Chapter 15: Menstrual Disorders and Pelvic Pain

Menstrual dysfunction can signal an underlying abnormality that may have long-term health consequences. Although frequent or prolonged bleeding usually prompts a woman to seek medical attention, infrequent or absent bleeding may seem less troubling and the patient may not bring it to the attention of the physician. Thus, a focused menstrual history is a critical part of every encounter with a female patient. Pelvic pain is a common complaint that may relate to an abnormality of the reproductive organs but also may be of gastrointestinal, urinary tract, or musculoskeletal origin. Depending on its cause, pelvic pain may require urgent surgical attention.

DEFINITION AND PREVALENCE

Amenorrhea refers to the absence of menstrual periods. Amenorrhea is classified as primary if menstrual bleeding has never occurred in the absence of hormonal treatment or secondary if menstrual periods cease for 3–6 months. Primary amenorrhea is a rare disorder that occurs in <1% of the female population. However, between 3 and 5% of women experience at least 3 months of secondary amenorrhea in any specific year. There is no evidence that race or ethnicity influences the prevalence of amenorrhea. However, because of the importance of adequate nutrition for normal reproductive function, both the age at menarche and the prevalence of secondary amenorrhea vary significantly in different parts of the world.

Oligomenorrhea is defined as a cycle length >35 days or <10 menses per year. Both the frequency and the amount of vaginal bleeding are irregular in oligomenorrhea, and moliminal symptoms (premenstrual breast tenderness, food cravings, mood lability), suggestive of ovulation, are variably present. Anovulation can also present with intermenstrual intervals <24 days or vaginal bleeding for >7 days. Frequent or heavy irregular bleeding is termed dysfunctional uterine bleeding if anatomic uterine and outflow tract lesions or a bleeding diathesis has been excluded.

Primary amenorrhea

The absence of menses by age 16 has been used traditionally to define primary amenorrhea. However, other factors, such as growth, secondary sexual characteristics, the presence of cyclic pelvic pain, and the secular trend toward an earlier age of menarche, particularly in African-American girls, also influence the age at which primary amenorrhea should be investigated. Thus, an evaluation for amenorrhea should be initiated by age 15 or 16 in the presence of normal growth and secondary sexual characteristics; age 13 in the absence of secondary sexual characteristics or if height is less than the third percentile; age 12 or 13 in the presence of breast development and cyclic pelvic pain; or within 2 years of breast development if menarche, defined by the first menstrual period, has not occurred.

Secondary amenorrhea or oligomenorrhea

Anovulation and irregular cycles are relatively common for up to 2 years after menarche and for 1–2 years before the final menstrual period. In the intervening years, menstrual cycle length is ~28 days, with an intermenstrual interval normally ranging between 25 and 35 days. Cycle-to-cycle variability in an individual woman who is ovulating consistently is generally +/− 2 days. Pregnancy is the most common cause of amenorrhea and should be excluded early in any evaluation of menstrual irregularity. However, many women occasionally miss a single period. Three or more months of secondary amenorrhea should prompt an evaluation, as should a history of intermenstrual intervals >35 or <21 days or bleeding that persists for >7 days.

DIAGNOSIS

Evaluation of menstrual dysfunction depends on understanding the interrelationships between the four critical components of the reproductive tract: (1) the hypothalamus, (2) the pituitary, (3) the ovaries, and (4) the uterus and outflow tract (Fig. 15-1; Chap. 13). This system is maintained by complex negative and positive feedback loops involving the ovarian steroids (estradiol and progesterone) and peptides (inhibin B and inhibin A) and the hypothalamic (gonadotropin-releasing hormone [GnRH]) and pituitary (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) components of this system (Fig.  15-1).

Disorders of menstrual function can be thought of in two main categories: disorders of the uterus and outflow tract and disorders of ovulation. Many of the conditions that cause primary amenorrhea are congenital but go unrecognized until the time of normal puberty (e.g., genetic, chromosomal, and anatomic abnormalities). All causes of secondary amenorrhea also can cause primary amenorrhea.

Disorders of the uterus or outflow tract

Abnormalities of the uterus and outflow tract typically present as primary amenorrhea. In patients with normal pubertal development and a blind vagina, the differential diagnosis includes obstruction by a transverse vaginal septum or imperforate hymen; müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), which has been associated with mutations in the WNT4 gene; and androgen insensitivity syndrome (AIS), which is an X-linked recessive disorder that accounts for ~10% of all cases of primary amenorrhea (Chap. 11). Patients with AIS have a 46,XY karyotype, but because of the lack of androgen receptor responsiveness, those with complete AIS have severe underandrogenization and female external genitalia. The absence of pubic and axillary hair distinguishes them clinically from patients with müllerian agenesis, as does an elevated testosterone level. Asherman’s syndrome presents as secondary amenorrhea or hypomenorrhea and results from partial or complete obliteration of the uterine cavity by adhesions that prevent normal growth and shedding of the endometrium. Curettage performed for pregnancy complications accounts for >90% of cases; genital tuberculosis is an important cause in regions where it is endemic.

TREATMENT

Disorders of ovulation

Once uterus and outflow tract abnormalities have been excluded, other causes of amenorrhea involve disorders of ovulation. The differential diagnosis is based on the results of initial tests, including a pregnancy test, an FSH level (to determine whether the cause is likely to be ovarian or central), and assessment of hyperandrogenism (Fig. 15-2).

Hypogonadotropic hypogonadism

Low estrogen levels in combination with normal or low levels of LH and FSH are seen with anatomic, genetic, or functional abnormalities that interfere with hypothalamic GnRH secretion or normal pituitary responsiveness to GnRH. Although relatively uncommon, tumors and infiltrative diseases should be considered in the differential diagnosis of hypogonadotropic hypogonadism (Chap. 5). These disorders may present with primary or secondary amenorrhea. They may occur in association with other features suggestive of hypothalamic or pituitary dysfunction, such as short stature, diabetes insipidus, galactorrhea, and headache. Hypogonadotropic hypogonadism also may be seen after cranial irradiation. In the postpartum period, it may be caused by pituitary necrosis (Sheehan’s syndrome) or lymphocytic hypophysitis. Because reproductive dysfunction is commonly associated with hyperprolactinemia from neuroanatomic lesions or medications, prolactin should be measured in all patients with hypogonadotropic hypogonadism (Chap. 5).

Isolated hypogonadotropic hypogonadism (IHH) occurs in women, although it is three times more common in men. IHH generally presents with primary amenorrhea, although 50% have some degree of breast development, and one to two menses have been described in ~10%. IHH is associated with anosmia in about 50% of women (termed Kallmann’s syndrome). Genetic causes of IHH have been identified in ~60% of patients (Chaps. 11 and 13).

Functional hypothalamic amenorrhea (HA) is caused by a mismatch between energy expenditure and energy intake. Recent studies suggest that variants in genes associated with IHH may increase susceptibility to these environmental inputs, accounting in part for the clinical variability in this disorder. Leptin secretion may play a key role in transducing the signals from the periphery to the hypothalamus in HA. The hypothalamic-pituitary-adrenal axis also may play a role. The diagnosis of HA generally can be made on the basis of a careful history, a physical examination, and the demonstration of low levels of gonadotropins and normal prolactin levels. Eating disorders and chronic disease must be specifically excluded. An atypical history, headache, signs of other hypothalamic dysfunction, or hyperprolactinemia, even if mild, necessitates cranial imaging with computed tomography (CT) or magnetic resonance imaging (MRI) to exclude a neuroanatomic cause.

Hypergonadotropic hypogonadism

Ovarian failure is considered premature when it occurs in women <40 years old and accounts for ~10% of secondary amenorrhea. Primary ovarian insufficiency (POI) has generally replaced the terms premature menopause and premature ovarian failure in recognition that this disorder represents a continuum of impaired ovarian function. Ovarian insufficiency is associated with the loss of negative-feedback restraint on the hypothalamus and pituitary, resulting in increased FSH and LH levels. FSH is a better marker of ovarian failure as its levels are less variable than those of LH. Antimüllerian hormone (AMH) levels will also be low in patients with POI, but are more frequently used in management of infertility. As with natural menopause, POI may wax and wane, and serial measurements may be necessary to establish the diagnosis.

Once the diagnosis of POI has been established, further evaluation is indicated because of other health problems that may be associated with POI. For example, POI occurs in association with a variety of chromosomal abnormalities, including Turner’s syndrome, autoimmune polyglandular failure syndromes, radio- and chemotherapy, and galactosemia. The recognition that early ovarian failure occurs in premutation carriers of the fragile X syndrome is important because of the increased risk of severe mental retardation in male children with FMR1 mutations. In the majority of cases, a cause for POI is not determined. Although there are increasing reports of genetic mutations in individuals and families with POI, testing for other than chromosomal abnormalities and FMR1 mutations is not recommended.

Hypergonadotropic hypogonadism occurs rarely in other disorders, such as mutations in the FSH or LH receptors. Aromatase deficiency and 17α-hydroxylase deficiency are associated with decreased estrogen and elevated gonadotropins and with hyperandrogenism and hypertension, respectively. Gonadotropin-secreting tumors in women of reproductive age generally present with high, rather than low, estrogen levels and cause ovarian hyperstimulation or dysfunctional bleeding.

TREATMENT

Polycystic ovarian syndrome (pcos)

PCOS is diagnosed based on a combination of clinical or biochemical evidence of hyperandrogenism, amenorrhea or oligomenorrhea, and the ultrasound appearance of polycystic ovaries. Approximately half of patients with PCOS are obese, and abnormalities in insulin dynamics are common, as is metabolic syndrome. Symptoms generally begin shortly after menarche and are slowly progressive. Lean oligo-ovulatory patients with PCOS generally have high LH levels in the presence of normal to low levels of FSH and estradiol. The LH/FSH ratio is less pronounced in obese patients in whom insulin resistance is a more prominent feature.

TREATMENT

The mechanisms that cause pelvic pain are similar to those that cause abdominal pain and include inflammation of the parietal peritoneum, obstruction of hollow viscera, vascular disturbances, and pain originating in the abdominal wall. Pelvic pain may reflect pelvic disease per se but also may reflect extrapelvic disorders that refer pain to the pelvis. In up to 60% of cases, pelvic pain can be attributed to gastrointestinal problems, including appendicitis, cholecystitis, infections, intestinal obstruction, diverticulitis, and inflammatory bowel disease. Urinary tract and musculoskeletal disorders are also common causes of pelvic pain.

ACUTE PELVIC PAIN

Pelvic inflammatory disease most commonly presents with bilateral lower abdominal pain. It is generally of recent onset and is exacerbated by intercourse or jarring movements. Fever is present in about half of these patients; abnormal uterine bleeding occurs in about one-third. New vaginal discharge, urethritis, and chills may be present but are less specific signs. Adnexal pathology can present acutely and may be due to rupture, bleeding or torsion of cysts, or, much less commonly, neoplasms of the ovary, fallopian tubes, or paraovarian areas. Fever may be present with ovarian torsion. Ectopic pregnancy is associated with right- or left-sided lower abdominal pain, with clinical signs generally appearing 6–8 weeks after the last normal menstrual period. Amenorrhea is present in ~75% of cases and vaginal bleeding in ~50% of cases. Orthostatic signs and fever may be present. Risk factors include the presence of known tubal disease, previous ectopic pregnancies, a history of infertility, diethylstilbestrol (DES) exposure of the mother in utero, or a history of pelvic infections. Threatened abortion may also present with amenorrhea, abdominal pain, and vaginal bleeding. Although more common than ectopic pregnancy, it is rarely associated with systemic signs. Uterine pathology includes endometritis and, less frequently, degenerating leiomyomas (fibroids). Endometritis often is associated with vaginal bleeding and systemic signs of infection. It occurs in the setting of sexually transmitted infections, uterine instrumentation, or postpartum infection.

A sensitive pregnancy test, complete blood count with differential, urinalysis, tests for chlamydial and gonococcal infections, and abdominal ultrasound aid in making the diagnosis and directing further management.

TREATMENT

CHRONIC PELVIC PAIN

Some women experience discomfort at the time of ovulation (mittelschmerz). The pain can be quite intense but is generally of short duration. The mechanism is thought to involve rapid expansion of the dominant follicle, although it also may be caused by peritoneal irritation by follicular fluid released at the time of ovulation. Many women experience premenstrual symptoms such as breast discomfort, food cravings, and abdominal bloating or discomfort. These moliminal symptoms are a good marker of prior ovulation, although their absence is less helpful.

Dysmenorrhea

Dysmenorrhea refers to the crampy lower abdominal midline discomfort that begins with the onset of menstrual bleeding and gradually decreases over the next 12–72 h. It may be associated with nausea, diarrhea, fatigue, and headache and occurs in 60–93% of adolescents, beginning with the establishment of regular ovulatory cycles. Its prevalence decreases after pregnancy and with the use of oral contraceptives.

Primary dysmenorrhea results from increased stores of prostaglandin precursors, which are generated by sequential stimulation of the uterus by estrogen and progesterone. During menstruation, these precursors are converted to prostaglandins, which cause intense uterine contractions, decreased blood flow, and increased peripheral nerve hypersensitivity, resulting in pain.

Secondary dysmenorrhea is caused by underlying pelvic pathology. Endometriosis results from the presence of endometrial glands and stroma outside the uterus. These deposits of ectopic endometrium respond to hormonal stimulation and cause dysmenorrhea, which begins several days before menses. Endometriosis also may be associated with painful intercourse, painful bowel movements, and tender nodules in the uterosacral ligament. Fibrosis and adhesions can produce lateral displacement of the cervix. Transvaginal pelvic ultrasound is part of the initial workup and may detect an endometrioma within the ovary, rectovaginal or bladder nodules, or ureteral involvement. The CA125 level may be increased, but it has low negative predictive value. Definitive diagnosis requires laparoscopy. Symptomatology does not always predict the extent of endometriosis. The prevalence is lower in black and Hispanic women than in Caucasians and Asians. Other secondary causes of dysmenorrhea include adenomyosis, a condition caused by the presence of ectopic endometrial glands and stroma within the myometrium. Cervical stenosis may result from trauma, infection, or surgery.

TREATMENT