Menstrual Problems - Clinical Tree

Normal Menstruation

Data from many countries, including the United States, suggest that the average age of menarche, or first menses, varies according to ethnic origin and socioeconomic status. There is often a close concordance of the age at menarche between mother and daughter, suggesting that genetic factors are determinants in addition to individual factors such as weight, exercise level, and chronic medical conditions. The age of menarche has declined in countries and populations experiencing improved nutritional standards and other living conditions. In U.S. females, the average age of menarche, 12.5 years, has been relatively stable over the last few decades; it is slightly older for non-Hispanic whites, and slightly younger for non-Hispanic blacks and Hispanic Americans.

Menarche typically occurs within 2-3 yr of the onset of breast budding ( thelarche ), which is the 1st sign of puberty in most females. Menarche usually occurs during breast sexual maturity rating ( SMR ; i.e., Tanner stage) 4. Periods gradually become more regular, initially with longer cycle lengths ranging between 21 and 45 days. The older the age at which menarche occurs, the longer it takes for consistently ovulatory cycles to be established. However, for most adolescents, by 3 yr after menarche, menstrual cycles are similar to that of adults: between 21 and 35 days long.

Menstrual Irregularities

In young adolescents, many variations in menstruation are explained by anovulation that results from immaturity of the hypothalamic-pituitary-ovarian axis governing menstrual cyclicity. Significant deviations from normal should prompt a search for organic pathology in a logical and cost-effective manner. An accurate menstrual history is an important, but often lacking, 1st step toward a diagnosis. At menarche, all patients should be encouraged to track their periods, which several free smartphone and tablet applications can facilitate.

Previously, a range of terms has been used to describe abnormal menstrual bleeding. These include “menorrhagia” to indicate regularly occurring bleeding that was excessive in amount or duration, and “metrorrhagia” to indicate irregular bleeding between periods. Such terms are imprecise, confusing, and not linked to any specific underlying pathology. Abnormal uterine bleeding (AUB) is the preferred term for uterine bleeding that is abnormal in regularity, volume, frequency, or duration. AUB is further specified by adding terms that describe the bleeding as heavy menstrual bleeding, or intermenstrual bleeding. A qualifying letter is added to indicate the etiology of the abnormal bleeding. Of the 9 categories of etiologies, the 3 most relevant to adolescents are ovulatory dysfunction (AUB- O ), previously referred to as “dysfunctional uterine bleeding” and discussed in Chapter 142.2 ; coagulopathy (AUB- C ); and not yet classified (AUB- N ).

In addition to a standard medical history noting hospitalizations, chronic illness, and medication use, a complete history for evaluating a patient with menstrual irregularity should include the timing of pubertal milestones, such as onset of pubic and axillary hair and breast development; a detailed patient menstrual history; age of menarche and overall menstrual pattern of mother and sisters; and a family history of gynecologic problems. The complete review of systems should elicit any changes in headache pattern or vision; the presence of galactorrhea; and any changes in skin, hair, or bowel patterns. Changes in diet, level of exercise, and sports participation are also important factors when generating a differential diagnosis. As with all adolescent visits, the patient should be interviewed alone, and the confidential history should assess substance use, consensual sexual activity, forced sexual behavior, abuse, and other psychosocial stressors.

In addition to the basic growth parameters of weight, height, blood pressure, heart rate, and body mass index, a careful review of the patient's growth chart is indicated. Physical examination should document SMR; signs of androgen excess, such as hirsutism or severe acne; and signs suggestive of an eating disorder (see Chapter 41 ), such as lanugo or knuckle calluses. A careful external genital examination should be performed, but in the absence of sexual activity, an internal pelvic examination is rarely necessary. If being considered for the young adolescent, an internal exam should be performed by a physician with expertise in this age-group using proper equipment and technique. Transabdominal pelvic ultrasound can be a useful adjunct for evaluating anatomic abnormalities in the adolescent; when indicated, MRI can provide greater detail of pelvic anatomy.

Amenorrhea

Krishna K. Upadhya
Gina S. Sucato

Keywords

amenorrhea
polycystic ovary syndrome
PCOS
female athlete triad

Amenorrhea, the absence of menstruation, generally requires evaluation at age 15 yr, or if there has been no menstruation within 3 yr of the onset of puberty ( primary amenorrhea ), or if there has been no menstruation for the length of 3 previous cycles in a postmenarchal patient ( secondary amenorrhea ). However, the following caveats exist: lack of any pubertal signs by age 13 yr in a girl should prompt evaluation for pubertal delay; in sexually active patients, or those with other symptoms suggesting pathology, evaluation should be initiated without waiting for 3 missed cycles; in patients whose breast development started between age 8 and 9 yr, observation for >3 yr may be warranted in some cases, given data suggesting that the age of thelarche has decreased but the age of menarche has not. Conversely, expectant management with close follow-up can be considered in a patient whose history, physical examination (showing some signs of pubertal development), and family history suggest constitutional delay of puberty.

The differential diagnosis of amenorrhea is broad ( Table 142.2 ) and requires a careful history and physical exam to guide any necessary diagnostic studies. Key to the evaluation is understanding the timing and tempo of the patient's pubertal milestones. The evaluation of a patient presenting with amenorrhea should begin by ascertaining whether she has ever had any prior menstrual bleeding. Some aspects of the evaluation of both primary and secondary amenorrhea are identical; conditions that can interrupt the menstrual cycle can also prevent menarche. In females with primary amenorrhea, however, genetic and anatomic conditions must also be considered ( Table 142.3 ).

Table 142.2

Causes of Amenorrhea (Primary or Secondary)

Pregnancy (regardless of history can cause primary or secondary amenorrhea)
Functional hypothalamic causes (stress, weight loss, undernutrition, high levels of exercise, energy deficit even at normal weight)
Female athlete triad (inadequate energy intake, amenorrhea, and low bone density)
Eating disorders
Premature ovarian insufficiency (autoimmune, idiopathic, galactosemia, or secondary to radiation or chemotherapy)
Hypothalamic and/or pituitary damage (e.g., irradiation, tumor, traumatic brain injury, surgery, hemochromatosis, midline central nervous system defects such as septooptic dysplasia, autoimmune pituitary hypophysitis)
Thyroid disease (hyper- or hypo-; hypothyroidism more likely to be associated with increased bleeding)
Prolactinoma
Systemic disease (e.g., inflammatory bowel disease, cyanotic congenital heart disease, sickle cell disease, cystic fibrosis, celiac disease)
Hyperandrogenism (polycystic ovary syndrome, nonclassic congenital adrenal hyperplasia, adrenal tumor or dysfunction)
Drugs and medications (e.g., illicit drugs, atypical antipsychotics, hormones)
Turner syndrome (including mosaicism)

Table 142.3

Additional Causes of Primary Amenorrhea

Physiologic/constitutional delay
Anatomic abnormalities
- Müllerian agenesis
- Imperforate hymen
- Transverse vaginal septum
Genetic disorders
- 46,XY disorders of sexual development (e.g., androgen insensitivity syndrome, 5α-reductase deficiency, 17α-hydroxylase deficiency)
- Mixed gonadal dysgenesis (associated with a number of different chromosome patterns)
- Turner syndrome (resulting from 45,X or a variety of mosaic or other abnormal karyotypes)
- Genetic hypogonadotropic hypogonadism (e.g., X-linked Kallmann syndrome)

History and Physical Examination

Important elements of the history include dietary intake, exercise level, and a thorough review of any ongoing symptoms, including fever, headache, vision changes, chronic respiratory or gastrointestinal (GI) complaints, changes in bowel history, galactorrhea, changes in hair or nails, excessive body hair, severe acne, unexplained musculoskeletal complaints, and changes in vaginal discharge (which can disappear in females who are hypoestrogenic for reasons such as poor caloric intake). Any underlying medical conditions and the adequacy of their control should be noted, as well as the presence of any renal or skeletal anomalies, some of which may be associated with reproductive system anomalies. Medications, particularly those for psychiatric conditions, should be documented. Family history of menarcheal age, eating disorders (see Chapter 41 ), and polycystic ovary syndrome (PCOS ; see Chapter 567 ) should be elicited. A thorough social history is necessary, especially concerning the presence or absence of sexual activity or abuse (see Chapter 16.1 ).

Physical examination should begin with careful attention to growth chart trajectories. In addition to a search for undiagnosed systemic disease, clues to an eating disorder, thyroid disease, or hyperandrogenism should be sought. The exam should assess for body mass index, orthostatic pulses, blood pressure, abnormal dentition, anosmia or hyposmia (suggestive of Kallmann syndrome; see Chapter 601.2 ), parotid enlargement, thyroid gland palpation, hepatosplenomegaly or other abdominal mass, lymphadenopathy, presence or absence of breast tissue (by palpation, not inspection), and SMR (see Chapter 132 ). Skin examination should note any lanugo, dry or doughy skin, loss of hair from scalp or eyebrows, striae, acanthosis nigricans, or acne. The genital exam should note SMR and appearance of the vagina, which should be pink and moist; thin, dry, reddened mucosa suggests estrogen deficiency. The clitoral width should be <1 cm. In the patient with primary amenorrhea, vaginal patency can be assessed painlessly using a slender saline-moistened swab and careful avoidance of the hymen. If physical assessment of the cervix and uterus is not tolerated, a pelvic ultrasound is advisable in patients with primary amenorrhea, followed by MRI if more detail is needed.

Laboratory Studies

A urine pregnancy test, serum levels of prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) are reasonable to measure in all patients presenting with amenorrhea ( Fig. 142.1 ). Elevation of FSH (>30 mIU/mL) in an amenorrheic female suggests ovarian insufficiency, and if confirmed with repeat testing, should be followed with a pelvic ultrasound, karyotype, and specialist referral. Diagnostic tests in the patient presenting with amenorrhea should be tailored to her history and physical exam ( Table 142.4 ).

Fig. 142.1, Initial diagnostic testing to evaluate amenorrhea.

Table 142.4

Laboratory Tests to Evaluate Patients With Abnormal Uterine Bleeding

Total and free testosterone *

* In patients with signs or symptoms suggestive of polycystic ovary syndrome, such as acne, hirsutism, obesity, acanthosis nigricans, and a history of infrequent menses.
Liver, kidney, and thyroid function studies
Complete blood count with platelets
Urine pregnancy test (regardless of history)
Nucleic acid amplification test (NAAT) or other equivalent testing for Chlamydia, gonorrhea, and Trichomonas
Prothrombin time and partial thromboplastin time
Ferritin level
Von Willebrand factor antigen, ristocetin cofactor, and factor VIII ^†

† Any abnormalities should be followed with a ristocetin-induced platelet aggregation and von Willebrand factor multimers. Testing in the 1st 3 days of menses and before any estrogen treatment is started minimizes the chances of false-negative tests. Repeat testing can be warranted in patients for whom there is a high pretest suspicion.

activities
Pelvic ultrasound (if bleeding persists despite treatment)

In patients with signs of androgen excess (e.g., severe acne or hirsutism) or other physical stigmata associated with PCOS (rapid pubertal weight gain, acanthosis nigricans) consider measuring levels of 17-hydroxyprogesterone (17-OHP) (collected in the morning, approximately 8 am ), free and total testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione. PCOS affects up to 15% of females; diagnostic criteria for adolescents are controversial but include variations of menstrual irregularity (ranging from amenorrhea to AUB) and physical or biochemical evidence of androgen excess. The interpretation of polycystic ovarian morphology identified on ultrasound in adolescents can be challenging, and an ultrasound is not necessary for diagnosis in adolescents.

With the exceptions of pregnancy, constitutional delay, and imperforate hymen, conditions causing primary amenorrhea are associated with reduced fertility; thus their diagnosis may cause profound emotional responses in patients and families. Therefore, before ordering studies to confirm these diagnoses (e.g., karyotype, MRI of reproductive anatomy), the clinician should carefully consider the implications and be prepared to refer to specialists with experience managing the long-term treatment of such diagnoses.

In patients presumed to have hypothalamic amenorrhea, based on prepubertal luteinizing hormone (LH) and low FSH levels using an ultrasensitive assay and consistent history and physical exam, MRI of the brain is not necessary in all patients. However, MRI should be considered for patients presenting with a headache history that is a change from baseline, persistent emesis, change in thirst, urination, or vision, elevated prolactin or galactorrhea, or other neurologic symptoms.

Treatment

Treatment for amenorrhea varies widely depending on the underlying cause. Many diagnoses require referral to clinicians in specialties such as endocrinology, adolescent medicine, gynecology, and other surgical subspecialists; often, collaboration with other disciplines such as psychology or nutrition is also indicated. For patients with PCOS , the mainstay of treatment is suppression of ovarian androgens (typically with combined hormonal contraception, i.e., estrogen and progestin) and lifestyle modifications to decrease obesity and insulin resistance. Patients with abnormal glucose tolerance may benefit from the addition of metformin. Spironolactone, an androgen receptor blocker, can also be used to reduce androgen effects, including hirsutism. Because of the high prevalence of metabolic syndrome in PCOS, evaluation of comorbid diabetes and hyperlipidemia with periodic lipid screening and oral glucose tolerance testing should be considered, particularly for obese patients, those with familial risk factors, and those with other signs such as acanthosis nigricans and hypertension. For patients with eating disorders or other conditions of energy imbalance that render them hypoestrogenic, normalizing weight and improving nutritional status are the keys to treatment. Initiation of hormonal therapy is not recommended routinely in these patients. However, for those who remain amenorrheic after a trial of nutritional and activity modification, short-term use of transdermal estrogen therapy (E2) may be considered to protect bone health. For females with amenorrhea based on ovarian insufficiency (or absence), exogenous hormones are required for all pubertal development. Experts recommend starting at age 10-12 yr with low-dose transdermal estrogen, progressing to increased doses of estrogen and cyclic progestin. Continued maintenance therapy can be accomplished with higher-dose combination products, as found in typical combined hormonal contraceptive pills, patches, and rings.

For patients with secondary amenorrhea , use of hormones to bring on monthly bleeding (e.g., with combined hormonal contraception) in the absence of a clear indication (e.g., PCOS, contraception) is not recommended, because this will mask the patient's subsequent menstrual pattern. However, in patients with normal postpubertal estrogen levels, progesterone can be useful to periodically (every 4-12 wk) induce shedding of the endometrial lining to avoid buildup and subsequent heavy menses. One commonly used regimen is medroxyprogesterone, 10 mg daily for the 1st 12 days of the month.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Cycle length	21-35 days from the 1st day of one period to the 1st day of the next (during 1st 3 yr after menarche can be 21-45 days)
Duration of menses	7 or fewer days
Blood flow	6 or fewer (soaked) pads or tampons per day