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ULY CLINIC

19 Mei 2025, 07:47:14

Amenorrhea

Amenorrhea is defined as the absence of menstrual flow and is classified into two main types: primary and secondary. Primary amenorrhea refers to the failure of menarche to occur by age 16, while secondary amenorrhea denotes the cessation of menstruation for three or more consecutive months in a woman who has previously had normal menstrual cycles, excluding physiological causes such as pregnancy, lactation, or menopause.

Pathophysiology

Pathologic amenorrhea results either from anovulation or from physical obstruction of menstrual outflow. Physical obstructions may include imperforate hymen, cervical stenosis, or intrauterine adhesions (Asherman’s syndrome). Anovulation can be caused by hormonal imbalances, chronic systemic illnesses, psychological stress, excessive physical activity, malnutrition, obesity, or congenital anatomical abnormalities such as absence of ovaries or uterus. Iatrogenic causes include certain medications and hormonal therapies that disrupt the hypothalamic-pituitary-ovarian axis.

Clinical Evaluation

A thorough history and physical examination are paramount in distinguishing between primary and secondary amenorrhea. For primary amenorrhea, inquire about familial menarche patterns, as age at menarche tends to be consistent within families. Evaluate the patient’s overall physical, psychological, and emotional development, since delayed menarche may be influenced by genetic, environmental, or nutritional factors.

In cases of secondary amenorrhea, document menstrual history meticulously, including the age of onset, frequency, and duration of prior menstrual cycles, and any alterations preceding cessation. Assess for associated symptoms such as galactorrhea, weight fluctuations, or signs suggestive of systemic illness.

A detailed review of medical history should emphasize chronic conditions (e.g., anemia), medication use (including hormonal contraceptives), and lifestyle factors such as exercise intensity and psychosocial stressors. Nutritional assessment should explore eating habits and recent weight changes.

Physical examination should include evaluation of secondary sexual characteristics and assessment for signs of virilization or androgen excess. If indicated, a pelvic examination is necessary to identify structural anomalies obstructing menstrual flow.

Medical causes of amenorrhea

Table 1: Medical causes of amenorrhea and associated feature

Cause	Key Features / Associated Signs	Amenorrhea Type
Adrenal tumor	Acne, thinning scalp hair, hirsutism, increased BP, truncal obesity, psychotic changes, asymmetrical ovarian enlargement	Secondary
Adrenocortical hyperplasia	Cushingoid signs: truncal obesity, moon face, buffalo hump, bruises, purple striae, hypertension, renal calculi, hirsutism	Secondary
Adrenocortical hypofunction	Fatigue, irritability, weight loss, pigmentation changes, vitiligo, nausea, vomiting, orthostatic hypotension	Secondary
Amenorrhea-lactation disorders (Forbes-Albright, Chiari-Frommel)	Secondary amenorrhea + lactation without breastfeeding, hot flashes, vaginal atrophy, engorged breasts	Secondary
Anorexia nervosa	Weight loss, thin/emaciated, dry skin, hair loss, lanugo, muscle atrophy, constipation, reduced libido	Primary or Secondary
Congenital absence of ovaries	Absence of secondary sex characteristics	Primary
Congenital absence of uterus	Primary amenorrhea, breast development present	Primary
Corpus luteum cysts	Sudden amenorrhea, acute abdominal pain, breast swelling, tender adnexal mass	Secondary
Hypothalamic tumor	Amenorrhea, endocrine and visual field defects, gonadal underdevelopment, short stature	Secondary
Hypothyroidism	Fatigue, cold intolerance, weight gain, dry skin, bradycardia, hair thinning, constipation, periorbital edema	Primary or Secondary
Mosaicism	Absence of secondary sex characteristics	Primary
Ovarian insensitivity to gonadotropins	Amenorrhea, absence of secondary sex characteristics	Primary
Pituitary tumor	Headache, visual disturbances (bitemporal hemianopsia), acromegaly, Cushingoid signs	Secondary
Polycystic ovary syndrome	Irregular cycles, oligomenorrhea, obesity, hirsutism, deepened voice, enlarged ovaries	Secondary
Pseudoamenorrhea	Anatomical obstruction (e.g., imperforate hymen), cyclic abdominal pain, bulging hymen	Primary
Pseudocyesis	Amenorrhea, lordosis, abdominal distention, nausea, breast enlargement	Secondary
Testicular feminization	Female external genitalia, breast development, scant/absent pubic hair, genetically male	Primary
Thyrotoxicosis	Goiter, nervousness, heat intolerance, tremors, palpitations, tachycardia, weight loss despite appetite	Secondary
Turner’s syndrome	Short stature, webbed neck, broad chest, poor breast/genital development, edema of legs and feet	Primary
Uterine hypoplasia	Underdeveloped uterus detected on exam	Primary
Drugs	Busulfan, chlorambucil, cyclophosphamide, phenothiazines, hormonal contraceptives causing anovulation	Secondary
Radiation therapy	Damage to endometrium or ovaries	Secondary
Surgery	Removal of both ovaries or uterus	Secondary

Special Considerations

In patients with secondary amenorrhea, physical and pelvic examinations must rule out pregnancy before diagnostic testing begins. Typical tests include progestin withdrawal, serum hormone and thyroid function studies, and endometrial biopsy.

Patient Counseling

Explain the treatment and expected outcomes, encourage the patient to discuss her fears, and refer her for psychological counseling if needed.

Pediatric Pointers

Adolescent girls are especially prone to amenorrhea caused by emotional upsets, typically stemming from school, social, or family problems.

Geriatric Pointers

In women older than age 50, amenorrhea usually represents the onset of menopause.

References

Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia: Wolters Kluwer; 2011.
DeCherney AH, Nathan L, Laufer N, Roman AS. Current Diagnosis & Treatment: Obstetrics & Gynecology. 12th ed. New York: McGraw-Hill Education; 2013.
Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders. Endocr Pract. 2001;7(2):120-34.
Nelson HD. Menopause. Lancet. 2008;371(9614):760-70.
De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Hypothalamic-pituitary-adrenal axis disorders. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279035/
Sperling MA. Pediatric Endocrinology. 4th ed. Philadelphia: Saunders Elsevier; 2014.
Berek JS. Berek & Novak’s Gynecology. 16th ed. Philadelphia: Wolters Kluwer; 2019.