From the Guidelines
The management of secondary amenorrhea begins with a thorough diagnostic workup to identify the underlying cause, and treatment depends on the specific etiology, with the goal of addressing the underlying cause, restoring normal hormonal balance, protecting against endometrial hyperplasia, and maintaining bone health. The diagnostic workup should include a pregnancy test to rule out pregnancy, followed by measuring serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid-stimulating hormone (TSH), and estradiol, as suggested by 1. Additional testing may include a progesterone challenge test, pelvic ultrasound, and in some cases, magnetic resonance imaging of the pituitary. For hypothalamic amenorrhea due to excessive exercise or low body weight, lifestyle modifications are recommended, as noted in 1. In polycystic ovary syndrome (PCOS), combined oral contraceptives like ethinyl estradiol 20-35 mcg with progestin are first-line therapy, or alternatively, cyclic progestin therapy such as medroxyprogesterone acetate 10 mg daily for 10-14 days monthly, as discussed in 1. Some key points to consider in the management of secondary amenorrhea include:
- Measuring serum levels of FSH, LH, prolactin, TSH, and estradiol to identify the underlying cause
- Using a progesterone challenge test to evaluate estrogen status and rule out anatomic abnormalities
- Considering pelvic ultrasound and magnetic resonance imaging of the pituitary in some cases
- Lifestyle modifications for hypothalamic amenorrhea due to excessive exercise or low body weight
- Combined oral contraceptives or cyclic progestin therapy for PCOS
- Hormone replacement therapy for primary ovarian insufficiency
- Levothyroxine for hypothyroidism
- Regular follow-up to monitor treatment response and adjust therapy as needed, as emphasized in 1. The most recent and highest quality study, 1, highlights the importance of differentiating between functional hypothalamic amenorrhea (FHA) and polycystic ovary syndrome (PCOS), and considering the presence of polycystic ovarian morphology (PCOM) in the diagnosis and treatment of secondary amenorrhea. Overall, the management of secondary amenorrhea requires a comprehensive approach that takes into account the underlying cause and individual patient needs, with the goal of restoring normal hormonal balance and protecting against long-term health consequences, as noted in 1.
From the FDA Drug Label
Medroxyprogesterone acetate is not recommended in secondary amenorrhea or dysfunctional uterine bleeding. In these conditions oral therapy is recommended. The workup and management of secondary amenorrhea is not directly addressed by the label, except that medroxyprogesterone acetate is not recommended for this condition, and oral therapy is suggested instead 2.
From the Research
Definition and Diagnosis of Secondary Amenorrhea
- Secondary amenorrhea is defined as the cessation of regular menses for three months or the cessation of irregular menses for six months 3, 4, 5.
- The initial workup of secondary amenorrhea includes a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone 3, 6, 5.
- A thorough history and physical examination are essential in narrowing the differential diagnosis of secondary amenorrhea 6, 5.
Causes of Secondary Amenorrhea
- Most cases of secondary amenorrhea can be attributed to polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, or primary ovarian insufficiency 3.
- Other causes of secondary amenorrhea include outflow tract abnormalities, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced causes 5.
Management of Secondary Amenorrhea
- Treatment goals for patients with secondary amenorrhea include prevention of complications such as osteoporosis, endometrial hyperplasia, and heart disease; preservation of fertility; and addressing the underlying cause 3, 6, 5.
- Patients with primary ovarian insufficiency may require hormone replacement therapy, contraception, or infertility services 3, 5.
- Functional hypothalamic amenorrhea may indicate disordered eating and low bone density, and treatment should address these underlying issues 3, 5.
- Patients with polycystic ovary syndrome should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk 3, 5.
Algorithmic Approach to Diagnosis
- An algorithmic approach to laboratory evaluation in the context of secondary amenorrhea can minimize the risk of diagnostic error, decrease test volume, cost, and time to diagnosis 7.
- 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 5.
- Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized 5.