The menstrual cycle involves the monthly preparation of the female genital tract for fertilization of an ovum and for implantation of the embryo into the lining of the uterus. Menstrual cycle changes are mediated by hormones—chemical messengers produced by the brain, the pituitary gland, and the ovary. The cyclic production of these hormones gives the menstrual cycle its periodicity, ie, the regular recurrence of the same events.

Although the menstrual cycle is a normal physiologic process, symptoms may occur that are distressing or uncomfortable. Up to 10% of reproductive-age women have severe perimenstrual symptoms (Logue and Moos, 1986). It is unusual for these symptoms to be a sign of serious illness, but if they interfere with daily activities or quality of life, intervention strategies can be considered.

The ovarian cycle

The ovary contains eggs (oocytes) as well as hormone-producing cells that govern menstrual cycle events and, in some cases, give rise to menstrual symptoms.

The goal of the ovarian cycle is the maturation of an oocyte and its release from the ovary at the optimum time for fertilization. When a girl reaches puberty, her ovaries contain about 200,000 oocytes. Each one is surrounded by ovarian stroma. The oocyte and surrounding layer of cells comprise a unit called the follicle. The primordial follicle is a resting phase; some follicles remain in this resting condition for decades.

During a woman's reproductive life, a select number of primordial follicles are recruited for further development. Stimulated by follicle stimulating hormone (FSH) produced by the pituitary gland, the oocyte matures and follicle cells proliferate. The primary follicle contains an oocyte surrounded by a single layer of specialized cells called follicle cells. In the next step, the secondary follicle has several layers of supporting cells, now called granulosa cells, surrounding the oocyte. The granulosa cells produce estrogen, a hormone with many functions including stimulating growth of the uterine lining, or endometrium, where the embryo will develop if pregnancy occurs. The endometrium will also give rise to menstrual bleeding if pregnancy does not occur.

In each cycle, a number of primordial follicles are recruited, but only one, as a rule, will ovulate. Some follicles stop developing at the secondary stage. The secondary follicles that continue to develop become antral follicles, having formed a fluid-filled space called an antrum. Typically, only one dominant antral follicle matures to a Graafian follicle, a structure with a large antrum that bulges from the surface of the ovary. The dominant follicle produces most of the estrogen that circulates in the woman's blood each month.

When the dominant follicle is fully mature, a pulse of luteinizing hormone (LH) is released from the pituitary, stimulating rupture of the follicle and release of the oocyte. The oocyte is picked up by the fallopian tube in which fertilization may occur. The remainder of the follicle is transformed into a corpus luteum. This structure now produces primarily progesterone, a hormone that modifies the endometrium, making it more suitable for implantation and for nourishment of the early embryo. If fertilization does not occur, the corpus luteum involutes after about 2 weeks. The resultant drop in progesterone results in bleeding from the endometrium.

The interplay of hormones responsible for the menstrual cycle is shown in Figure 2. This figure has been simplified to show only the hormones from the pituitary gland (FSH and LH) and the ovary (estrogen and progesterone). There are other factors that modify menstrual cycle hormones. Gonadotropin-releasing hormone (GnRH) is a short peptide produced by the hypothalamus at the base of the brain. GnRH stimulates production of FSH and LH by the pituitary. The release of GnRH is modified by many factors within the central nervous system, and in some women central nervous system factors such as stress can disrupt the menstrual cycle by influencing GnRH production.

The uterine cycle

The endometrium undergoes a cycle of growth and development in tandem with the ovarian cycle. The purpose of the endometrium is to provide protection and nourishment for the early embryo. After a menstrual period, the endometrium is reduced to its basal level. Before an embryo can implant successfully, the endometrium must regrow and become thicker. Stimulated by estrogen during the first half of the menstrual cycle, endometrial proliferation involves an increase in both the stroma, or connective tissue, and the blood vessels and glands of the endometrium.

After ovulation, the appearance of progesterone causes a change in the endometrium. Proliferation of the lining stops, the glands show an increase in secretions, and the arterioles become more tightly coiled. Endometrial gland secretions may play a role in nourishing the embryo prior to implantation, when the embryo is free within the uterine cavity. The coiling of the arterioles is important in limiting menstrual bleeding if fertilization does not occur. The muscle walls of the arterioles constrict when progesterone levels fall, and this constriction results in ischemia of the endometrium. In response to this ischemic necrosis, the endometrium falls apart, resulting in shedding of the lining as the menses. Because the arterioles are constricted, blood loss during the shedding process is usually only about 60 mL, although there are large variations among women.

Clinical landmarks of the cycle

The physiologic events of the menstrual cycle can produce signs and symptoms readily identifiable by the woman. Estrogen not only results in growth of the endometrium but also in proliferation and swelling of the duct system in the breast, causing some women to experience an increase in breast size or sensitivity as the cycle progresses. Progesterone can also can produce proliferation of breast glandular tissue, so the second half of the cycle can also be marked by breast enlargement, tenderness, or lumpiness. Estrogen causes the cervix to produce copious clear mucus; just prior to ovulation, when estrogen levels are high, women may note an abundant clear discharge. This cervical mucus protects sperm deposited in the vagina, and it makes sense that the mucus is the most abundant just prior to ovulation, when it is most desirable to have viable sperm in the female genital tract.

Some women experience symptoms around the time of ovulation. Ovulatory pain, which is felt in one or the other lower abdominal quadrants, may be caused by release of blood or fluid when the dominant follicle ruptures. The decrease in estrogen around the time of ovulation may also trigger a small amount of spotting or bleeding from the uterus.

The most notable attribute of the reproductive cycle is the menstrual discharge. The occurrence of regular menstrual bleeding is a reliable clinical indicator that ovulation has occurred and that the woman is ovulatory. Women who do not ovulate will not produce progesterone and will not have tightly coiled arterioles in the endometrium. These women will bleed when the endometrium proliferates excessively and falls apart because it is too thick. This kind of bleeding occurs at irregular intervals, and because the arterioles are not coiled, this so-called anovulatory bleeding can be heavy and prolonged.

Changes in progesterone, estrogen, and perhaps other hormones of the second half of the cycle can cause other symptoms prior to menstruation, such as alterations in mood and skin appearance. Women who have premenstrual symptoms and regular menses are almost certainly ovulatory. Most ovulatory women, in fact, have premenstrual symptoms that tell them a menstrual period is coming before a discharge occurs.

In some cases, premenstrual symptoms are severe and unpleasant. When these symptoms interfere with normal activities or require medical attention, they are called premenstrual syndrome, or PMS. There is no clear demarcation between “normal” premenstrual symptoms and PMS. Designating the woman's condition as PMS occurs when the symptoms cause enough distress that attention is required. Similarly, symptoms that occur during the menstrual period itself may be distressing, and there is no clear demarcation between normal and abnormal menstrual symptoms. Finally, it is common for some menstrual symptoms to begin prior to the appearance of menstrual bleeding, and there may be nodistinction between a woman's premenstrual symptoms and her menstrual symptoms. Therefore, the consideration of menstrual symptoms necessarily overlaps to some extent the consideration of premenstrual symptoms.


Heavy or prolonged bleeding (Menorrhagia)

Heavy menstrual bleeding, also called menorrhagia, is sometimes defined as greater than 80 mL blood loss during a menstrual period. Of course, women do not measure their menstrual blood loss, so the clinical definition of this problem is more subjective. Certainly, if a woman has anemia attributable to menstrual blood loss, it can be argued that she deserves treatment for heavy bleeding whether or not it bothers her. Prolonged menstrual bleeding is less subjective, being defined as bleeding in excess of 7 days per cycle; however, some women are accustomed to shorter bleeding durations and may seek treatment if their menses duration increases, say, from 3 to 6 days.

In addition, women with heavy menstrual periods commonly complain of passing blood clots, which can be a frightening occurrence, particularly if new in onset. All blood will clot, and it is not unusual for menstrual blood to clot within the uterus. The clot can dissolve within the uterus, and be liquid again when it passes from the vagina. Also, typical menstrual discharge contains tissue fluid and endometrium as well as blood, and these nonblood components do not clot. When bleeding is heavy or brisk, the clot within the uterus may come out before it has dissolved, and there may be less tissue fluid and endometrial components in the menstrual discharge. The appearance of clots, then, is simply a marker of heavier, more rapid blood loss, rather than having another, more sinister significance.

The cause of heavy or prolonged menstrual bleeding is usually unknown; however, some women have diseases that can be associated with bleeding abnormalities. Coagulation disorders, such as von Willebrand's disease, will sometimes come to attention for the first time when a girl begins to menstruate and the periods are unusually heavy. Diagnosis of a coagulation abnormality requires special laboratory testing.

Other women with heavy or prolonged bleeding have abnormalities of the lining or the muscle wall of the uterus. Uterine fibroids (leiomyomata uteri) are benign smooth muscle tumors of the uterine wall that can distort the endometrial cavity and be associated with abnormally heavy menstrual bleeding. Polyps, which are fingerlike growths in the endometrial cavity, can also be associated with heavy bleeding. Polyps are usually benign, but occasionally contain a cancer. Based on pelvic examination, uterine fibroids can be suspected if there is enlargement or irregularity of the uterus. Ultrasound examination (sonography) is often used to identify fibroids and to evaluate their relationship to the endometrial cavity. Polyps may also be identified on ultrasound, although they are often smaller and more difficult to visualize than fibroids. Both fibroids and polyps involving the endometrial cavity can be identified (and in many cases removed) by hysteroscopy, a minor surgical procedure in which a telescope is inserted into the uterus through the cervical canal.

Endometriosis, which occurs when endometrial tissue grows outside of the endometrial cavity, can be associated with heavy menstrual bleeding, although the mechanism by which endometriosis produces this symptom is not known. Adenomyosis, which occurs when endometriosis involves the muscle wall of the uterus, is also associated with heavy menstrual bleeding. Endometriosis can be visualized in some instances by looking inside the peritoneal cavity with a laparoscope. Adenomyosis can be diagnosed using magnetic resonance imaging (MRI) of the uterus. It is uncommon, however, for laparoscopy or MRI to be used routinely in the evaluation of heavy menstrual bleeding because hormonal therapy, which is the mainstay of treatment of endometriosis and adenomyosis, is also used for treatment of heavy menstrual bleeding of unknown cause. Hormonal therapy will be discussed in more detail later in this monograph.

In most cases, abnormally heavy bleeding or prolonged menses is assumed to be due to excessive proliferation of the endometrium or inadequate coiling of the spiral arterioles. Both of these situations might prevail if progesterone production by the c orpus luteum were inadequate to produce arteriolar changes and to stop endometrial proliferation. Deficient function of the corpus luteum is believed to occur more frequently as women age, and episodes of heavy menstrual bleeding can often take place in the years prior to menopause.

Prostaglandins may also play a role in regulating menstrual bleeding. Prostaglandin I2 (prostacyclin) is a vasodilator produced by the endothelial cells of blood vessels. Thromboxane is a vasoconstricting prostaglandin produced by platelets. Having an appropriate amount of menstrual bleeding may require the right balance between these two prostaglandins and perhaps other agents in this class; abnormalities of prostaglandin availability may be involved in the production of abnormally heavy menses.

A distinction should be made between heavy or prolonged periods and irregular bleeding. Irregular bleeding implies the lack of a cycle; in other words, a woman may bleed for 4 days, stop for 2 or 3 days, bleed again for a day or two, and so on. This so-called “lawless” bleeding can occur when a woman does not ovulate at all. Under these conditions, the endometrium proliferates without the countervailing influence of progesterone. When the endometrium becomes sufficiently thick, it falls apart, and bleeding from the arterioles may start and stop. Another anovulatory bleeding pattern is a heavy prolonged episode of bleeding every 2 or 3 months, when the thickened endometrium falls apart and is discharged in large amounts in one episode, albeit lasting many days or even weeks. Anovulatory bleeding episodes are not true menstrual periods, because menstrual periods imply the regular shedding of the endometrium in an ovulatory cycle. Anovulatory bleeding is a warning sign of possible endometrial hyperplasia or cancer, conditions that are due to prolonged stimulation of the endometrium by estrogen without adequate protection from progesterone. The evaluation and treatment of anovulatory bleeding will not be considered here; suffice it to say that a history of irregular bleeding is best evaluated by examination by a gynecologic practitioner and in some cases by more invasive testing.

Painful periods (Dysmenorrhea)

Menstrual cramps are extremely common, and most women have developed their own methods for dealing with this kind of discomfort. Some women, however, have menstrual pain that is difficult to control and that may interfere with daily functioning. Dysmenorrhea is the term used for painful periods.

Most menstrual pain is believed to originate in the uterus, mediated by prostaglandins, particularly by prostaglandin F2alpha, released by degenerating endometrial cells (Coco, 1999; Deligeoroglou, 2000). The prostaglandins induce uterine muscle contraction and ischemia.

In some cases, menstrual pain originates outside the uterus. Endometriosis is a common cause of menstrual pain, and pain from lesions of endometriosis can originate from wherever the disease is implanted. At one time, it was believed that endometriosis caused pain because endometrial implants bleed during the menstrual cycle in response to hormonal changes that normally occur. Because the endometriosis implants are in tissues where they don't belong, the abnormally located menstrual blood was believed to produce irritation and pain. Although this theory is not implausible, and may describe pain production in some women with endometriosis, there are other women in whom painful endometriosis exists without evidence of bleeding from the abnormally located tissue. In addition, endometriosis pain can occur between, as well as during, menstrual periods.

Other causes of pain, which may not be gynecologic in origin, can be present in women with menstrual pain. These other painful conditions may show cyclic variation, and may worsen with the menstrual period. For example, irritable bowel syndrome may be more symptomatic during menstrual periods than between them, and some women with irritable bowel syndrome have symptoms only during their menstrual periods. Other painful conditions, such as fibromyalgia and interstitial cystitis, may also produce more symptoms during the menses.

Bloating and breast changes

A sensation of fullness or bloating may be prominent prior to or during menstruation. The sensation may be associated with weight gain caused by fluid retention. Fluid retention results from the mineralocorticoid activity of some of the hormones that increase in the second half of the menstrual cycle. At one time, the mineralocorticoid activity was blamed on progesterone. Figure 4 shows why this belief was held. In the synthesis of steroids by the adrenal gland, progesterone can be a precursor of aldosterone, the major mineralocorticoid hormone in the body. Aldosterone secretion results in the retention of sodium and water by the kidney. It was natural to assume that progesterone produced by the corpus luteum would also be metabolized to aldosterone; however, progesterone produced by the corpus luteum is largely metabolized by different pathways and does not get transformed into mineralocorticoids.

Progesterone, in fact, has antimineralocorticoid activity, antagonizing the action of natural aldosterone (Landau et al, 1955; Landau and Lugibihl, 1958, 1961). This antagonism appears to be at the level of the aldosterone receptor. During the luteal phase of the cycle, perhaps in response to the progesterone antagonism, plasma levels of aldosterone increase (Michelakis et al, 1975; Katz and Romfh, 1972). As progesterone levels decline in the premenstrual days, this anti-aldosterone effect of progesterone is withdrawn, and sodium and fluid retention can occur. Some women will gain 5 lbs just before or during the menstrual period, losing the weight rapidly after it is over.

Breast enlargement and tenderness around the time of the menstrual period may be due to fluid retention, but may also be the result of changes in breast tissue associated with estrogen and progesterone. As indicated above, estrogen stimulates growth of the ductal elements of the breast, ie, the system of small tubes that carry milk from the milk-producing glands to the nipple during lactation. Progesterone stimulates growth of the glandular elements themselves, and that process is associated with an increase in fluid within the breast tissue. The net effect is that breast tissue becomes more prominent, lobular, and, in some cases, tender.

Bloating and breast discomfort are self-limited symptoms without serious medical consequences, but they are the menstrual cycle effects that women complain about most frequently (Pullon et al, 1987).

Mood changes

The brain is a hormonally responsive organ, and changes in behavior and mood over the course of the menstrual cycle have been documented (Krug et al, 1996). Most investigators have associated the time around ovulation with an increase in creativity, flexibility, and sexual interest. It has been postulated that these mental changes make it more likely that women will respond to or initiate sexual advances, increasing the likelihood of pregnancy during this fertile time.

These periovulatory changes are subtle, and can be identified only by sophisticated psychological testing. On the other hand, many women report negative mood changes around the time of menstrual bleeding, including depression, anxiety, social withdrawal, hostility, and irritability. The severity of these negative symptoms varies from one woman to the next; some barely notice a change while others become suicidal or homicidal.

Menstrual-associated mood problems have been given different names over the years. Sometimes called premenstrual tension, these negative mood symptoms have been gathered together with physical symptoms such as breast tenderness and bloating under the designation of premenstrual syndrome (PMS). More recently, the mood disturbance associated with PMS has been called late luteal phase dysphoric disorder (LLPDD) or menstrual cycle-related mood disorder (MRMD) or premenstrual dysphoric disorder (PMDD).

Some investigators have regarded PMS with its associated mood disturbances as a condition that always ends with the onset of menses. It is clear, however, that there are different patterns in different women, with some experiencing symptoms that extend well into the days of menstrual bleeding (Mortola, 1992).

Up to 40% of reproductive-age women can be diagnosed with PMS, but the incidence of the problem varies with the way the diagnosis is made (Chihal, 1990). Some have favored a strict definition of PMS, requiring prospective charting of symptoms over several months in order to document the cyclic nature of the complaint. It has been determined, for example, that women are unreliable in deciding on their own if they have PMS, and it has been said that half of women who diagnose themselves with PMS are mistaken (Chihal, 1990). This point of view may be scientifically defensible, but it raises the question of what to do about a woman who complains of troubling mood problems around her period, but does not satisfy formal criteria for PMS. This woman surely deserves attention, regardless of whether or not a formal label can be applied to her symptoms.

One problem in making a diagnosis is that women who have psychiatric diseases, such as anxiety disorders or depression, may experience substantial changes in their symptoms at different parts of their cycle (Mortola, 1992). A woman with depression may only report a problem right before and during her menstrual period, but on closer questioning she may never feel normal, even on her so-called good days. In other words, instead of going from feeling well to feeling depressed, as a woman with strictly defined PMS does, she may go from feeling depressed to feeling horribly depressed.

What causes mood to change with the menstrual cycle in some women? At one time it was thought that women with cycle-related mood disorders had abnormal levels of hormones, and there was a period when supplementing menstrual cycle hormones such as progesterone was believed to be effective. It is clear that women with cycle-related mood disorders do not differ in estrogen and progesterone levels from those without these mood disorders (Rubinow and Schmidt, 1995). There are some differences in the response of the pituitary gland to thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) in women who have cyclic mood disorders and those who don't, but it is not clear that these differences are clinically important.

It appears more likely that alterations in central neurotransmitters cause cyclic mood problems. A leading contender for the central nervous system transmitter responsible for menstrual mood problems is serotonin, which also plays a role in depression (Rapkin, 1992). Other neurotransmitter chemicals are also likely to be involved. In experimental animals and women, serotonin metabolism is affected by ovarian hormones, and in some women, the cycle-associated alterations in the serotonin economy may be sufficient to result in mood disturbance.

Skin changes

It is common for women to experience an increase in oiliness of the skin and hair and an increase in acne just prior to or during the menstrual period. Some women can tell their menstrual period is about to begin based on changes in their complexion.

Oily skin and acne reflect an increase in sebaceous gland activity. The sebaceous glands lubricate the skin and hair. In acne, there is obstruction of the gland ducts. The fatty sebaceous contents of the glands become colonized with microorganisms, and the sebaceous gland contents become irritating to the surrounding skin.

Sebaceous gland activity is increased by androgens (male hormones), but the blood levels of androgens in women do not increase around the menstrual period (Steinkampf, 1990). The explanation for the greater sebaceous activity around the menstrual period may lie not with the level of androgens but with the counterbalancing estrogens, which are particularly low just before and during the menstrual period.


Many women with menstrual discomforts have learned ways of making themselves feel better during this time of the month; however, many others continue to suffer and would benefit from advice on how to manage their symptoms. It is common for women to use nonspecific methods, such as bed rest, heat, and distraction, which they have learned from their mothers or from friends (Campbell and McGrath, 1999). While some women receive benefit from such measures, these methods are often not associated with substantial symptom relief by most women. A variety of more effective treatments are available; none will be suitable for all women, but most women can expect to gain relief from some combination of available treatments.

The therapies discussed here include only nonsurgical options. Surgical therapies are available for women who have not responded to nonsurgical treatments. These therapies generally involve removal of the ovaries or the uterus or destruction of the endometrium.

Nonpharmacologic Therapies

Diet—The relationship between diet and menses-related symptoms is not very clear. Some women believe that avoiding salt during the latter part of their cycles reduces bloating or mastalgia, although no studies have confirmed this theory.

The effect of a low-fat diet on dysmenorrhea and water retention was tested in a crossover study of 33 women, of whom 21 completed the trial (Barnard, 2000). Women were assigned to a low-fat vegetarian diet or their regular diet plus a placebo pill; after 2 months the women crossed over to the other regimen. The duration of dysmenorrhea was significantly decreased by the diet from 3.9 to 2.7 days. The duration of symptoms attributable to water retention decreased significantly from 2.9 to 1.3 days. The placebo treatment had no effect. Another study also found a decrease in symptoms associated with water retention during the premenstrual week and during menses in women given a low-fat diet (Jones, 1987).

The type of fat consumed may also make a difference in dysmenorrhea. Fish oil, high in omega-3 fatty acids, modulates prostaglandin production and may have an effect on menstrual cramps. A Danish survey of 181 women 20 to 45 years of age utilized food-intake diaries and found that menstrual pain was significantly correlated with a low intake of animal and fish products and a low omega-3 to omega-6 dietary ratio (Deutch, 1995).

In a crossover study, 42 adolescents with dysmenorrhea were randomized to placebo or fish oil supplements (eicosapentaenoic acid 1080 mg, docosahexaenoic acid 720 mg, and vitamin E 1.5 mg); after 2 months the groups were crossed over. As assessed by the Cox Menstrual Symptom scale, dysmenorrhea symptom scores decreased significantly (from 69.9 to 44.0) after fish oil treatment; there was no difference between placebo and baseline (Harel, 1996).

Exercise—A review of studies on dysmenorrhea and exercise identified seven trials on the subject (three observational studies and four randomized controlled trials) (Golomb, 1998). All of the randomized controlled trials (two of which compared different types of exercise and two compared exercise to no exercise) found a reduction in dysmenorrhea. Two observational studies found a lower prevalence of dysmenorrhea in regular exercisers; the third (which adjusted scores for disposition, medication, stress, and mood) found that regular exercisers had more menstrual symptoms than nonexercisers.

A randomized controlled trial compared the effects of an hour of aerobic exercise three times per week or of strength training on premenstrual symptoms in 23 healthy women (Steege, 1993). While participation in either type of exercise improved many premenstrual symptoms, the only significant difference between groups was in premenstrual depression, which was less in the aerobic exercise group. Compared to baseline, the aerobic exercise group improved in various measures of mood, while the strength-training group improved in food cravings and in feelings of bloating or abdominal heaviness.

A survey among 2912 women on US Navy ships gathered information on weight, height, cigarette smoking, alcohol consumption, exercise, and menses-related symptoms (including cramps, intermenstrual bleeding, excessive menstrual frequency, heavy menses, menstrual bleeding longer than a week, and irregular periods) (Kritz-Silverstein, 1999). Current cigarette smoking was associated with increased risk of all menstrual symptoms and cycle disorders. Exercise, obesity, and alcohol consumption were not consistently related with either menstrual symptoms or cycle disorders.

TENS - Transcutaneous electrical nerve stimulation—Transcutaneous electrical nerve stimulation (TENS) has become an accepted treatment for various kinds of pain, and while it is not commonly used for this purpose, there is evidence that TENS is effective for dysmenorrhea. In a randomized crossover study, 32 women with severe primary dysmenorrhea were treated with TENS for two cycles, sham TENS (ie, the “placebo” control) for one cycle, and ibuprofen for one cycle (Dawood, 1990). During the TENS and placebo TENS cycles, ibuprofen 400 mg (up to 1600 mg/day) was allowed. Subjects receiving TENS did not require ibuprofen or required less ibuprofen than with the two other treatments. TENS also significantly reduced diarrhea, menstrual flow, clot formation, and fatigue compared with placebo TENS.

An open, randomized crossover study in 12 women compared the use of TENS stimulation and oral naproxen (500 mg) on dysmenorrhea and intrauterine pressure (Milsom, 1994). Pain scores were significantly reduced within 30 to 60 minutes following treatment with TENS and within 19 to 120 minutes after naproxen administration.

Acupuncture—Acupuncture, the insertion of fine needles into specific points along nonanatomic energy meridians in an effort to balance energy, is part of traditional Chinese medicine. One study of dysmenorrhea compared two acupuncture groups with two control groups. Eleven women received acupuncture at real acupuncture points, 11 received placebo acupuncture at nonacupuncture points, 10 women continued prior treatment (standard controls), and 11 continued prior methods but also received extra office visits (visit control) (Helms, 1987). Both acupuncture groups were treated for 3 weeks of each month (every week except during menses) for three menstrual cycles. The proportion of women whose average pain scores were reduced by one-half after treatment was significantly higher in the real acupuncture group compared to each of the other groups.

Chiropractic—Chiropractic uses manual techniques to adjust spinal vertebrae. While this treatment is more accepted for back pain or musculoskeletal disorders, it is also used to treat excessive bleeding or dysmenorrhea. A small dysmenorrhea trial compared chiropractic manipulation (at least twice a week) in eight women with three controls (Thomason,1979). Seven of the eight women treated with chiropractic experienced decreased pain and disability, compared with none of the controls.

In a randomized controlled trial of 45 women with dysmenorrhea, 24 women received spinal manipulative therapy and 21 women received sham manipulation (Kokjohn, 1992). The spinal manipulation group had less abdominal pain than the sham-treated group and lower scores on a menstrual distress questionnaire.


Herbs—Asian herbal medicine is popular for gynecological conditions, including menorrhagia or dysmenorrhea. Manufacturing processes may not be inspected, however, and the quality of herbal products may not be uniform. A case of lead poisoning from an Asian remedy for menstrual cramps (Koo Sar or Koo So pills) was reported in Connecticut in 1997 (MMWR, 1997). In spite of clinician concerns about quality control, these products remain popular among women for the self-treatment of menstrual discomforts.

Oil from the seeds of evening primrose is high in gamma-linolenic acid. Black currant seed and borage seed oil are used interchangeably. EPO is a popular treatment for several gynecological conditions, including mastalgia. A Welsh case series of 414 patients with either cyclic or noncyclic breast pain found that EPO 3 g daily equaled bromocriptine in effectiveness, although it was not as effective as danazol (Gately, 1992). Thirty percent of the danazol group and 35% of the bromocriptine group reported significant adverse events, compared to 4% of the EPO group. However, a randomized, double-blind, placebo-controlled crossover trial of EPO in 27 women with premenstrual syndrome and 22 asymptomatic controls did not support this effect. The effect of evening primrose oil (12 capsules of Efamol, containing 4.32 g linoleic acid and 0.54 g gamma-linolenic acid) was tested on breast swelling and discomfort as well as happiness and feelings of well-being; depressed feelings and crying spells; irritability and short temper; headache; fatigue; sexual need and positive feelings toward sex; energetic feeling; and tension and anxiety. Each treatment was given for four cycles. Although symptoms in both groups improved over time, EPO had no beneficial effect over placebo (Collins et al, 1993). A systematic review of seven placebo-controlled trials of EPO for PMS identified only one other trial besides Collins that was properly randomized and well controlled. This trial of 38 subjects with at least one symptom of fluid retention and breast discomfort and two symptoms of mood changes tested eight capsules Efamol daily; there was no benefit for EPO over placebo (Budeiri, 1996).

St. John's wort is a popular antidepressant herb. In one study, 19 women took one 300 mg tablet containing 900 µg hypericin daily for two complete menstrual cycles (Stevinson, 2000). There were significant improvements in mood, including anxiety, irritability, depression, and mood swings; there was also a significant decrease in tender breasts and in complaints of swelling. The dose of St. John's wort used in this study is one third of the usual dose for depression. St. John's wort can cause photosensitivity and interacts with numerous drugs.

Chaste-tree berry is an herb used to treat various gynecologic conditions. An open study of 1634 patients in Germany with PMS tested the effect of this herb on several symptoms including mastalgia (Loch, 2000). Compared to baseline, subjects experienced a significant decrease in pain, tenderness, tension, bloating, and swelling.

Vitamins and minerals

Some alternative medicine practitioners and consumers believe that vitamin E balances hormone levels and use it for a variety of conditions, including mastalgia. There is no reasonable evidence to support this claim. A randomized double-blind study compared d-alpha tocopherol (400 IU) for three cycles in 46 women (41 completed) on various premenstrual symptoms (London, 1987). Although a favorable result was claimed, no significant difference was seen between groups.

Vitamin B6 does not appear to be helpful in treating mastalgia. A controlled trial of 32 women with mastalgia tested the effects of vitamin B6 500 mg/day for 4 months. The outcome measure was improvement or worsening of mastalgia. Almost 60% of subjects in each group improved; there was no difference between groups (Wyatt et al, 1999).

Another controlled crossover study of 42 hospital patients with severe cyclical mastalgia tested the effects of vitamin B6 200 mg/day against placebo, each for two cycles. Acetaminophen was allowed. Subjects were assessed monthly; breast pain and tenderness were rated on a visual analog scale and chart, and acetaminophen requirement was recorded. No significant difference was seen between groups on any measures (Smallwood, 1986).

Another crossover trial of 32 women with premenstrual symptoms tested the effects of placebo against vitamin B6 50 mg/day on emotional, somatic, and menstrual symptoms. Each treatment was given for three cycles (with one washout cycle in between). There was a beneficial effect of vitamin B6 on depression, irritability, and tiredness, but not swelling, breast discomfort, cramps, or backache (Doll, 1989). High doses of vitamin B6 can cause neurological symptoms; sensory neuropathy has been reported in patients taking more than 2000 mg of B6 daily, but rarely with lower doses (Jacobson et al, 1996).

A randomized, double blind, placebo-controlled crossover study tested the effect of calcium on menstrual and premenstrual symptoms (Thys-Jacobs, 1989). Calcium carbonate (1000 mg/day elemental calcium) was tested in 33 women for three cycles. Calcium treatment for three cycles significantly reduced abdominal cramps and back pain.

A larger randomized double-blind, placebo-controlled multicenter trial assessed calcium carbonate (600 mg/day elemental calcium) in 497 healthy premenopausal women with moderate to severe premenstrual symptoms (Thys-Jacobs, 1998). After three menstrual cycles, the calcium group experienced a significant improvement in mood swings, depression, tension, anxiety, and anger. Improvement was also noted in swelling of extremities, breast tenderness, abdominal bloating, headache, fatigue, food cravings, and pain, including lower abdominal pain, generalized aches, and low backache.

Magnesium has been used for cycle-related mood changes. A double blind, randomized trial of magnesium 360 mg three times/day during the second half of the cycle found that magnesium significantly reduced menstrual symptoms (Facchinetti, 1991). Another randomized double blind, placebo-controlled crossover study compared the effect of 200 mg/day magnesium with placebo on premenstrual symptoms in 38 women for two menstrual cycles (Walker, 1998). In the second month, there were significant improvements in swelling, weight gain, breast tenderness, and abdominal bloating.

NSAIDs - Nonsteroidal anti-inflammatory drugs —Medications that inhibit prostaglandin synthesis are known as nonsteroidal anti-inflammatory drugs (NSAIDs). Many NSAIDs are inhibitors of the enzyme cyclooxygenase (COX). There are two isoforms of this enzyme, COX-1 and COX-2. Most NSAIDs currently available inhibit both forms of the enzyme. Because COX-1 inhibition is involved in gastrointestinal and renal toxicity, selective inhibitors of COX-2 are available for people who cannot tolerate the nonspecific NSAIDs. COX-2 inhibitors are more costly than nonspecific NSAIDs and do not appear to be more effective in pain relief than the nonspecific NSAIDs.

NSAIDs are useful in reducing the pain of dysmenorrhea. Pain relief from NSAIDs can be due to the analgesic effects of these agents, but is also likely to result from inhibition of prostaglandin synthesis within the uterus. The effectiveness of NSAIDs in dysmenorrhea depends on the use of adequate doses of these agents (Hersh et al, 2000). It is also useful to administer NSAIDs in anticipation of the pain, prior to synthesis of prostaglandins, as opposed to administering them only after pain is intense and the bulk of the uterine prostaglandins have already been synthesized. Table 1 lists some NSAIDs that are sold without a prescription and prescription-level doses that will be useful for dysmenorrhea.

NSAIDs can also be useful for excessively heavy menstrual periods and have been shown to reduce menstrual blood loss by 30% (Anderson et al, 1976). As in pain relief, use of these medications prior to the onset of heavy bleeding is more likely to be effective than use after heavy bleeding has started.

Diuretics and agents for mastalgia—Because bloating and mastalgia are prominent symptoms associated with menses, many nonprescription remedies for menstrual discomfort contain diuretics. Pamabrom, for example, is a mild diuretic that is a component of a popular nonprescription remedy for menstrual discomfort. Other menstrual discomfort medicines contain caffeine, which also has diuretic properties.

When a prescription diuretic is used, some clinicians prefer spironolactone at doses of 25 to 200 mg/d (Johnson, 1992). Spironolactone is favored because it is potassium sparing and is associated with less rebound edema than thiazide diuretics (ACOG, 2000). The preference for spironolactone may also reflect the underlying increase in aldosterone that occurs around the time of the menstrual period. As discussed above, this increase in aldosterone is a response to the anti-aldosterone effects of progesterone.

Although use of diuretics may be sufficient to relieve breast pain, other medications with activity on the breast have been used. Bromocriptine, tamoxifen, and danazol have been used for cyclic mastalgia (Blichert-Toft et al, 1979; Fentiman et al, 1985; Watts et al, 1987). Although these medications have been shown to be effective in small studies, they have not been much more effective than placebo, and their use has been limited by side effects. Bromocriptine is associated with dizziness and nausea, tamoxifen can produce hot flashes, and danazol may produce androgenic effects such as oily skin, acne, and bloating.

Psychiatric medications—Mood disturbances can be among the most disabling of the symptoms associated with the menstrual cycle. Although women with mood symptoms before and during menses have been considered by some writers to be highly responsive to placebo, formal investigations show that only a minority (20%) have a meaningful or sustained improvement with placebo treatment (Freeman and Rickels, 1999). Some of the medications that have been used for these mood disorders are listed in Table 2.

The anxiety and irritability associated with the menstrual period can be treated with benzodiazepines or with buspirone (Severino and Moline, 1995; Brown et al, 1998). Benzodiazepines are often recommended for episodic use, ie, to be taken only when symptoms occur for a few days each month. There is concern that habitual use of benzodiazepines may result in dependence and in a withdrawal syndrome with abrupt discontinuation. Buspirone is a nonbenzodiazepine anxiolytic with which some practitioners have a greater degree of comfort if frequent or regular use is likely.

Episodic use of anxiolytic medications—only on those days when symptoms occur—offers the opportunity to abort uncomfortable symptoms without long-term use of pharmacologic agents. Some women with menstrual-associated mood problems prefer this kind of therapy because it is not associated in their minds with the stigma of long-term use of psychiatric medication.

A number of antidepressant medications have been used for cyclic mood disorders (Table 2). There appears to be consensus that serotonin-dominant agents are more effective than noradrenergic-dominant agents, although controlled comparisons are few in number (Severino and Moline, 1995; Brown et al, 1998). There have been reports of women using antidepressant medications only during the second half of the menstrual cycle, with good effect on menstrual-associated mood disturbance, but most of these agents are used daily. Some women may therefore decide that the number of days each month that they have symptoms is too few to warrant daily use of antidepressant medication.

Oral contraceptives—Oral contraceptives are among the most commonly prescribed medications for menstrual discomforts. Many of the medications discussed above deal with the symptoms produced in response to the ovarian hormones. Oral contraceptives address some of these symptoms, but also suppress normal ovarian hormone production, replacing it with the oral contraceptive hormones.

Combination oral contraceptives in use today contain an estrogen and a progestin. Nearly all oral contraceptives contain ethinyl estradiol as the estrogen. This estrogen is similar to naturally occurring estradiol produced by the follicle, but the ethinyl group protects the molecule from degradation in the gastrointestinal tract. Women on ethinyl estradiol tablets not only are exposed to a potent estrogen but also experience high estrogen levels in the portal circulation, which goes from the gastrointestinal tract where the tablets are absorbed, directly to the liver. The estrogenic activity in the portal circulation results in an increase in hepatic protein synthesis. Among these hepatic proteins are angiotensinogen, resulting in an increase in activity of the renin-aldosterone system (Oelkers, 1996). In the United States, oral contraceptives in widespread use contain 20 to 35 mg ethinyl estradiol, usually given for 21 days of every 28-day cycle. Although some products contain different estrogen doses at different parts of the cycle, most contain a level dose during the 21 days of steroid administration.

Oral contraceptives also contain progestins. The progestin in the pill prevents excessive proliferation of the endometrium and often produces substantial endometrial atrophy, giving rise to light and short menstrual bleeding in many women. A number of different progestins exist. Nearly all of them are derivatives of testosterone, with a variety of modifications to decrease the androgenicity of the preparation. One progestin, drospirenone, is a spironolactone analogue, with antimineralocorticoid and antiandrogenic effects (Muhn et al, 1995; Fuhrmann et al, 1996).

Because the estrogenic component of most oral contraceptives is the same, there has been considerable effort to modify the progestin component to optimize oral contraceptive effects. The older progestins (eg, norethindrone, norgestrel) have considerable androgenic activity in and of themselves, although administration with the potent estrogen in the oral contraceptive preparation does not result in androgenic problems such as oily skin, acne, or lipid abnormalities in most women. Newer progestins (eg, gestodene, norgestimate, desogestrel) are largely devoid of androgenic effects, and an oral contraceptive preparation containing one of these progestins has been approved for the treatment of acne. It is an interesting side note that the effect of oral contraceptives on acne may be due to an estrogen-mediated increase in sex hormone-binding globulin (SHBG), a hepatic protein whose production is increased by oral estrogens. With increased SHBG levels, there is more binding of the woman's endogenous testosterone and less free testosterone. This effect would be expected to have a benefit for acne, irrespective of the progestin associated with the estrogen. Whether oral contraceptives containing gestodene, desogestrel, or norgestimate work better for acne than oral contraceptives containing the same estrogen with an androgenic progestin is not known.

As different products were developed in the past, there was enthusiasm for changing the progestin dose throughout the 21 steroid-containing days of the cycle. The so-called multiphasic tablets contained generally the same dose of estrogen with two or three different doses of progestin as the cycle went on. Manufacturers of the multiphasic preparations offered a number of reasons why multiphasic preparations would be better than monophasic forms, but no advantage in contraceptive effectiveness, health endpoints, or side effects has been demonstrated among these products in controlled studies. There appears to be no scientific reason to prefer a multiphasic product to a monophasic one.

The use of oral contraceptives for menstrual complaints is based on the following observations:

(1) Menstrual periods on oral contraceptives are often lighter and shorter than menstrual periods off oral contraceptives. These agents appear to work by inducing endometrial atrophy (a progestin effect) and by decreasing uterine prostaglandin production.

(2) Endogenous estrogen and progesterone production are suppressed, possibly leading to a decrease in symptoms attributed to individual end-organ response to these normal steroids. To the extent that mood symptoms, for example, are due to effects of endogenous steroids on brain neurotransmitter metabolism, use of an oral contraceptive will remove the endogenous steroids as well as the cyclic changes in endogenous steroid levels. However, oral contraceptives have adverse effects on mood for some women, and use of an oral contraceptive preparation may worsen mood rather than improve it.

(3) Cyclic acne will often improve on oral contraceptives, probably due to the estrogen-associated increase in SHBG. Not all women experience an improvement in acne on the older oral contraceptives, the progestins of which are either androgenic or neutral with respect to androgenicity.

(4) Abnormal bleeding or pain associated with endometriosis or adenomyosis may respond well to oral contraceptives. The mechanism of response is not known but may involve progestin-mediated atrophy of the abnormally located endometrial implants.

The one menstrual symptom group that does not respond well to the older oral contraceptives is bloating and breast tenderness. These effects are associated with the oral contraceptive estrogen. Although progesterone, as mentioned above, has anti-aldosterone effects, none of the testosterone-derived progestins, including the nonandrogenic progestins, have anti-aldosterone effects.

The use of drospirenone as an oral contraceptive progestin may offer advantages over the use of other progestins. Drospirenone has anti-aldosterone and anti-androgenic effects, as does spironolactone (Muhn et al, 1995; Fuhrmann et al, 1996). Administration of an oral contraceptive preparation containing ethinyl estradiol and drospirenone to healthy women has been shown to be associated with small but significant decreases in body weight and blood pressure (Oelkers et al, 1995). An increase in serum triglycerides was seen, as has been noted for other oral contraceptive agents. There was no change in glucose tolerance compared to placebo. Another study did not show clinically important changes in weight gain or blood pressure, but found women on a drospirenone-containing oral contraceptive to have an improvement in mood and bloating symptoms over their first year of use of the product (Parsey and Pong, 2000). Whether drospirenone-containing oral contraceptives will be more effective for acne than other oral contraceptives is not known; however, the anti-androgenic effects of drospirenone give reason for optimism.

Serious adverse effects of oral contraceptives include an increase in thromboembolic phenomena and, particularly in smoking women, an increase in myocardial infarction and stroke.There is also an increase in the appearance of hepatic adenomas, which are very uncommon, and an increase in gallbladder disease.

GnRH agonists—GnRH is a hypothalamic peptide that stimulates the pituitary gland to release FSH and LH. In the absence of GnRH activity, minimal FSH and LH are produced, and the ovary is inactive. GnRH is normally produced in a pulsatile fashion, with a pulse every 90 minutes or so. The use of GnRH agonist medications in a manner that results in continual stimulation of the pituitary gland results in eventual down-regulation of GnRH receptor; ie, the pituitary gland becomes refractory to the administered GnRH agonist as well as to native GnRH. The result is a menopause-like state in which there is no cyclic production of ovarian hormones and no menstrual bleeding.

GnRH agonist therapy is very effective for menstrual-associated symptoms. Menopausal symptoms, such as hot flashes, and menopausal effects, such as a loss of bone mineral density, can be controlled by coadministration of add-back hormone replacement therapy. In other words, just as naturally menopausal women can be treated with small doses of estrogen and progestin for symptoms and to prevent bone mineral loss, so too can women on GnRH agonist therapy (Surrey, 1999). Use of GnRH agonist therapy for menstrual-associated symptoms is limited largely by cost. In instances where menstrual symptoms are severe and do not respond to other interventions, GnRH agonist therapy may be very useful. These medications are indicated for the treatment of endometriosis, which can be a cause of dysmenorrhea and abnormal bleeding, but are not indicated for other menstrual-associated symptoms.


The menstrual cycle is a physiologic process controlled by hormones produced by the pituitary gland and ovary. Many women have discomforts associated with the menstrual cycle. In some cases, these discomforts are severe and interfere with normal activities. Breast tenderness and bloating are the most common menstrual symptoms. Mood abnormalities can be the most disrupting menstrual symptoms. Abnormal menstrual bleeding and pain are also important problems in many women. Hormone levels in women with these menstrual problems are almost invariably normal. Although menstrual symptoms can be considered a normal part of life, a number of therapeutic options are available. While no single option works for all women, most will be able find a treatment strategy that works well for them.