Amenorrhea: A Systematic Approach to Diagnosis and Management

David A. Klein, MD, MPH; Scott L. Paradise, MD; Rachel M. Reeder, MD

Disclosures

Am Fam Physician. 2019;100(1):39-48. 

In This Article

Abstract and Introduction

Abstract

Menstrual patterns can be an indicator of overall health and self-perception of well-being. Primary amenorrhea, defined as the lifelong absence of menses, requires evaluation if menarche has not occurred by 15 years of age or three years post-thelarche. Secondary amenorrhea is characterized by cessation of previously regular menses for three months or previously irregular menses for six months and warrants evaluation. Clinicians may consider etiologies of amenorrhea categorically as outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced. The history should include menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, galactorrhea, and chronic illness. Additional questions may target neurologic, vasomotor, hyperandrogenic, or thyroid-related symptoms. The physical examination should identify anthropometric and pubertal development trends. All patients should be offered a pregnancy test and assessment of serum follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone levels. Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized. Patients with primary ovarian insufficiency can maintain unpredictable ovary function and may require hormone replacement therapy, contraception, or infertility services. Functional hypothalamic amenorrhea may indicate disordered eating and low bone density. Treatment should address the underlying cause. Patients with polycystic ovary syndrome should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk. Amenorrhea can be associated with clinically challenging pathology and may require lifelong treatment. Patients will benefit from ample time with the clinician, sensitivity, and emotional support.

Introduction

Menstrual patterns can be an indicator of overall health status and self-perception of well-being.[1,2]A broad differential is important to avoid missing rare or emergent pathology because many underlying conditions can present as amenorrhea.[3] Primary amenorrhea is the lifelong absence of menses.[3]

Evaluation should be considered if menarche has not occurred by 15 years of age or three years post-thelarche.[1,4] Lack of any pubertal development by 13 years of age should prompt investigation for delayed puberty.[4,5]

Secondary amenorrhea is the cessation of previously regular menses for three months or previously irregular menses for six months and warrants evaluation.[1,3,6] Oligomenorrhea, the lack of menstruation for intervals longer than 35 days in adults or 45 days in adolescents, is approached similarly.[1,3,6–8]

Clinicians should offer a safe and welcoming environment where patients feel comfortable discussing reproductive health concerns by establishing confidentiality, building rapport, and allotting the requisite time needed to talk about possible long-term treatments and sequelae of chronic medical conditions. Preventive health visits should include menstrual cycle education, such as measurement from the first day of menstruation to the first day of the next cycle; intervals are typically 21 to 34 days.[1] Smart phone apps (e.g., Clue) are useful for determining patterns.[9]

Etiologies of amenorrhea can be categorized as: outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced[3,6] (Table 1[1–3,5,6,10–12]). Abnormal pelvic anatomy is important to consider in the evaluation of primary amenorrhea.[3] All causes of secondary amenorrhea may present as primary amenorrhea and the evaluation is similar (Figure 1 and Figure 2).[3]

Figure 1.

Diagnosis of primary amenorrhea.
FSH = follicle-stimulating hormone; LH = luteinizing hormone; TSH = thyroid-stimulating hormone.
*—May be repeated in one month if needed to clarify diagnosis.
Adapted with permission from Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. Am Fam Physician. 2013;87(11):784.

Figure 2.

Diagnosis of secondary amenorrhea.
DHEA-S = dehydroepiandrosterone sulfate; FSH = follicle-stimulating hormone; LH = luteinizing hormone; MRI = magnetic resonance imaging; TSH = thyroid-stimulating hormone.
*—May be repeated in one month if needed to clarify diagnosis.
Adapted with permission from Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. Am Fam Physician. 2013;87(11):785.

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