bleeding are no different from other OCs regimens. In one 2003 study, women were equally satisfied with both the continuous and standard OC regimens. This approach is not suitable for women who frequently miss taking their pills. Long-term effects of steady hormone use are not known, and continuous contraceptives are still in trials.

Estrogen and progestin each cause different side effects. Uncommon but more dangerous complications of OCs include high blood pressure and deep-vein blood clots (thrombosis), which may contribute to heart attacks or strokes. It should be noted that a long-term study of 46,000 British women found no difference in mortality rates between women who took OCs and those who did not. The most serious side effects are due to the estrogen in the combined pill. Women at risk can usually take progestin-only contraceptives.

Other Forms of Combination Contraceptives. Other methods for delivering contraceptives include skin patches, monthly injections, and vaginal rings. It is not clear, however, if they have any advantages for women with heavy bleeding.

Progestins

Progestins (either natural progesterone or synthetic progestogen) are used by women who clearly have dysfunctional uterine bleeding caused by unopposed production of estrogen. A number of forms are available and have specific advantages and disadvantages. In addition to reducing bleeding, another important advantage is that they appear to protect against uterine and ovarian cancers. It should be noted that some progestin treatments, such as implants, can cause menorrhagia in the first few months. Progestins can be delivered in various forms.

Progestin-Releasing IUDs. Intrauterine devices (IUDs) that release progestin may be very beneficial for menstrual disorders. Specifically, the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena, FibroPlant) is proving to have important effects on menstrual disorders, regardless of its contraceptive effects. The LNG-IUS is now considered to be one of the best options for treating menorrhagia. Some studies suggest it might help avoid hysterectomy in 80% of cases. It also reduces pain and may help prevent endometriosis. One expert described the LNG-IUS as a nearly ideal contraceptive.

The Mirena is the current standard brand. FibroPlant is a unique "frameless" LNG-IUS device that is very small and secretes a very low dose of progestin. It appears to have very few hormonal effects, although comparison studies are needed to prove any significant advantages over the Mirena.LNG-IUS releases progestin for up to seven years. Progestin released by an IUD mainly affects the uterus and cervix and so it causes fewer widespread side effects than the progestin pills do. (It should be noted that the other major IUD--the Copper T--may increase bleeding.)

Irregular break-through bleeding can occur for the first six months, but afterward 80% to 90% reduction in blood loss has been reported. It is well tolerated. It may even be appropriate and protective for women with uterine fibroids, but studies to date suggest it is less effective in reducing menstrual bleeding from fibroids than from other causes. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually do not cause symptoms and resolve on their own.

Oral Progestins. Oral progestins include medroxyprogesterone (Provera, Amen, Curretab, Cycrin), norethindrone acetate (Aygestin, Norlutate, Micronor), and norgestrel (Ovral). Taking such agents for 21 days is effective in reducing bleeding. Oral progestins, however, have unpleasant psychological and physical side effects such as bloating, depression, moodiness, and breakthrough bleeding.

Natural progestins (called progesterone) may be helpful. A natural oral form of finely ground (micronized) progesterone (Prometrium), which is made from wild yams, is also available and has fewer side effects.

Injections (e.g., Depo-Provera). Depo-Provera uses a progestin called medroxyprogesterone. Unlike users of the implants, most users of Depo-Provera stop menstruating altogether after a year. It may be beneficial for women with heavy bleeding, severe cramps, or both. Women who eventually want to have children should be aware that Depo-Provera can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months. Weight gain can be a problem, particularly in women who are already overweight. Of some concern was a 2002 study that found changes in the arteries of long-time users suggesting a risk for future heart disease. More research on this finding is warranted.

Hormones Used in Contraceptives

Estrogen (Estradiol)

Estrogen is the major female hormone and is responsible for female characteristics. The estrogen compound used in most oral contraceptives is estradiol and is always used with a progestin.

Effects on Reproduction. When used throughout a menstrual cycle with progesterone, it suppresses the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevents ovulation. Estrogen also changes the cellular structure of the lining of the uterus (the endometrium) and hinders implantation of a fertilized egg.

Side Effects of Estrogen. During the first two or three months of use of oral contraceptives, side effects from estrogen in the combined pill includes:

  • Nausea and vomiting. (Can often be controlled by taking the pill during a meal or at bedtime.)
  • Headaches. (In women with a history of migraines, they may worsen.)
  • Dizziness.
  • Breast tenderness and enlargement. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer, and if it does, which women are at risk. A reassuring 2002 study supported an earlier major study, with both finding no evidence that OC use increases the risk for breast cancer, even in women who have taken them for 15 years or more or had taken them at young ages. Still, more research is needed to verify these findings, given previous reports of a slightly higher risk.
  • Estrogen has mixed effects on heart. It appears to improve cholesterol and other lipid levels. However, it also increases blood clotting and may increase the risk for stroke in certain women. New OC preparations with estrogen at lower doses (20 mcg and below) may reduce these side effects, and improve the effects on heart and circulation. Such preparations, however, may also increase spotting and break-through bleeding, depending on the progestin used.

[Also seeWell-Connected Report #91 Contraceptives: Female.]

Progesterone (Progestin)

When used in contraception, progesterone is referred to by one of several names:

  • Progesterone is actually the name for the natural hormone.
  • Progestogen is a synthetic form.
  • Progestin is the term for any agent, natural or synthetic, that causes progesterone effects. It is used as the general term in this report.

Effects on Reproduction. Progestins may be used alone or with estrogen in oral contraceptives. In addition, certain specific progestins are used in other kinds of contraceptives, such as levonorgestrel in implant systems and depo-medroxyprogesterone acetate in the injected Depo-Provera.

Progesterone can prevent pregnancy by itself in a number of ways:

  • It blocks luteinizing hormone (LH), one of the reproductive hormones important in ovulation.
  • It maintains a powerful barrier against the entry of sperm into the uterus by keeping the cervical mucus thick and sticky.
  • It reduces the motility in the fallopian tubes, thereby inhibiting sperm transport.
  • It changes the lining of the uterus and makes it more difficult for the fertilized egg to implant.

Progestins used in contraceptives are referred to as:

  • Second generation (e.g. levonorgestrel, norethisterone).
  • Third generation (e.g. desogestrel, gestodene, norgestimate, drospirenone). The third generation progestins tend to have fewer male-like side effects. Some studies suggest, however, they may pose a higher risk for blood clots than the older progestin, although the risk is still small. They possibly may have a better effect on cholesterol levels than earlier progestins, but this does not seem to translate into any particular heart benefits.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that only uses progestin, although they may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include the following:

  • Changes in uterine bleeding. Such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods. Be sure to check with the physician if any of these occur.
  • Unexpected flow of breast milk. (Check with the physician if this occurs to be sure other abnormalities are not causing it.)
  • Abdominal pain or cramps.
  • Diarrhea.
  • Fatigue, unusual tiredness, weakness.
  • Hot flashes.
  • Decreased sex drive.
  • Nausea.
  • Trouble sleeping.
  • Acne or skin rash. (Low-dose OCs actually improve acne. Only Ortho Tri-Cyclen is approved for this.)
  • Depression, irritability, or other mood changes.
  • Swelling in the face, ankles, or feet.
  • Weight gain.

Newer formulations of combination pills that use low-dose estrogen and newer progestins may reduce and even avoid many of these side effects. Progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects. If side effects persist or are severe, a woman should always talk to her physician. Many women do not experience these side effects, or if they do, their bodies eventually adjust.

GnRH Agonists

Gonadotropin releasing hormone (GnRH) blocks the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel). Such agents may be used to alone or in preparation for procedures used to destroy the uterine lining. They are not generally suitable for long-term use.

Commonly reported side effects (which can be severe in some women) include menopausal-like symptoms that include hot flashes, night sweats, changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take them for more than six months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Osteoporosis
Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.
  • Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist.
  • Intermittent leuprolide, which uses repeated six-month courses of GnRH agonists followed by an average of nine months of symptom control only.
  • Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
  • Adding a bone-protective agent called a bisphosphonate (alendronate or etidronate) may also be helpful.
  • Other agents are being tested in combination with a GnRH agonist to preserve bone. They include parathyroid hormone or tibolone (available in Europe). Tibolone is known as a selective estrogen-receptor modulator (SERM), which means it has some, but not all, effects of estrogen.

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol

Danazol (Danocrine) is a synthetic substance that resembles a male hormone. It suppresses estrogen, and therefore menstruation, and is used (sometimes in combination with an oral contraceptive), to help prevent heavy bleeding. It may also improve operative success rates in women with menorrhagia when used before ablation or resection to destroy the uterine lining. It is not suitable for long-term use.

Adverse side effects include facial hair, deepening of the voice, weight gain, acne, and dandruff. It may also increase the risk for unhealthy cholesterol levels. Pregnant women or those trying to become pregnant should not take this drug because it may cause birth defects. [For more detail on this drug, see Well-Connected Report # 74, Endometriosis or Report #63, Fibroids.]

Agents Used for Women With Von Willebrand Disease and Other Bleeding Disorders

Desmopressin. Desmopressin is a drug that stimulates the release of blood factors that are particularly important for women with certain bleeding disorders, especially von Willebrand disease. High doses of a nasal spray containing desmopressin acetate, or DDAVP (Stimate) have reduced menorrhagia in women with bleeding disorders, including von Willebrand disease and mild hemophilia. Studies have been small, however, and it is not yet clear if the benefits are significant. Investigators are also studying its use for women with menorrhagia who have abnormally slow blood clotting but do not have an actual bleeding disorder. Side effects are mild to moderate. They include headache, nausea, and weakness.

Tranexamic acid. Tranexamic acid (Cyclokapron) is also useful for treating bleeding disorders. This is a synthetic form of the amino acid lysine and enhances blood clotting. (This agent is discussed above under Nonhormonal Agents.)

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