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2/1/2016

Secondary Amenorrhea

Author: Ahn T. Nguyen, MD

Mentor: Gavin F. Jacobson, MD
Editor: Christie M. Cooksey, MD MSCR

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Secondary amenorrhea is defined as no menses for 3 months in patients with previously regular menstrual cycles or 6 months in patients with irregular menstrual cycles. The differential diagnosis for secondary amenorrhea is broad, including hypothalamic dysfunction (e.g. weight loss/anorexia), chronic anovulation (e.g. PCOS), hypothyroidism, pituitary abnormalities (e.g. tumor, empty Sella), hyperprolactinemia, and ovarian insufficiency. Less common causes include Asherman’s syndrome, cervical stenosis, ovarian tumors, and non-classical congenital adrenal hyperplasia (CAH).

The evaluation of secondary amenorrhea should begin with a thorough history and physical examination. After excluding pregnancy, the most useful diagnostic tests are TSH and prolactin levels.. An abnormal TSH should prompt further testing for thyroid disease. An elevated prolactin level with normal TSH should be evaluated with an MRI to assess for pituitary tumor. FSH testing is costly and premature menopause is a less common cause of secondary amenorrhea. Elevated FSH in patients younger than 40 should  be followed by an investigation for ovarian insufficiency, including karyotype and testing for Fragile X premutation.  Low or normal FSH levels would suggest further evaluation of conditions causing chronic anovulation. Testing androgens (e.g. testosterone and 17-hydroxyprogesterone) for patients with chronic anovulation and androgenic symptoms can reveal ovarian tumor or non-classical CAH.  History will generally identify potential risk factors for Asherman’s syndrome and cervical stenosis that would prompt imaging such as hysterosalpingogram.

 Delay of return of menses for more than one year after cessation of hormonal contraception occurs in 1% of users, which is similar to amenorrhea rates in those not using hormonal contraception. After cessation, median duration from withdrawal bleeding to first menses is 32 days (range 15-82 days), and 98.9% of users have clinical evidence of normal hypothalamic-pituitary function within 90 days. Return to fertility is generally like that observed with other common contraceptive methods excluding the medroxyprogesterone acetate injectable where return of menses may take up to a year.). Furthermore, the median time to pregnancy is 2.5 to 3 cycles, with a pregnancy rate of nearly 95% after one year.

The management of secondary amenorrhea may be medical or surgical, depending on the etiology. Thyroid disease requires either medical or surgical treatment, and thyroxine replacement may be necessary after obliterative treatment. Pituitary microadenoma can be managed medically with dopamine agonists, but surgery or radiation therapy may be indicated for larger tumors or those refractory to medical management. Ovarian insufficiency can be treated with either CHC or replacement-dose therapy depending on the patient’s need for contraception. In patients with chronic anovulation, CHC’s can restore menstrual bleeding and progestin therapy can reduce the long-term risks of unopposed estrogen. Clomiphene citrate can promote ovulation for patients desiring fertility. Hysteroscopic resection of intrauterine adhesions can restore the menstrual cycle for those patients with Asherman’s syndrome.

Further Reading:

Formerly titled “Post-pill Amenorrhea”, Title revised March 2024.

Initial approval 2/2015; Revised 5/2017; Reaffirmed November 2018; Reaffirmed July 2020; Revised January 2022; Revised March 2024. Revised November 2025.

 

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