Back to Search Results


Post-pill Amenorrhea

Author: Ahn T. Nguyen, MD

Mentor: Gavin F. Jacobson, MD
Editor: Katherine Rivlin, MD

Registered users can also download a PDF or listen to a podcast of this Pearl.
Log in now, or create a free account to access bonus Pearls features.

Combined hormonal contraceptives (CHC), including combined oral contraceptives (COC), inhibit ovulation through hypothalamic-pituitary inhibition of gonadotropin secretion. While no casual relationship has been established between CHC and subsequent amenorrhea, historically, it was believed that this suppression could persist for months after discontinuation of COC, leading to “post-pill amenorrhea.” The name implies pill use, but it could apply after cessation of other combined hormonal methods such as the contraceptive patch or ring. This syndrome has been described as amenorrhea for more than one year after cessation of CHC, with an approximately 1% frequency, (similar to amenorrhea rates in those not using CHCs). When stopping cyclic CHCs, median duration from withdrawal bleeding to first menses is 32 days (range 15-82 days), and 98.9% of uses have clinical evidence of normal hypothalamic-pituitary function within 90 days. Return to fertility after the completion of CHC is generally similar to that observed with other common contraceptive methods (excluding the medroxyprogesterone acetate injectable), including non-hormonal contraceptive methods. Furthermore, the median time to pregnancy is 2.5 to 3 cycles, with a pregnancy rate of nearly 95% after one year.

Patients with post-pill amenorrhea should undergo the same evaluation as any patients with secondary amenorrhea, 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, 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, prolactin, and FSH. An abnormal TSH should prompt further testing for thyroid disease. An elevated prolactin level with normal TSH is generally followed up with an MRI to assess for pituitary tumor. Elevated FSH in patients younger than 40 should prompt an investigation for ovarian insufficiency, including karyotype if younger than 30.  Low or normal FSH levels would suggest further evaluation for 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 that would prompt imaging such as hysterosalpingogram.

The management of secondary amenorrhea can include medical or surgical treatments, depending on the etiology. Thyroid disease requires either medical or surgical treatment, with the needs for thyroxine replacement determined by treatment. Pituitary microadenoma can be managed medically, 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, cyclic hormonal contraception can restore menstrual bleeding  any progestin therapy can reduce the long term risks of unopposed estrogen, and  clomiphene citrate can help with ovulation for patients desiring fertility. Hysteroscopic resection for the treatment of Asherman’s syndrome can restore the menstrual cycle.

Further Reading:

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


********** Notice Regarding Use ************

The Society for Academic Specialists in General Obstetrics and Gynecology, Inc. (“SASGOG”) is committed to accuracy and will review and validate all Pearls on an ongoing basis to reflect current practice.

This document is designed to aid practitioners in providing appropriate obstetric and gynecologic care. Recommendations are derived from major society guidelines and high-quality evidence when available, supplemented by the opinion of the author and editorial board when necessary. It should not be construed as dictating an exclusive course of treatment or procedure to be followed.

Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology. SASGOG reviews the articles regularly; however, its publications may not reflect the most recent evidence. While we make every effort to present accurate and reliable information, this publication is provided “as is” without any warranty of accuracy, reliability, or otherwise, either express or implied. SASGOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or person. Neither SASGOG nor its respective officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.

Copyright 2022 The Society for Academic Specialists in General Obstetrics and Gynecology, Inc. All rights reserved.  No re-print, duplication or posting allowed without prior written consent.

Back to Search Results