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Menstruation: Severe Cramps (Dysmenorrhea)

Description

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

Alternative Names

Cramps (Menstrual); Endometrial Ablation; Menstrual Disorders

Medications

A number of drugs are available to help relieve the symptoms of menstrual pain. None are cures, however, and a woman may need to take them during her entire reproductive life.

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 and also have other properties that act against 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. In fact, one 2001 study reported that overuse of NSAIDs for menstrual disorders contributed to iron deficiency anemia due to GI blood loss.

Stomach disease or trauma
An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. To avoid irritating an ulcer a person can try eliminating certain substances from their diet such as caffeine, alcohol, aspirin, and avoid smoking. Patients can take certain medicines to suppress the acid in the stomach causing the the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

COX-2 Inhibitors. Celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra) are known as COX-2 (cyclooxygenase-2) inhibitors, or coxibs. Meloxicam (Mobicox) is a related drug known as a COX-2 preferential. These agents are effective painkillers and are being studied with some success for dysmenorrhea. Studies on valdecoxib, for instance, reported fast action (within 30 minutes) with pain relief lasting up to 24 hours. COX-2 inhibitors have actions that are similar to those of NSAIDs, but studies suggest that they should be less harmful to the GI tract than standard NSAIDs. Still experts urge that studies are needed that are not sponsored by drug manufacturers in order to get a clear picture.

Acetaminophen. One study found 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, an agent used to reduce fluid build-up and bloating.) One study suggested that acetaminophen is less effective than NSAIDs for dysmenorrhea, but it 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.)

Hormone-based contraceptives Click the icon to see an image of hormone-based contraceptives.

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 on newer low-dose contraceptives using specific progestins have been promising. For example Yasmin contains a drospirenone, a progestin that resembles the natural form. Studies suggest that it helps reduce both dysmenorrhea and premenstrual symptoms. Mircette, which is a low-dose OC containing desogestrel, also has reduced menstrual pain. Other agents containing the progestin dienogest are showing promise but are not yet available in the US.

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 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) is proving to have important effects on menstrual disorders, regardless of its contraceptive effects. The LNG-IUS reduces pain in many women who suffer from dysmenorrhea. In one three-year study, the proportion of women with dysmenorrhea using the LNG-IUS dropped from 60% to about 30%. It is very helpful in reducing heavy bleeding and it may even help prevent endometriosis. One expert described the LNG-IUS as a nearly ideal contraceptive and some experts now believe it is a very good alternative to surgery for many women.

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 seven 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. (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. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually cause no symptoms and resolve on their own.

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.

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.

Hormonal Agents for Endometriosis

The basic approach in hormonal treatments for endometriosis is to block production of female hormones (estrogen and progesterone) or to prevent ovulation with other hormonal effects. Hormonal agents are used for pain relief only. None improve fertility rates and in some cases may delay conception. Specific hormonal agents may have different effects for women with endometriosis.

  • Inducing Pseudopregnancy: Oral contraceptives that contain estrogen and progestins mimic a pregnant state and block ovulation. (Progestins are natural or synthetic forms of progesterone). Progestins may also be used alone, since they have specific effects that can cause the endometrial tissue itself to atrophy.
  • Inducing Pseudomenopause: Gonadotropin-releasing hormone (GnRH) agonists or gestrinone, an anti-progesterone that mimic menopause. They reduce estrogen and progesterone to their lowest level.
  • Inducing On-going Blockage of Ovulation. Danazol, a derivative of male hormones, is a powerful ovulation blocker.

At this time, studies report that between 80% and 85% of women achieve pain relief after taking these agents. To date, comparison studies have found few differences in effectiveness among the major hormonal treatments. Differences occur mostly in their side effects. It should be noted that research on hormonal treatments for endometriosis is very scanty, and even physicians may not have the best data needed to make optimal decisions for their patients. Women should discuss the effects of particular medications with their physicians to determine the best choice.

Investigative Agents

Nitric Oxide Replacement. Nitric oxide relaxes smooth muscles and appears to inhibit uterine contractions. Studies have reported some early success for reducing menstrual pain using agents that are good sources of nitric oxide. They include skin patches containing nitroglycerin or glyceryl trinitrate. A 2002 study suggested, however, that a glyceryl trinitrate patch did not provide as much relief as a prescription NSAID. In addition, headache is a common and sometimes intolerable side effect. Still, more research is warranted.

Vasopressin Inhibitors. Vasopressin is a peptide produced in the hypothalamus in the brain that regulates blood volume by causing the kidneys to retain water and blood pressure by contracting smooth muscle in blood vessels. Drugs that block vasopressin, including atosiban and a similar compound SR 49059, are under investigation in Europe. Studies to date are promising but mixed on their effectiveness for dysmenorrhea.

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