. Menstrual
Disorders During Adolescence
.
Jane I. Tuttle, MS, RN, CPNP, CFNP Concerns about menstrual function are a frequent reason for primary care visits during adolescence. Following a review of normal pubertal development and menstrual function, primary care assessment and management of delayed menarche, amenorrhea, and dysfunctional uterine bleeding during adolescence are presented. J PEDIATR HEALTH CARE. (1991).
5, 197-203.
A
common concern for adolescent females, which frequently results in primary health care visits, is menstrual function. The young woman may come to health care provider because she is bleeding too much, too frequently, irregularly, or with debilitating cramps. Sometimes she seeks care in order to “regulate her periods,” perhaps with the hidden agenda of needing contraception. This article presents the primary care assessment and management of common menstrual function variations and abnormalities. The primary care provider should consider the meaning of menstruation to the individual from a social, Cdhld, and developmental point of view. Family myths about menstruation and the meaning of the “problem” to the individual are important aspects of the history. Much of what brings young women to the primary care provider represents normal developmental phenomena such as anovulation, but the fact that the young client considers it a problem warrants attention. The basic evaluation, techniques of management, and guidelines for referral are presented. Dysfunctional uterine bleeding in the older woman is a separate problem and is beyond the scope of this discussion. Dysmenorrhea has been well covered by Khoiny (1988) and also is omitted here. NORMAL PUBERTY AND MENSTRUAL FUNCTION
n
The onset of puberty and age of menarche (first menstruation) are in large part genetically determined. In the developed world, first menstruation can normally occur as early as 9 years of age or as late as 15 years (Styne & Grumbach, 1986). Once begun, the sequence of the events of puberty occur in a relatively predictable Jane I. Tuttle is an awstant professor Nursing, New Haven, Comecticut.
and nurse practitioner
at Yale School
of
Reprint requests: Jane I. Tuttle, MS, RN, CPNP, CFNP, Yale University School of Nursing, 25 Park St., P 0. Box 9740, New Haven, CT 06536-0740.
25/l/20296
JOURNAL
OF PEDIATRIC
HEALTH
CARE
T
he onset of puberty and age at menarche are in large part genetically determined.
manner (Speroff, Glass, & Kase, 1983). The breast bud (Tanner stage II) should appear by 13 years of age. While on average occurring about 2 years after breast budding, menarche should be attained by 5 years after the breast bud (Styne & Grumbach, 1986). On average, regular ovulation is established about 20 cycles after menarche (Reindollar & McDonough, 1984). Because anovulatory cycles lack the influence of the corpus luteum, which controls cyclic shedding of the endometrium, this normal delay in the establishment of ovulatory cycles explains the majority of irregular menses during adolescence. Menstrual periods may normally last from 2 to 7 days, and may begin at between 2 l- and 45day intervals (Brookman, 1988). Ultimately, an individual’s pattern should become consistent within two or three years of menarche (Coupey & Ahlstrom, 1989). The interrelationship between the physiologic events of the menstrual cycle are shown in Figure 1. n
AMENORRHEA
Lack of menstruation is termed amenorrhea. Traditionally, this condition has been classified as either primary or secondary. Brookman (1989) prefers to refer to primary amenorrhea as delayed menarche because the individual has never menstruated. He refers to other forms of amenorrhea as postmenarchal rather than by the old term “secondary.” By definition, delayed menarche is a condition in which menarche has not occurred by age 15 years or by 5 years after breast budding. Postmenarchal amenorrhea is defined as missing more than three consecutive menstrual periods after at least three flows within a 3- to 6-month period (Brookman, 1989). Having irregular cycles during the first year or two after menarche may be normal, however, a trend toward regularity should be observed. The menstrual cycle is influenced by the entire hypothalamic-pituitary-gonadal
197
198
Volume 5, Number 4 July-August 1991
Tuttle
n FIGURE 1 Schematic representation of the interrelationship of endometrial changes, ovarian func:tion, and patterns of hormone secretion throughout a mature menstrual cycle. (Reprinted with perrnission of Eisevier Science Publishing Co., Inc. From Brookman, R. R. Pediatric and adolescent gynecology case studies, p. 147. Copyright 1981 by Medical Examination Publishing Company, Inc.)
axis, which in turn can be affected by environmental and emotional factors (Malo & Bezdicek, 1986). Evaluation of Delayed Menarche
It is essential to consider delayed menarche in the context of growth and secondary sexual development. Accompanied by overall delay in puberty, failure to attain menarche elicit,s a different set of concerns than would delayed menarche in a girl who has otherwise normal growth and development (Reindollar & McDonough, 1984). Causes of delayed puberty range from chronic systemic illness to chromosomal abnormalities. Amenorrhea accompanied by normal pubertal progression suggests the possibility that an outflow tract abnormality such as imperforate hymen or congenital
absence of part of the reproductive tract is obstructing menstruation. These conditions usually are apparent on pelvic examination and, when suspected, the individual should be referred to a gynecologist. Once chronic illnesses such as Crohn’s disease, general growth delay (for example panhypopituitarism), hypothyroidism, anorexia nervosa, and other systemic diseaseshave been excluded, most casesof delayed puberty are caused either by chromosomally incompetent ovarian failure (CIOF) or chromosomally competent ovarian failure (CCOF) (Rauh, 1983). Some degree of secondary sexual development occurs in many of these conditions, which may make assessment more difficult (Reindollar & McDonough, 1984). History and physical examination are the most im-
Journal of Pediatric Health Care
Menstrual
portant diagnostic t&s in the evaluation of delayed menarche with or without general pubertal delay. Box 1 outlines important elements of the history to obtain for evaluating any menstrual dysfunction. Coupled with, amenorrhea, physical findings such as papilledema, visual field defects, thyromegaly, short stature, abnormal fat distribution, virilization, clitoromegaly, or striae warrant referral to a reproductive endocrinologist. The stigmata of Turner’s syndrome, a chromosome disorder associated with ovarian failure, include short stature, absent or delayed puberty, webbed neck, low hairline, low-set ears, widely spaced nipples, and multiple pigmented nevi (Emans & Goldstein, 1982). If Turner’s syndrome is suspected, consultation with a reproductive endocrinologist is warranted. When specialty referrals are made, the primary care provider continues to have a major role in providing education, emotional support, and coordination of services.
m
m
m
’
Ovarian
Failure
Based on findings from the history and physical examination, various laboratory studies are required (Table 1). High levels of gonadotropic hormones (LH and FSH) in the serum suggest ovarian failure. If the buccal smear reveals an XO,XX/XO mosaicism or a structural abnormality of the second X chromosome, Turner’s syndrome is likely. Various forms of Turner’s syndrome exist, but most forms are associated with gonadal dysgenesis -and failure of estrogenization and incomplete sexual development. If the results of the chromosome analysis are normal, the term chromosomally competent ovarian failure (CCOF) applies. In this case, ovarian failure may be caused by radiation, chemotherapy, Addison’s disease, galactosemia, myotonia dystrophica, sarcoidosis, ataxiatelangiectasia, 17 alpha-hydroxylase deficiency, and the resistant ovary syndrome, in which the ovary presumably lacks adequate receptor sites for gonadotropin function (Rauh, 1983). I f the results of the chromosome normal, the term chromosomally ovarian failure applies.
analysis are competent
Low or normal serum gonadotropins (FSH and LH) suggest that the problem lies further up in the hypothalamic-pituitary-gonadal axis. The presence of normal estrogen levels in the serum provides feedback for the modulation of GnRH (gonadotropin-releasing hormone) in the hypothalamus and hence the regulation of FSH and LH secretion from the pituitary. When gonadal failure exists, the relatively low levels of serum estrogen fail to provide feedback to the hypothalamus,
m
Disorders
199
tye to ~~. may cause viriiization of congenital ‘gevnitwrfinary tract anomdies. Age at puberty and menarche, rate of growth, and sexual development, and grouvth data, which is plotted OR charts so that the prabfem can be viewed in the context of physical development. h&nstrual, sexual, contraceptive, and pregnancy history. Previous menstrual paqf-?rn, and exposure to pregnancy or sexually transmit&d disease, and method of contraception can ali influence menstrual function. Previous surgery, radiation, and chemotherapy. Any of these can cause delayed puberty and/or amenorrhea. Review of systems with special emphasis an a recent history of abdominal pain, diarrhea, headaches, and other symptoms of endocrine or systemic disease, weight changes, galactorrhea, visual field defects, emotional stresses, or competitive athletics. Positive findings in this area suggest that the menstrual disorder may be related to systemic disease or hypothalamic influences. Family history of miscarriages, genetic, endocrine, or bleeding disorders, and age at menarche of first order female relatives because of the strong influence of enetics on menstrual function and to identify familial coagulation disorders.
Data from Emans, S. J. H. & Goldstein, D. P. (1982). Pediatric and Adolescent Cynecobgy (2nd ed.) Boston: Little, Brown, and Company. @beprinted with permission).
and the gonadotropic hormone levels remain high (Reindollar & McDonough, 1984). A technique useful in assessing the ovaries’ production of estrogen in the evaluation of delayed menarche is to determine the estrogenization of the vaginal mucosa. This can be accomplished by asking for an estrin maturation index on the pap smear. The sample should be taken from the vaginal vault because, according to Huflinan (1985), these cells serve as a more reliable indicator of estrogen effect than those located in the distal vagina. The character of the cervical mucus also may provide evidence of estrogenization. Spinnbarkeit, described as clear, stretchy cervical mucus, suggests that vagina mucosa is responding to estrogen. A thin coating of cervical mucus left to dry on a slide, indicates ferning, which looks like complex frost crystals in a fern-like pattern (Fig. 2), and suggests that the
200
Volume 5, Number 4 luiy-August 1991
Tuttle
W TABLE 1 Selected tests used in the evaluation
of menstrual
Buccal smear UUy&ypeI (Normal female of any age = XX) Serwm ptdactin (Mean value for nonpregnant, nonlactating male = 8.5 ng/mf) iandosterone s&ate Dehyd
disorders
Chromosomal analysis of cells from oral
fe-
NJ-fEAs ur OHAS). (~urmal values vary with gender, age and stage of development)
mucosa . Anterior pituitary hormone invokd reproduction and lactation. Androgenk adrenals.
hormone
sec&ed
with
fmm the
Data from Yen & Jaffe, 1986.
mucosa has responded to estrogen. A pink, succulent appearance of the mucosa is also suggestive of estrogen effect and implies normal ovarian production of estrogen. Although typically related to postmenarchal amenorrhea, low weight and strenuous exercise also have been associated with delayed menarche (Bullen et al., 1985; Schwartz et al., 1981; Warren, 1980). If weight loss, stress, chronic disease, or overzealous exercise do not explain the delay in menarche, the possibility of a pituitary lesion should be considered. A relatively common lesion is the pituitary microadenoma or prolactinoma. In this disorder, galactorrhea (a milky discharge from one or both nipples) and visual field defects may be associated with amenorrhea. The serum prolactin level usually is elevated. Another pituitary lesion occurs in patients with Kallman’s syndrome. Symptoms of Kallmann’s syndrome are delayed sexual development and anosmia (lack of a sense of smell). Management
of Delayed Menarche
Primary care providers may be involved in the initial evaluation of patients with delayed menarche. Adolescents who appear to have any of the pathologic conditions discussed previously need specialty evaluation. Outflow tract abnormalities should be referred to a gynecologist. Young women with gonadal failure or general growth delay should be referred to an endocrinologist. Likewise, if a central nervous system lesion is suspected, referral to a neurologist or neurosurgeon may
P
rimary care providers may be involved in the initial evaluation of patients with delayed menarche.
be needed depending on the problem. Pituitary microadenomas are usually managed medically with bromocriptine. Other systemic illnesses should be dealt with appropriately. The primary care provider, however, has a major role in the coordination of services, emotional support, and long-term follow-up of these young women. Evaluation of Postmenarchal
Amenorrhea
Low serum levels of gonadotropic hormones (FSH and LH) with anovulation is the basis for most cases of postmenarchal amenorrhea (Brookman, 1989). Some of the factors that cause delayed menarche, such as stress, thyroid disorders, pituitary lesions, low body weight, and chronic illness also may be associated with postmenarchal amenorrhea. In addition, pregnancy, anorexia nervosa (even before marked weight loss), sudden environmental change, and many other factors can cause a previously menstruating individual to experience amenorrhea (Brookman, 1989; Malo & Bezdicek, 1986).
Even when
an adolescent denies having had sexual intercourse, ruling out pregnancy is essential.
A thorough history and physical examination are again the most important tools in the evaluation of postmenarchal amenorrhea. In addition to those items listed in Table 1, having the client keep a menstrual calendar helps greatly in diagnosing the problem. It is very useful to have all adolescents keep track of their menstrual periods for many reasons. Even when an adolescent denies having had sexual intercourse, ruling out pregnancy is essential.
Journal of Pediatric Health Care
Menstrual
If the lack of menses cannot be explained by any of the factors listed above and in the presence of a normal physical examination and a negative pregnancy test, the progesterone challenge can be used to assesshow well primed the endometrium is by normal ovarian function. Medroxyprogesterone (Provera) 10 mg by mouth once or twice a day for 5 days, or progesterone in oil (DepoProvera) (Upjohn, Kalamazoo, MI) 100 mg intramuscularly once are used to challenge the endometrium. Withdrawal bleeding within 4 to 7 days after discontinuation of the progestin is evidence for an intact hypothalamus-pituitary-gonadal axis and “estrogenprimed” endometrium (Brookman, 1989), and the diagnosis of anovulatory cycles (probably functional) can be made with some confidence. If no bleeding occurs in response to the administration and withdrawal of progestin, or if galactorrhea is present even with a normal prolactin level, the patient should be referred to a reproductive endocrinologist for evaluation and management. The presence of “withdrawal bleeding” does not necessarily rule out polycystic ovary syndrome (commonly known as Stein-Leventhal syndrome). If this diagnosis is suspected on rhe basis of virilizing signs (hirsutism, clitoromegaly, etc.) or obesity, measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid function tests (TFTs), and dehydroepiandrosterone sulfate (DHEA-S) should be considered (McKenna, 1988). A serum LH > 30 mIU/ml with a serum FSH < 10 IU/ml (or a LH : FSH ratio >3 : 1) with or without an elevation in DHEA-S suggests polycystic ovary syndrome (Yen & Jaffe, 1986). Consultation with a reproductive endocrinologist usually is needed when this diagnosis is suspected. Management
of Postmenarchal
Amenorrhea
In the younger adolescent who has good evidence of estrogen effect on the vaginal mucosa and a normal response to the progesterone challenge, menstrual periods probably will return without treatment. However, if amenorrhea/anovulation persists for more than 3 months, there is a risk from unopposed estrogen for endometrial hyperplasia and cancer. Therefore, the client should be “cycled” with medroxyprogesterone (Provera) (Upjohn, Kalamazoo, MI) 10 mg per day by mouth for 5 to 10 days every 3 months. This will induce cyclic shedding. Older adolescents who are amenorrheic and have had menarche at least three years previously also should be treated because they are past the age at which normal cycles should have been established (Speroff, Glass, & Kase, 1983). If contraception is needed, combined oral contraceptives also are a good way to provide cycling. Depot medroxyprogesterone acetate
Disorders
201
FIGURE 2 Ferning. Reprinted with permission from Padilla, S. L., & Craft, K. S. (1985). Anovulation: Etiology, evaluation, and management. The Nurse Practitioner, 10, 28-30, 33-34, 43-44.
n
(Depo-Provera) has not been approved by the Food and Drug Administration as a first-line contraceptive but it is being used in some centers for both contraception and to relieve amenorrhea, using a dose of 100 mg IM every 3 months. Evidence exists for a favorable risk benefit ratio in certain situations, such as those where the client is at high risk for unplanned pregnancy and has difficulty following through with medications (Diczfalusy, 1986; World Health Organization, 1985a, 1985b).
For adolescents
who “fail” the progesterone challenge, further exploration and management of the underlying condition are necessary.
For adolescents who “fail” the progesterone challenge, further exploration and management of the underlying condition are necessary. Consultation with or referral to a gynecologist often is indicated. If virilizing signs and/or elevated DHEA-S suggest androgen excess from either the ovaries (as in polycystic ovary syndrome) or the adrenal glands (resulting from adrenal hyperplasia) an endocrinologist should be consulted because low-dose adrenal corticosteroids may be useful (Speroff, Glass, and Kase, 1983). Galactorrhea suggests a prolactin-secreting lesion in the pituitary gland, and appropriate referral to the endocrinologist or neurologist is indicated. ’ DYSFUNCTIONAL
UTERINE BLEEDING
In contrast to adult women, at least 90% of adolescents who have frequent, excessively heavy, or irregular men-
202
Volume 5, Number 4 July-August 1991
Tuttle
ses do not have a pathologic condition (Brookman, 1989). They therefore generally do not need surgical management or even endometrial biopsy. Anovulatory cycles are extremely common among adolescents and explain so much of the phenomena of dysfunctional uterine bleeding that some experts do not even recommend murh of a laboratory evaluation. In normal menstrual function, the endometrium proliferates during the first half of the cycle. After ovulation, the corpus luteum secretes progesterone, which supports or maintains the endometrium until the fertilized egg is implanted or the corpus luteum disintegrates. It is the withdrawal of progesterone that results in cyclic shedding of the endometrium. Failure to ovulate can result in uncontrolled build-up of the endometrium. As the endometrial height exceeds the ability of the stroma to support it, frequent small bleeds or one large spillover occur. This phenomena results in polymenorrhea, hypermenorrhea, menometrorrhagia, or simply irregular bleeding (Brookman, 1989; Coupey & Ahlstrom, 1989). Presentation of dysfunctional uterine bleeding (DUB) can range from prolonged (> 10 days), frequent (< every 21 days), and/or heavy (> 8 pads or tampons per day) bleeding with anemia (the so-called ‘extravaganza’ bleed) to a vague history of frequent, prolonged, or irregular menstrual periods.
A good
history and menstrual calendar are essential in differentiating normal and dysfunctional uterine bleeding. Evaluation of Dysfunctional
Uterine Bleeding
A good history and menstrual calendar are essential in differentiating normal and dysfunctional uterine bleeding. Age at menarche and duration of the present problem must be d.etermined. If a girl’s first menses results in heavy and uncontrolled bleeding, she should be evaluated for a bleeding disorder (PT, MT). Some cases of coagulation disorders such as von Willebrand’s disease first becolme apparent at the time of menarche (Coupey & Ahlstrom, 1989). Most young women can be reassured that their pattern is normal. Having menstrual periods beginning as frequently as every 21 days is usually normal, but results in a menstrual calendars that looks erratic (for example, menses beginning on April 1, April .22, and May 13). By about three years after menarche, some pattern should have emerged (Yen & Jaffe, 1986). Th e p resence of menstrual cramps suggests ovulatory cycles. Mittelschmerz (pain with ovulation) or midcycle spotting is also suggestive of ovulation. In addition to the history outlined in Table 1, the adolescent who has DUB should be questioned about a personal 0 r f amily history of bleeding disorders or
blood dyscrasias. The review of systems should focus on the thyroid, liver, abdomen, and genitourinary tract. A thorough sexual and contraceptive history should be taken as well, because pregnancy, sexually transmitted diseases (particularly pelvic inflammatory disease), and use of an intrauterine device (IUD) all can be associated with abnormal vaginal bleeding (Coupey & Ahlstrom, 1989). To identify the cause of DUB, physical examination should focus on the reproductive tract, liver, thyroid, body build, and stage of sexual development. Evidence of bleeding such as unexplained bruising and petechiae should be noted. Laboratory evaluation depends on the history and physical examination, but usually a hemoglobin or hematocrit is done along with a pregnancy test. Cervical cultures for chlamydia and gonorrhea should be done in all sexually active clients. Bleeding studies are done selectively as previously noted. Persistam DUB warrants thyroid function tests plus determinations of serum gonadotropic hormones and prola&n levels. Management
of Dysfunctional
Uterine Bleeding
Most authorities agree that once infection, pregnancy, and other systemic diseases have been excluded, management of dysfunctional uterine bleeding should consist of the following (Coupey & Ahlstrom, 1989, Emans & Goldstein, 1982) : . Mild dysfunctional uterine bleeding (DUB), in which the flow is only slightly to moderately increased but with normal hemoglobin levels despite short cycles or relatively long menses, can be managed by observation, reassurance, and iron supplements. n Moderate DUB, defined as persistently short cycles with long and rather heavy flow with mild to moderate anemia, can be managed with medroxyprogesterone (Provera) or norethindrone acetate (Norlutate) (Parke-Davis, Morris Plains, NJ) given orally 10 mg /day for 10 days beginning on the 14th day of the cycle. If it cannot be determined which is day 14, starting on the day of the visit is an alterative. This schedule is repeated beginning 14 days after the onset of withdrawal bleeding for 3 to 6 months. If contraception is an issue or for their convenience, combined oral contraceptives in normal doses can be used instead after the initial withdrawal bleed. If the young woman is in the middle of a heavy flow, she may start taking combined oral contraceptive pills four times per day until the bleeding stops, which takes from between 2 and 5 days (Coupey & Ahlstrom, 1989). Once the bleeding is under control, the adolescent should continue taking one oral contraceptive pill each day until she finishes the pillpack. Continuing com-
Journal of Pediatric Health Care
n
Menstrual
bined oral contraceptive pills in the normal dose for at least three months often is enough to normalize the cycle. Depending on the primary care provider’s experience, education, and comfort level, referral to a gynecologist may be part of the plan of care. Severe DUB, with a hemoglobin level
Disorders During Adolescence
.
Jane I. Tuttle, MS, RN, CPNP, CFNP Concerns about menstrual function are a frequent reason for primary care visits during adolescence. Following a review of normal pubertal development and menstrual function, primary care assessment and management of delayed menarche, amenorrhea, and dysfunctional uterine bleeding during adolescence are presented. J PEDIATR HEALTH CARE. (1991).
5, 197-203.
A
common concern for adolescent females, which frequently results in primary health care visits, is menstrual function. The young woman may come to health care provider because she is bleeding too much, too frequently, irregularly, or with debilitating cramps. Sometimes she seeks care in order to “regulate her periods,” perhaps with the hidden agenda of needing contraception. This article presents the primary care assessment and management of common menstrual function variations and abnormalities. The primary care provider should consider the meaning of menstruation to the individual from a social, Cdhld, and developmental point of view. Family myths about menstruation and the meaning of the “problem” to the individual are important aspects of the history. Much of what brings young women to the primary care provider represents normal developmental phenomena such as anovulation, but the fact that the young client considers it a problem warrants attention. The basic evaluation, techniques of management, and guidelines for referral are presented. Dysfunctional uterine bleeding in the older woman is a separate problem and is beyond the scope of this discussion. Dysmenorrhea has been well covered by Khoiny (1988) and also is omitted here. NORMAL PUBERTY AND MENSTRUAL FUNCTION
n
The onset of puberty and age of menarche (first menstruation) are in large part genetically determined. In the developed world, first menstruation can normally occur as early as 9 years of age or as late as 15 years (Styne & Grumbach, 1986). Once begun, the sequence of the events of puberty occur in a relatively predictable Jane I. Tuttle is an awstant professor Nursing, New Haven, Comecticut.
and nurse practitioner
at Yale School
of
Reprint requests: Jane I. Tuttle, MS, RN, CPNP, CFNP, Yale University School of Nursing, 25 Park St., P 0. Box 9740, New Haven, CT 06536-0740.
25/l/20296
JOURNAL
OF PEDIATRIC
HEALTH
CARE
T
he onset of puberty and age at menarche are in large part genetically determined.
manner (Speroff, Glass, & Kase, 1983). The breast bud (Tanner stage II) should appear by 13 years of age. While on average occurring about 2 years after breast budding, menarche should be attained by 5 years after the breast bud (Styne & Grumbach, 1986). On average, regular ovulation is established about 20 cycles after menarche (Reindollar & McDonough, 1984). Because anovulatory cycles lack the influence of the corpus luteum, which controls cyclic shedding of the endometrium, this normal delay in the establishment of ovulatory cycles explains the majority of irregular menses during adolescence. Menstrual periods may normally last from 2 to 7 days, and may begin at between 2 l- and 45day intervals (Brookman, 1988). Ultimately, an individual’s pattern should become consistent within two or three years of menarche (Coupey & Ahlstrom, 1989). The interrelationship between the physiologic events of the menstrual cycle are shown in Figure 1. n
AMENORRHEA
Lack of menstruation is termed amenorrhea. Traditionally, this condition has been classified as either primary or secondary. Brookman (1989) prefers to refer to primary amenorrhea as delayed menarche because the individual has never menstruated. He refers to other forms of amenorrhea as postmenarchal rather than by the old term “secondary.” By definition, delayed menarche is a condition in which menarche has not occurred by age 15 years or by 5 years after breast budding. Postmenarchal amenorrhea is defined as missing more than three consecutive menstrual periods after at least three flows within a 3- to 6-month period (Brookman, 1989). Having irregular cycles during the first year or two after menarche may be normal, however, a trend toward regularity should be observed. The menstrual cycle is influenced by the entire hypothalamic-pituitary-gonadal
197
198
Volume 5, Number 4 July-August 1991
Tuttle
n FIGURE 1 Schematic representation of the interrelationship of endometrial changes, ovarian func:tion, and patterns of hormone secretion throughout a mature menstrual cycle. (Reprinted with perrnission of Eisevier Science Publishing Co., Inc. From Brookman, R. R. Pediatric and adolescent gynecology case studies, p. 147. Copyright 1981 by Medical Examination Publishing Company, Inc.)
axis, which in turn can be affected by environmental and emotional factors (Malo & Bezdicek, 1986). Evaluation of Delayed Menarche
It is essential to consider delayed menarche in the context of growth and secondary sexual development. Accompanied by overall delay in puberty, failure to attain menarche elicit,s a different set of concerns than would delayed menarche in a girl who has otherwise normal growth and development (Reindollar & McDonough, 1984). Causes of delayed puberty range from chronic systemic illness to chromosomal abnormalities. Amenorrhea accompanied by normal pubertal progression suggests the possibility that an outflow tract abnormality such as imperforate hymen or congenital
absence of part of the reproductive tract is obstructing menstruation. These conditions usually are apparent on pelvic examination and, when suspected, the individual should be referred to a gynecologist. Once chronic illnesses such as Crohn’s disease, general growth delay (for example panhypopituitarism), hypothyroidism, anorexia nervosa, and other systemic diseaseshave been excluded, most casesof delayed puberty are caused either by chromosomally incompetent ovarian failure (CIOF) or chromosomally competent ovarian failure (CCOF) (Rauh, 1983). Some degree of secondary sexual development occurs in many of these conditions, which may make assessment more difficult (Reindollar & McDonough, 1984). History and physical examination are the most im-
Journal of Pediatric Health Care
Menstrual
portant diagnostic t&s in the evaluation of delayed menarche with or without general pubertal delay. Box 1 outlines important elements of the history to obtain for evaluating any menstrual dysfunction. Coupled with, amenorrhea, physical findings such as papilledema, visual field defects, thyromegaly, short stature, abnormal fat distribution, virilization, clitoromegaly, or striae warrant referral to a reproductive endocrinologist. The stigmata of Turner’s syndrome, a chromosome disorder associated with ovarian failure, include short stature, absent or delayed puberty, webbed neck, low hairline, low-set ears, widely spaced nipples, and multiple pigmented nevi (Emans & Goldstein, 1982). If Turner’s syndrome is suspected, consultation with a reproductive endocrinologist is warranted. When specialty referrals are made, the primary care provider continues to have a major role in providing education, emotional support, and coordination of services.
m
m
m
’
Ovarian
Failure
Based on findings from the history and physical examination, various laboratory studies are required (Table 1). High levels of gonadotropic hormones (LH and FSH) in the serum suggest ovarian failure. If the buccal smear reveals an XO,XX/XO mosaicism or a structural abnormality of the second X chromosome, Turner’s syndrome is likely. Various forms of Turner’s syndrome exist, but most forms are associated with gonadal dysgenesis -and failure of estrogenization and incomplete sexual development. If the results of the chromosome analysis are normal, the term chromosomally competent ovarian failure (CCOF) applies. In this case, ovarian failure may be caused by radiation, chemotherapy, Addison’s disease, galactosemia, myotonia dystrophica, sarcoidosis, ataxiatelangiectasia, 17 alpha-hydroxylase deficiency, and the resistant ovary syndrome, in which the ovary presumably lacks adequate receptor sites for gonadotropin function (Rauh, 1983). I f the results of the chromosome normal, the term chromosomally ovarian failure applies.
analysis are competent
Low or normal serum gonadotropins (FSH and LH) suggest that the problem lies further up in the hypothalamic-pituitary-gonadal axis. The presence of normal estrogen levels in the serum provides feedback for the modulation of GnRH (gonadotropin-releasing hormone) in the hypothalamus and hence the regulation of FSH and LH secretion from the pituitary. When gonadal failure exists, the relatively low levels of serum estrogen fail to provide feedback to the hypothalamus,
m
Disorders
199
tye to ~~. may cause viriiization of congenital ‘gevnitwrfinary tract anomdies. Age at puberty and menarche, rate of growth, and sexual development, and grouvth data, which is plotted OR charts so that the prabfem can be viewed in the context of physical development. h&nstrual, sexual, contraceptive, and pregnancy history. Previous menstrual paqf-?rn, and exposure to pregnancy or sexually transmit&d disease, and method of contraception can ali influence menstrual function. Previous surgery, radiation, and chemotherapy. Any of these can cause delayed puberty and/or amenorrhea. Review of systems with special emphasis an a recent history of abdominal pain, diarrhea, headaches, and other symptoms of endocrine or systemic disease, weight changes, galactorrhea, visual field defects, emotional stresses, or competitive athletics. Positive findings in this area suggest that the menstrual disorder may be related to systemic disease or hypothalamic influences. Family history of miscarriages, genetic, endocrine, or bleeding disorders, and age at menarche of first order female relatives because of the strong influence of enetics on menstrual function and to identify familial coagulation disorders.
Data from Emans, S. J. H. & Goldstein, D. P. (1982). Pediatric and Adolescent Cynecobgy (2nd ed.) Boston: Little, Brown, and Company. @beprinted with permission).
and the gonadotropic hormone levels remain high (Reindollar & McDonough, 1984). A technique useful in assessing the ovaries’ production of estrogen in the evaluation of delayed menarche is to determine the estrogenization of the vaginal mucosa. This can be accomplished by asking for an estrin maturation index on the pap smear. The sample should be taken from the vaginal vault because, according to Huflinan (1985), these cells serve as a more reliable indicator of estrogen effect than those located in the distal vagina. The character of the cervical mucus also may provide evidence of estrogenization. Spinnbarkeit, described as clear, stretchy cervical mucus, suggests that vagina mucosa is responding to estrogen. A thin coating of cervical mucus left to dry on a slide, indicates ferning, which looks like complex frost crystals in a fern-like pattern (Fig. 2), and suggests that the
200
Volume 5, Number 4 luiy-August 1991
Tuttle
W TABLE 1 Selected tests used in the evaluation
of menstrual
Buccal smear UUy&ypeI (Normal female of any age = XX) Serwm ptdactin (Mean value for nonpregnant, nonlactating male = 8.5 ng/mf) iandosterone s&ate Dehyd
disorders
Chromosomal analysis of cells from oral
fe-
NJ-fEAs ur OHAS). (~urmal values vary with gender, age and stage of development)
mucosa . Anterior pituitary hormone invokd reproduction and lactation. Androgenk adrenals.
hormone
sec&ed
with
fmm the
Data from Yen & Jaffe, 1986.
mucosa has responded to estrogen. A pink, succulent appearance of the mucosa is also suggestive of estrogen effect and implies normal ovarian production of estrogen. Although typically related to postmenarchal amenorrhea, low weight and strenuous exercise also have been associated with delayed menarche (Bullen et al., 1985; Schwartz et al., 1981; Warren, 1980). If weight loss, stress, chronic disease, or overzealous exercise do not explain the delay in menarche, the possibility of a pituitary lesion should be considered. A relatively common lesion is the pituitary microadenoma or prolactinoma. In this disorder, galactorrhea (a milky discharge from one or both nipples) and visual field defects may be associated with amenorrhea. The serum prolactin level usually is elevated. Another pituitary lesion occurs in patients with Kallman’s syndrome. Symptoms of Kallmann’s syndrome are delayed sexual development and anosmia (lack of a sense of smell). Management
of Delayed Menarche
Primary care providers may be involved in the initial evaluation of patients with delayed menarche. Adolescents who appear to have any of the pathologic conditions discussed previously need specialty evaluation. Outflow tract abnormalities should be referred to a gynecologist. Young women with gonadal failure or general growth delay should be referred to an endocrinologist. Likewise, if a central nervous system lesion is suspected, referral to a neurologist or neurosurgeon may
P
rimary care providers may be involved in the initial evaluation of patients with delayed menarche.
be needed depending on the problem. Pituitary microadenomas are usually managed medically with bromocriptine. Other systemic illnesses should be dealt with appropriately. The primary care provider, however, has a major role in the coordination of services, emotional support, and long-term follow-up of these young women. Evaluation of Postmenarchal
Amenorrhea
Low serum levels of gonadotropic hormones (FSH and LH) with anovulation is the basis for most cases of postmenarchal amenorrhea (Brookman, 1989). Some of the factors that cause delayed menarche, such as stress, thyroid disorders, pituitary lesions, low body weight, and chronic illness also may be associated with postmenarchal amenorrhea. In addition, pregnancy, anorexia nervosa (even before marked weight loss), sudden environmental change, and many other factors can cause a previously menstruating individual to experience amenorrhea (Brookman, 1989; Malo & Bezdicek, 1986).
Even when
an adolescent denies having had sexual intercourse, ruling out pregnancy is essential.
A thorough history and physical examination are again the most important tools in the evaluation of postmenarchal amenorrhea. In addition to those items listed in Table 1, having the client keep a menstrual calendar helps greatly in diagnosing the problem. It is very useful to have all adolescents keep track of their menstrual periods for many reasons. Even when an adolescent denies having had sexual intercourse, ruling out pregnancy is essential.
Journal of Pediatric Health Care
Menstrual
If the lack of menses cannot be explained by any of the factors listed above and in the presence of a normal physical examination and a negative pregnancy test, the progesterone challenge can be used to assesshow well primed the endometrium is by normal ovarian function. Medroxyprogesterone (Provera) 10 mg by mouth once or twice a day for 5 days, or progesterone in oil (DepoProvera) (Upjohn, Kalamazoo, MI) 100 mg intramuscularly once are used to challenge the endometrium. Withdrawal bleeding within 4 to 7 days after discontinuation of the progestin is evidence for an intact hypothalamus-pituitary-gonadal axis and “estrogenprimed” endometrium (Brookman, 1989), and the diagnosis of anovulatory cycles (probably functional) can be made with some confidence. If no bleeding occurs in response to the administration and withdrawal of progestin, or if galactorrhea is present even with a normal prolactin level, the patient should be referred to a reproductive endocrinologist for evaluation and management. The presence of “withdrawal bleeding” does not necessarily rule out polycystic ovary syndrome (commonly known as Stein-Leventhal syndrome). If this diagnosis is suspected on rhe basis of virilizing signs (hirsutism, clitoromegaly, etc.) or obesity, measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid function tests (TFTs), and dehydroepiandrosterone sulfate (DHEA-S) should be considered (McKenna, 1988). A serum LH > 30 mIU/ml with a serum FSH < 10 IU/ml (or a LH : FSH ratio >3 : 1) with or without an elevation in DHEA-S suggests polycystic ovary syndrome (Yen & Jaffe, 1986). Consultation with a reproductive endocrinologist usually is needed when this diagnosis is suspected. Management
of Postmenarchal
Amenorrhea
In the younger adolescent who has good evidence of estrogen effect on the vaginal mucosa and a normal response to the progesterone challenge, menstrual periods probably will return without treatment. However, if amenorrhea/anovulation persists for more than 3 months, there is a risk from unopposed estrogen for endometrial hyperplasia and cancer. Therefore, the client should be “cycled” with medroxyprogesterone (Provera) (Upjohn, Kalamazoo, MI) 10 mg per day by mouth for 5 to 10 days every 3 months. This will induce cyclic shedding. Older adolescents who are amenorrheic and have had menarche at least three years previously also should be treated because they are past the age at which normal cycles should have been established (Speroff, Glass, & Kase, 1983). If contraception is needed, combined oral contraceptives also are a good way to provide cycling. Depot medroxyprogesterone acetate
Disorders
201
FIGURE 2 Ferning. Reprinted with permission from Padilla, S. L., & Craft, K. S. (1985). Anovulation: Etiology, evaluation, and management. The Nurse Practitioner, 10, 28-30, 33-34, 43-44.
n
(Depo-Provera) has not been approved by the Food and Drug Administration as a first-line contraceptive but it is being used in some centers for both contraception and to relieve amenorrhea, using a dose of 100 mg IM every 3 months. Evidence exists for a favorable risk benefit ratio in certain situations, such as those where the client is at high risk for unplanned pregnancy and has difficulty following through with medications (Diczfalusy, 1986; World Health Organization, 1985a, 1985b).
For adolescents
who “fail” the progesterone challenge, further exploration and management of the underlying condition are necessary.
For adolescents who “fail” the progesterone challenge, further exploration and management of the underlying condition are necessary. Consultation with or referral to a gynecologist often is indicated. If virilizing signs and/or elevated DHEA-S suggest androgen excess from either the ovaries (as in polycystic ovary syndrome) or the adrenal glands (resulting from adrenal hyperplasia) an endocrinologist should be consulted because low-dose adrenal corticosteroids may be useful (Speroff, Glass, and Kase, 1983). Galactorrhea suggests a prolactin-secreting lesion in the pituitary gland, and appropriate referral to the endocrinologist or neurologist is indicated. ’ DYSFUNCTIONAL
UTERINE BLEEDING
In contrast to adult women, at least 90% of adolescents who have frequent, excessively heavy, or irregular men-
202
Volume 5, Number 4 July-August 1991
Tuttle
ses do not have a pathologic condition (Brookman, 1989). They therefore generally do not need surgical management or even endometrial biopsy. Anovulatory cycles are extremely common among adolescents and explain so much of the phenomena of dysfunctional uterine bleeding that some experts do not even recommend murh of a laboratory evaluation. In normal menstrual function, the endometrium proliferates during the first half of the cycle. After ovulation, the corpus luteum secretes progesterone, which supports or maintains the endometrium until the fertilized egg is implanted or the corpus luteum disintegrates. It is the withdrawal of progesterone that results in cyclic shedding of the endometrium. Failure to ovulate can result in uncontrolled build-up of the endometrium. As the endometrial height exceeds the ability of the stroma to support it, frequent small bleeds or one large spillover occur. This phenomena results in polymenorrhea, hypermenorrhea, menometrorrhagia, or simply irregular bleeding (Brookman, 1989; Coupey & Ahlstrom, 1989). Presentation of dysfunctional uterine bleeding (DUB) can range from prolonged (> 10 days), frequent (< every 21 days), and/or heavy (> 8 pads or tampons per day) bleeding with anemia (the so-called ‘extravaganza’ bleed) to a vague history of frequent, prolonged, or irregular menstrual periods.
A good
history and menstrual calendar are essential in differentiating normal and dysfunctional uterine bleeding. Evaluation of Dysfunctional
Uterine Bleeding
A good history and menstrual calendar are essential in differentiating normal and dysfunctional uterine bleeding. Age at menarche and duration of the present problem must be d.etermined. If a girl’s first menses results in heavy and uncontrolled bleeding, she should be evaluated for a bleeding disorder (PT, MT). Some cases of coagulation disorders such as von Willebrand’s disease first becolme apparent at the time of menarche (Coupey & Ahlstrom, 1989). Most young women can be reassured that their pattern is normal. Having menstrual periods beginning as frequently as every 21 days is usually normal, but results in a menstrual calendars that looks erratic (for example, menses beginning on April 1, April .22, and May 13). By about three years after menarche, some pattern should have emerged (Yen & Jaffe, 1986). Th e p resence of menstrual cramps suggests ovulatory cycles. Mittelschmerz (pain with ovulation) or midcycle spotting is also suggestive of ovulation. In addition to the history outlined in Table 1, the adolescent who has DUB should be questioned about a personal 0 r f amily history of bleeding disorders or
blood dyscrasias. The review of systems should focus on the thyroid, liver, abdomen, and genitourinary tract. A thorough sexual and contraceptive history should be taken as well, because pregnancy, sexually transmitted diseases (particularly pelvic inflammatory disease), and use of an intrauterine device (IUD) all can be associated with abnormal vaginal bleeding (Coupey & Ahlstrom, 1989). To identify the cause of DUB, physical examination should focus on the reproductive tract, liver, thyroid, body build, and stage of sexual development. Evidence of bleeding such as unexplained bruising and petechiae should be noted. Laboratory evaluation depends on the history and physical examination, but usually a hemoglobin or hematocrit is done along with a pregnancy test. Cervical cultures for chlamydia and gonorrhea should be done in all sexually active clients. Bleeding studies are done selectively as previously noted. Persistam DUB warrants thyroid function tests plus determinations of serum gonadotropic hormones and prola&n levels. Management
of Dysfunctional
Uterine Bleeding
Most authorities agree that once infection, pregnancy, and other systemic diseases have been excluded, management of dysfunctional uterine bleeding should consist of the following (Coupey & Ahlstrom, 1989, Emans & Goldstein, 1982) : . Mild dysfunctional uterine bleeding (DUB), in which the flow is only slightly to moderately increased but with normal hemoglobin levels despite short cycles or relatively long menses, can be managed by observation, reassurance, and iron supplements. n Moderate DUB, defined as persistently short cycles with long and rather heavy flow with mild to moderate anemia, can be managed with medroxyprogesterone (Provera) or norethindrone acetate (Norlutate) (Parke-Davis, Morris Plains, NJ) given orally 10 mg /day for 10 days beginning on the 14th day of the cycle. If it cannot be determined which is day 14, starting on the day of the visit is an alterative. This schedule is repeated beginning 14 days after the onset of withdrawal bleeding for 3 to 6 months. If contraception is an issue or for their convenience, combined oral contraceptives in normal doses can be used instead after the initial withdrawal bleed. If the young woman is in the middle of a heavy flow, she may start taking combined oral contraceptive pills four times per day until the bleeding stops, which takes from between 2 and 5 days (Coupey & Ahlstrom, 1989). Once the bleeding is under control, the adolescent should continue taking one oral contraceptive pill each day until she finishes the pillpack. Continuing com-
Journal of Pediatric Health Care
n
Menstrual
bined oral contraceptive pills in the normal dose for at least three months often is enough to normalize the cycle. Depending on the primary care provider’s experience, education, and comfort level, referral to a gynecologist may be part of the plan of care. Severe DUB, with a hemoglobin level
