From the Guidelines
Secondary amenorrhea investigations should begin with a pregnancy test, followed by assessment of gonadotropins (FSH, LH), prolactin, TSH, and estradiol levels, as the underlying cause of secondary amenorrhea can significantly impact morbidity, mortality, and quality of life. The initial evaluation is crucial in determining the cause of secondary amenorrhea, which can be due to various factors such as hypothalamic amenorrhea, polycystic ovary syndrome (PCOS), ovarian failure, or hyperprolactinemia 1.
Investigations
Additional tests may include:
- Pelvic ultrasound to assess ovarian morphology and rule out any anatomical abnormalities
- MRI of the pituitary if hyperprolactinemia is present to evaluate for any pituitary tumors
- Progesterone challenge to assess estrogen status and determine if the patient is ovulating These investigations are essential in guiding the management of secondary amenorrhea and preventing long-term complications such as osteoporosis and endometrial hyperplasia.
Management
Management of secondary amenorrhea depends on the underlying cause, and lifestyle modifications are recommended for hypothalamic amenorrhea, while PCOS is treated with combined oral contraceptives or cyclic progestins. For example, patients with PCOS may be treated with medroxyprogesterone acetate 10mg daily for 10-14 days monthly to prevent endometrial hyperplasia 1. Hyperprolactinemia requires dopamine agonists like cabergoline (0.25-1mg twice weekly) or bromocriptine (2.5-7.5mg daily), while thyroid dysfunction needs appropriate thyroid hormone replacement. Premature ovarian insufficiency may require hormone replacement therapy with estradiol (1-2mg daily) and cyclic progesterone (medroxyprogesterone acetate 10mg for 12-14 days monthly or micronized progesterone 200mg daily for 12 days monthly).
Fertility Considerations
For patients desiring fertility, referral to reproductive endocrinology is appropriate, and pulsatile GnRH treatment may be considered as a treatment option for anovulation, as it has been shown to be effective in patients with functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) 1. Regular follow-up is essential to monitor treatment response and adjust therapy as needed, with the goal of restoring normal menstrual cycles, preventing complications, and addressing fertility concerns when relevant.
From the FDA Drug Label
Restoration of menses occurred in 77% of the women treated with cabergoline, compared with 70% of those treated with bromocriptine.
The management option for secondary amenorrhea includes treatment with cabergoline, a dopamine receptor agonist, which has been shown to restore menses in 77% of women treated.
- Investigations for secondary amenorrhea may involve assessing prolactin levels, as hyperprolactinemia is a common cause of secondary amenorrhea.
- Management options, in addition to cabergoline, may include treatment of underlying causes, such as thyroid disorders or polycystic ovary syndrome (PCOS) 2.
From the Research
Investigations for Secondary Amenorrhea
- A systematic evaluation including a detailed history, physical examination, and laboratory assessment of selected serum hormone levels can usually identify the underlying cause of secondary amenorrhea 3, 4
- Initial workup includes a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone 3, 4
- Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized 4
Management Options for Secondary Amenorrhea
- Treatment goals for patients with amenorrhea may vary considerably, and depend on the patient and the specific diagnosis 3
- Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and may require hormone replacement therapy, contraception, or infertility services 3, 4
- Functional hypothalamic amenorrhea may indicate disordered eating and low bone density, and treatment should address the underlying cause 3, 4
- Patients with polycystic ovary syndrome should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk 3, 4
- In cases of Asherman's syndrome, appropriate diagnosis and adequate treatment are mandatory to allow menses and fertility to be restored 5
- Hypothyroidism can be a cause of secondary amenorrhea, and combined therapy for hypothyroidism, menstrual and reproductive dysfunction may be effective 6, 7