Amy Hull, Anne Moore, Brooke Faught, Cheryl A. Glass, Erin Shankel, Ginny Moore, Jill C. Cash, Jordan Vaughan, Nancy Pesta Walsh, Rhonda Arthur, and Stefani E. Yudasz
Definition
Amenorrhea is the absence of menstruation when menstrual periods should occur.
A.Primary amenorrhea:
1.No menstrual period by age 14 in the absence of growth or development of secondary sexual characteristics.
2.No menstrual period by age 16 regardless of the presence of normal growth and development with the appearance of secondary sexual characteristics.
B.Secondary amenorrhea: No menstrual period for 6 months in a woman who usually has normal periods, or for a length of time equal to three cycle intervals in a woman with less frequent cycles.
Incidence
A.Amenorrhea in a woman who has had menstrual periods is quite common at some time during her reproductive life. Amenorrhea that is a result of agenesis of part of the reproductive system or a chromosomal anomaly is quite rare. See Pathogenesis
section for the incidence of each cause.
Pathogenesis
A.Physiologic: Pregnancy, breastfeeding, and menopause. Pregnancy is the most common cause of secondary amenorrhea and must be ruled out.
B.Disorders of the central nervous system (CNS; hypothalamic): Hypothalamic amenorrhea is one of the most common types of secondary amenorrhea (28%). There is a deficiency in the pulsatile secretion of gonadotropin-releasing hormone (Gn-RH). Examples include a stressful lifestyle (10%); weight loss, as in anorexia or bulimia (10%); extreme exercise; medications such as hormones, as in postpill amenorrhea; hypothyroidism (10%); and major medical disease such as Crohn’s disease (CD), celiac disease, or systemic lupus erythematosus (SLE).
C.Disorders of the ovary: Examples include abnormal chromosomes such as Turner’s syndrome (0.5%); normal chromosomes (10%) such as in gonadal dysgenesis or agenesis (there may be no or very delayed Tanner stage); premature ovarian failure (POF; premature menopause, before age 40); effect of radiation or chemotherapy; and polycystic ovarian (PCO) disease.
D.Disorders of the outflow tract or uterine target organ: Abnormalities in the systems of this compartment are uncommon. Examples include Asherman’s syndrome from inadvertent endometrial ablation during dilatation and curettage (D&C causes 7% of amenorrhea) and agenesis or structural anomalies of the uterus, tubes, or vagina.
E.Disorders of the anterior pituitary: Examples include prolactin tumors (7.5%).
F.Medications: Examples include certain hormonal contraceptives, chemotherapy drugs, and antipsychotics.
Predisposing Factors
A.The disorder can affect any female between the ages of 14 and 55 years.
Common Complaints
A.I haven’t had a period in months;
I have periods only a few times each year.
B.I have nipple discharge.
C.I am 16 years old and have never had a menstrual period.
Other Signs and Symptoms
A.Irregular, infrequent menstrual periods.
B.Galactorrhea.
C.Pregnancy.
D.Excessive hair growth.
Subjective Data
A.Review complete menstrual history, including age of onset, duration, frequency, regularity, and dysmenorrhea.
B.Review the patient’s pregnancy history.
C.Review the patient’s contraception history.
D.Note other medications the patient is taking, such as hormones or antidepressants.
E.Ask the patient if she has had a major medical disease or treatment, such as chemotherapy for a childhood cancer.
F.Inquire about any breast discharge.
G.Review the patient’s weight pattern.
H.Ask the patient to describe her physical self-image. Does she consider herself obese or fat?
I.Review sources of stress in her life.
J.Discuss exercise pattern and history.
Physical Examination
A.Check height, weight, blood pressure (BP), and pulse.
B.Inspect:
1.Note overall appearance. Look at the neck (thyroid). Inspect the breast/genitalia for sexual maturity. Tanner’s Sexual Maturity Stages descriptions are located at http://childgrowthfoundation.org/wp-content/uploads/2018/05/Puberty-and-the-Tanner-Stages.pdf.
2.Skin assessment: Check for central hair growth, which is androgen responsive. Areas to inspect for coarse hair include the upper lip, chin, sideburns, neck, chest, lower abdomen, and perineum.
C.Palpate:
1.Palpate the neck for thyroid enlargement.
2.Palpate the abdomen for enlarged organs or uterine enlargement compatible with pregnancy.
3.Compress nipples to check for discharge.
D.Auscultate:
1.Auscultate the heart and lungs.
2.If pregnancy is suspected, consider auscultating for fetal heart tones.
E.Pelvic examination:
1.Inspect external genitalia. Note pubic hair pattern for Tanner staging. Note any lesions, masses, or discharge.
2.Speculum examination: Inspect vagina and cervix. Note bluish color, which is Chadwick’s sign with pregnancy.
3.Bimanual examination: Palpate for softening of the cervical isthmus, which is Hegar’s sign for pregnancy. Palpate for size of uterus and for adnexal masses.
Diagnostic Tests
A.Urine: Pregnancy test.
B.Serum:
1.Serum human chorionic gonadotropin (HCG).
2.Thyroid-stimulating hormone (TSH) to rule out thyroid disease.
3.Prolactin: Normal less than 20 ng/mL.
4.Follicle-stimulating hormone (FSH): Greater than 40 IU/mL indicates ovarian failure.
5.Consider luteinizing hormone (LH): FSH ratio to rule out polycystic ovaries.
6.Complete blood count (CBC), complete metabolic profile (CMP) to rule out systemic illness.
7.Serum total testosterone if patient has a hyperandrogenic appearance (hirsutism, cliteromegaly, acne). Normal less than 60 ng/dL.
C.Vaginal and/or pelvic ultrasonography.
D.Consider genetic testing/karyotype analysis in primary amenorrhea.
Differential Diagnoses
A.Amenorrhea.
B.Pregnancy.
C.Constitutional delay.
D.Hypothyroidism.
E.Polycystic ovary syndrome.
F.POF, or early menopause.
G.Perimenopause.
H.Menopause.
I.Pituitary adenoma.
J.Androgen insensitivity syndrome.
K.Anorexia/bulimia.
L.Stressful lifestyle.
M.Medication side effect.
N.Systemic illness.
O.Chromosomal abnormality.
Plan
A.General interventions:
1.If laboratory values are normal, proceed to progesterone challenge test to rule out hypothalamic amenorrhea.
2.If the patient is pregnant, counsel regarding pregnancy and begin antepartum care.
3.If other laboratory information points to an underlying cause for amenorrhea, treat as appropriate.
B. 
See Section III: Patient Teaching Guide Amenorrhea.
C.Pharmaceutical therapy:
1.Progesterone challenge:
a.Medications:
i.Medroxyprogesterone acetate (Provera, Cycrin) 10 mg each day for 5 to 10 days.
ii.Micronized progesterone (Prometrium) 300 mg daily.
iii.One dose of progesterone in oil 200 mg by intramuscular (IM) injection.
b.Positive test is any vaginal bleeding:
i.Bleeding usually occurs within 7 to 10 days after finishing the medicine.
ii.Bleeding confirms an intact hypothalamicpituitary-ovarian (H-P-O) axis and suggests anovulation related to progesterone deficiency. Patient should receive exogenous progesterone to prevent endometrial hyperplasia.
c.In the absence of galactorrhea, with a normal prolactin level, normal TSH, and positive progesterone challenge, further evaluation is unnecessary.
All anovulatory patients require therapeutic management. There is a risk of endometrial cancer with unopposed estrogen. There is a short latent period in progression from a normal endometrium to atypia to cancer, even in a young woman.
2.Progesterone therapy for hypothalamic amenorrhea:
a.Medroxyprogesterone acetate (Provera, Cycrin) 10 mg for 10 days each month.
b.Low-dose oral contraceptive pills.
c.Clomiphene citrate for women desiring pregnancy.
d.Hormone therapy (HT) for perimenopausal women.
Follow-Up
A.Reproductive age: The patient should return after 6 months of treatment with progesterone or oral contraceptive pills. Discontinue the hormones and assess for return of normal periods. If this does not occur, reinstitute progesterone or oral contraceptive therapy.
B.Perimenopausal: Maintain hormonal therapy. The patient should return annually for evaluation.
Consultation/Referral
A.Refer the patient to a physician if there is no withdrawal bleeding from progesterone challenge. The problem is either with the outflow track, which is rare, or with the ovarian production of estrogen or hypothalamic production of gonadotropins. This is usually beyond the scope of the nurse practitioner.
B.Refer the patient to a physician if her prolactin level is elevated (>20 mg/mL) for further workup to rule out pituitary adenoma.
C.If the most likely cause of amenorrhea is an eating disorder or high stress levels, referral for psychological support and cognitive behavioral therapy (CBT) should be considered.
Individual Considerations
A.Older adults: Irregular menses and amenorrhea are common during perimenopause. Provide anticipatory guidance and instructions regarding the need for contraceptive use until menopause is confirmed.