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NR602 Primary Care of the Childbearing and Childrearing Age Week 6 Quiz - 100%
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NR602 Week 6 QuizNR602 Primary Care of the Childbearing and Childrearing Age Week 6 Quiz - 100%
,Anovulation
Anovulation is the failure of the ovary to release ova over a period of time generally exceeding 3 months. The
normal functioning ovary releases one ovum every 25–28 days. This average time between ovulation events is
variable, especially during puberty and the perimenopause period.1 For nonpregnant women aged 16–40
anovulation is considered abnormal and a cause of infertility in 30% of fertility patients.2
One of the cardinal signs of anovulation is irregular or absent menstrual periods. Oligomenorrhea is defined as
more than 36 days between menstrual cycles or fewer than eight cycles per year.3 In the absence of
pregnancy, menstruation follows ovulation by approximately 14 days. Because menstruation is linked to
ovulation, the clinical finding of oligomenorrhea correlates with oligoovulation. This predictable pattern of
ovulation and menstruation is regulated by a cyclic change in hormones. Consequently, the diagnosis of
ovulation dysfunction includes the assessment of the hormones and systems involved in ovulation and not just
the symptom of amenorrhea.
The most important consideration in the workup of anovulation is to determine the patient’s goals. Treatment
of the patient who wants to get pregnant differs from that of the patient who is concerned about the risks of
early menopause. In patients who desire pregnancy, the clinician needs to determine if they are actively trying
for pregnancy, or are planning for pregnancy several years in the future. The approach outlined below begins
with the patient who is actively trying for pregnancy.
History
Many patients with anovulation will present with amenorrhea. Primary amenorrhea is failure to menstruate
and no secondary sexual characteristics by age 14 or no menstruation by age 16 with normal sexual
development.129 Secondary amenorrhea is the cessation of menstruation for more than 3 months. 130 The
etiologies of primary and secondary amenorrhea differ. Primary amenorrhea is often seen in congenital
disorders.131 The most common cause of secondary amenorrhea in women of childbearing age is pregnancy,
consequently the workup for anovulation should begin with a pregnancy test.
Details of a patient’s previous medical history can direct the evaluation of anovulation. Chronic disease can
affect ovulation and may increase risks during pregnancy. 132 Psychiatric problems are also often associated
with ovulation dysfunction. The use of any antipsychotic medications should be noted. 40 Details of previous
pregnancies are likewise important in the evaluation of ovulation and can help distinguish genetic disorders
from later onset anovulation.
Physical
The physical exam should include an evaluation of vital signs, height, weight, BMI, and appearance. Obesity is
commonly associated with anovulation and PCOS.77 Very thin patients may have anorexia or nutritional
deficits. Hirsutism may suggest PCOS, CAH or an androgen secreting tumor. Visual field testing is useful in
patients who report visual changes suggesting a pituitary tumor. Palpation of the thyroid and abdomen should
also be performed to evaluate for masses. Evaluation of the patient with primary amenorrhea should include a
bimanual exam to determine the presence of a patent outflow tract and uterus.
Laboratory tests
, In patients with amenorrhea, pregnancy should be considered and a pregnancy test performed early in the
workup. Evaluation of the HPO axis should be performed in a stepwise fashion. Serum estradiol and
gonadotropins determine ovarian function. FSH measurements have been standardized for day 3 of the
menstrual cycle. However, in patients with amenorrhea a random FSH is appropriate. Measurement of LH has
limited clinical use. The ratio of LH to FSH has been studied for PCOS but is not included in the definition of the
syndrome and is therefore not necessary.77
Elevated FSH indicates an ovarian problem. In patients under 30 years old with an elevated FSH, a karyotype
should be performed. An increased risk of ovarian cancer is seen in XY females with gonadal dysgenesis. 133
Turner syndrome (45,XO) is associated with increased risk for cardiovascular, thyroid, and renal disease. 134 For
these patients, a karyotype is very useful in the workup particularly relating to future pregnancy and health. In
patients with elevated FSH and a normal karyotype, ovarian resistance and POI are considered. A trial of
ovulation induction may be performed using clomiphene citrate as described later. If there is no benefit of
clomiphene, exogenous gonadotropins may be effective.
Normal or decreased FSH values suggest dysfunction of the HPO axis. Subsequent testing includes prolactin,
TSH, and T4. Thyroid abnormalities are very common and may be seen in up to 4% of patients with
infertility.135 Treatment for thyroid disease often restores HPO axis function. Hyperprolactinemia should direct
the clinician to obtain an MRI of the pituitary. Serum prolactin levels greater than 250 μg/L are seen in
prolactin secreting macroadenomas. 136 Macroadenomas may require surgery, while many microadenomas can
be successfully treated with medical therapy.137
In patients with signs of hirsutism, serum androgens including testosterone and dehydroepiandrosterone
(DHEAS) can be evaluated. A testosterone level is a useful androgen test in determining the cause of hirsutism
in women.138 Elevated free testosterone is seen in 70% of women with PCOS. Due to technical limitations in
testing for free testosterone, measurement of total testosterone can be used. DHEAS is produced primarily
from the adrenal gland and elevated levels suggest an adrenal tumor. Many androgen-secreting tumors,
however, cause severe signs of hyperandrogenism including virilization and clitoromegally. 139 A normal DHEAS
level should direct attention to the ovary as the origin of excess androgens. Another useful hormone test in
hirsutism is 17-hydroxyprogesterone. This is produced in the adrenal gland and the ovary, and is elevated in
CAH. Most patients with hirsutism and PCOS will have elevated testosterone levels, while only 25–35% will
have elevated DHEAS.138
An additional laboratory test for patients with PCOS is a 2-hour GTT. 85 This test involves examining insulin and
glucose levels following administration of a 75 g glucose bolus. 140 The glucose tolerance test is useful for
determining insulin resistance. Additionally, obese PCOS patients are at increased risk for dyslipidemia and
metabolic syndrome and a serum lipid profile is appropriate. 141 Elevated lipid levels, particularly in young
patients, may increase the risk of cardiovascular disease later in life. Diet, weight loss, and lifestyle
modifications should be recommended to patients with metabolic syndrome risks.
Imaging tests
Ultrasound is an invaluable tool for the evaluation of gynecologic problems including the assessment of
ovarian architecture, which is a criterion for the diagnosis of PCOS. Transvaginal ultrasound provides a reliable
measurement of the thickness of the endometrial lining. 142 A thickened endometrial lining suggesys the
presence and effect of estrogen. Long term anovulation leads to chronic estrogen stimulation of the uterus
and increases the risk of uterine cancer.143 Since there is not good correlation between thickness and absence
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