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Menstrual disorders

Description

An in-depth report on the causes, treatment, and prevention of menstrual cramps.

Alternative Names

Dysmenorrhea; Menorrhagia; Amenorrhea; Cramps; Heavy menstrual bleeding

Medications

There are a number of different medicines prescribed for menstrual disorders.

Common Pain Relievers for Cramps

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that increase uterine contractions. They are effective painkillers that also help control the inflammatory factors that may be responsible for 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). In a comparison study of ibuprofen and naproxen, both were effective, but the effects of naproxen lasted longer. Naproxen, however, may carry a higher risk for gastrointestinal (GI) effects than ibuprofen. Long-term use of any NSAID can increase the risk for GI bleeding and ulcers.

Acetaminophen. Some evidence suggests that acetaminophen (Tylenol) reduces levels of female hormones (gonadotropins and estradiol, an estrogen), which may have some beneficial effect on menstrual disorders. A combination of acetaminophen and pamabrom (Women's Tylenol Menstrual Relief) is specifically aimed at treating menstrual pain and bloating. (Pamabrom is a diuretic, a drug used to reduce fluid build-up and bloating.) One study indicated that acetaminophen is less effective than NSAIDs for dysmenorrhea, but does not have the same potentially harmful effects on the gastrointestinal tract.

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). (Patch Contraceptives are now available in other forms, including patches and vaginal rings, but they may increase the risk for menstrual cramping.)

OCs are often used to regulate periods in women with menstrual disorders, including menorrhagia (heavy bleeding), dysmenorrhea (severe pain), and amenorrhea (absence of periods). Oral contraceptives are as effective for treating pain from endometriosis as the more potent gonadotropin releasing hormone agonists. They also protect against ovarian and endometrial cancers.

High-dose OCs have been specifically helpful for adolescents with severe dysmenorrhea. Studies with low-dose OCs are also showing promise in reducing menstrual pain for adolescents and adults. Some of the specific drugs used in these contraceptives are estradiol and levonorgestrel, drospirenone, and desogestrel.

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 (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 (Mircette, Necon, Nelova, Ortho-Novum). A 21-day pack consists of tablets of one strength and color taken for 7 or 10 days, then a second tablet with a different strength and color for the next 11 or 14 days. (A 28-day pack adds seven inactive tablets of a third color.)
• Triphasic regimen (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 5 to 7 days. For phase two, a second color and strength tablets is taken for 5 to 7 days. For phase three, a third color and strength tablet is taken for 5 to 10 days. The difference in duration of each phase depends on the brand. (A 28-day pack includes a fourth color inactive tablet for the last 7 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 drugs such as Seasonale, which contains estrogen and levonorgestrel. This approach produces a period only about every 3 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 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. However, a long-term study of 46,000 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 with irregular or skipped periods to restore regular cycles. Because of this, they may also help menstrual pain. They also reduce heavy bleeding and appear to protect against uterine and ovarian cancers. 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), may help treat menstrual disorders, regardless of its contraceptive effects. The LNG-IUS reduces heavy bleeding and pain in many women who suffer from menorrhagia and dysmenorrhea. In a 3-year study, the proportion of women with dysmenorrhea using the LNG-IUS dropped from 60% to about 30%. Some studies suggest that the LNG-IUS is more effective than oral contraceptives for controlling heavy menstrual bleeding.

Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). Studies report that about 60% of women with menorrhagia who use the LNG-IUS are able to avoid hysterectomy. Some clinical trials suggest that endometrial resection or ablation may be better at reducing menstrual bleeding than the LNG-IUS. Other studies report that the device is as effective as conservative surgery. Research also indicates that women who choose the LNG-IUS are as satisfied with their quality of life as those who choose surgery.

The Mirena is the current standard brand. FibroPlant is a unique "frameless" LNG-IUS device 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. The LNG-IUS releases progestin for up to 7 years. Progestin released by an IUD mainly effects the uterus and cervix and so it causes fewer widespread side effects than the progestin pills do. (However, the other major IUD--the Copper T--may increase bleeding.)

Irregular break-through bleeding can occur for the first 6 months, but afterward 80 - 90% reduction in blood loss has been reported. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually cause no symptoms and resolve on their own.

Injections (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. Women should not use Depo-Provera if they have a history of liver disease, blood clots, stroke, or cancer of the reproductive organs. [For more information, see In-Depth Report #91 : Contraceptives.]

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 2 to 3 months of oral contraceptive use, side effects from estrogen in the combined pill include: 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. Several studies have found no evidence that OC use increases the risk for breast cancer. Still, more research is needed. Estrogen has mixed effects on heart. It may improve cholesterol and other lipid levels. However, it also increases blood clotting and can increase the risk for stroke in certain women, especially smokers. 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. 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 substance, 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 (levonorgestrel, norethisterone). Third generation (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: Changes in uterine bleeding such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods. Patients should check with the doctor if any of these occur. Unexpected flow of breast milk Abdominal pain or cramps Diarrhea Fatigue, unusual tiredness, weakness Hot flashes Decreased sex drive Nausea Trouble sleeping Acne or skin rash (low-dose OCs may improve acne) 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 avoid many of these side effects. Progestins used in non-oral contraceptives, such as the LNG-IUS IUD, 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 doctor. Many women do not experience these side effects, or if they do, their bodies eventually adjust.

GnRH Agonists

Gonadotropin releasing hormone (GnRH) agonists are sometimes used to treat menorrhagia. GnRH agonists block 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 drugs may be used 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. These symptoms 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 these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

• 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 6-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 drug called a bisphosphonate (alendronate or etidronate) may be helpful.
• Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include parathyroid hormone or selective estrogen-receptor modulators (SERMs).

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 surgical 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 information on this drug, see In-Depth Report #74: Endometriosis or In-Depth Report #63: Uterine fibroids.]

• Review Date: 6/11/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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