Abstract
Clinical guidelines for progestin-only pills (POPs) state that each pill should be
taken at the same time each day, with only a “three-hour window” of tolerance before
back-up contraception should be used. In this commentary, we summarize studies examining
the timing of ingestion and mechanisms of action for various POP formulations and
dosages. We found that different progestins have different properties that determine
the effect of delayed or missed pills on effectiveness at preventing pregnancy. Our
findings highlight that there is more margin for error for some POPs than guidelines
suggest. The three-hour window recommendation should be re-evaluated in light of these
findings. Since clinicians, potential POP users, and regulatory bodies rely on current
guidelines to make decisions about POP use, a critical evaluation and update of these
guidelines are urgently needed.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ContraceptionAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
American College of Obstetricians and Gynecologists. Progestin-only hormonal birth control: pill and injection [Internet]. frequently asked questions: contraception; 2018. 〈https://www.acog.org/Patients/FAQs/Progestin-Only-Hormonal-Birth-Control-Pill-and-Injection?IsMobileSet=false#take〉 (cited September 17, 2019).
Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use [Internet]. 2019. 〈https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/progestin.html〉 (cited September 17, 2019).
- Progestin-only oral contraception: a comprehensive review.Contraception. 1994; 50: S1-195
- Cervical mucus and contraception: what we know and what we don’t.Contraception. 2017; 96: 310-321https://doi.org/10.1016/j.contraception.2017.07.168
- The pre-coital use of mini-dosage progestagens.J Reprod Fertil. 1968; Supplement 5: 167-172
United Nations. Consolidated list of products whose consumption and/or sale have been banned, withdrawn, severely restricted or not approved by governments; 1983.
- The clinical relevance of progestogens in hormonal contraception: present status and future developments.Oncotarget. 2018; 9: 34628-34638https://doi.org/10.18632/oncotarget.26015
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Hormonal contraceptives, progestogens only [Internet]. Hormonal contraception and post-menopausal hormonal therapy. International Agency for Research on Cancer; 1999. 〈https://www.ncbi.nlm.nih.gov/books/NBK396196/〉 (cited September 30, 2022).
- Effects of progestin-only contraceptives on the endometrium.Expert Rev Clin Pharmacol. 2020; 13: 1103-1123https://doi.org/10.1080/17512433.2020.1821649
- Communication between female tract and sperm.Commun Integr Biol. 2009; 2: 82-85https://doi.org/10.4161/cib.7502
- Mechanism of action of a 0.075 mg norgestrel progestogen-only pill 2. Effect on cervical mucus and theoretical risk of conception.Contraception. 2022; 112: 43-47https://doi.org/10.1016/j.contraception.2022.03.016
- Contraceptive failure in the United States.Contraception. 2011; 83: 397-404https://doi.org/10.1016/j.contraception.2011.01.021
- A randomized study evaluating the effect of evidence-based information on clinician attitudes about moving oral contraceptives over the counter.J Women’s Health. 2021; 30: 1626-1636https://doi.org/10.1089/jwh.2020.8706
- Progestin-only pills for contraception.Cochrane Database Syst Rev. 2013; 11CD007541https://doi.org/10.1002/14651858.CD007541.pub3
- Effectiveness and efficacy rates of progestin-only pills: a comprehensive literature review.Contraception. 2022; 119109925https://doi.org/10.1016/j.contraception.2022.109925
- Progestin-only contraceptive pill use among women in the United States.Contraception. 2012; 86: 653-658https://doi.org/10.1016/j.contraception.2012.05.003
- Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake.Contraception. 2016; 93: 303-309https://doi.org/10.1016/j.contraception.2015.12.007
- Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake.Contraception. 2005; 71: 8-13https://doi.org/10.1016/j.contraception.2004.07.016
- Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy.Contraception. 2015; 91: 71-75https://doi.org/10.1016/j.contraception.2014.08.009
- Metabolism of oral contraceptive drugs. The formation and disappearance of metabolites of norethindrone and mestranol after intravenous and oral administration.Am J Obstet Gynecol. 1976; 126: 987-992https://doi.org/10.1016/0002-9378(76)90689-X
- Further study of d-norgestrel for fertility control.Obstet Gynecol. 1975; 46: 308-310
- Effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in HIV-infected women.J Acquir Immune Defic Syndr. 2014; 65: 72-77
- Pharmacokinetic and pharmacodynamic profiles of ethinylestradiol/norgestimate combination or norethindrone upon coadministration with elagolix 150 mg once daily in healthy premenopausal women.Clin Pharmacokinet. 2021; 60: 1003-1013https://doi.org/10.1007/s40262-021-00989-0
- Ovarian function during and after treatment with the new progestagen Org 30659.Fertil Steril. 2001; 76: 108-115https://doi.org/10.1016/S0015-0282(01)01824-6
- A randomised study comparing the effect on ovarian activity of a progestogen-only pill (POP) containing desogestrel and a new POP containing drospirenone in a 24/4 regimen.Eur J Contracept Reprod Health Care. 2015; 20: 419-427https://doi.org/10.3109/13625187.2015.1044082
- Effect of drospirenone on serum potassium and drospirenone pharmacokinetics in women with normal or impaired renal function.J Clin Pharmacol. 2006; 46: 867-875https://doi.org/10.1177/0091270006289973
- Pharmacokinetics of drospirenone and ethinylestradiol in Caucasian and Japanese women.Eur J Contracept Reprod Health Care. 2012; 17: 284-297https://doi.org/10.3109/13625187.2012.677076
- The effect of deliberate non-adherence to a norgestrel progestin-only pill: a randomized, crossover study.Contraception. 2023; 117: 1-6https://doi.org/10.1016/j.contraception.2022.09.002
- Contraceptive mechanism of microdose norethindrone.Obstet Gynecol. 1973; 41: 585-594
- Effect of continuous administration of small doses of chlormadinone acetate on the cervical mucus and postcoital test.Fertil Steril. 1969; 20: 572-580
- Half life.StatPearls. StatPearls Publishing, Treasure Island (FL)2022
- Relevance of half-life in drug design.J Med Chem. 2018; 61: 4273-4282https://doi.org/10.1021/acs.jmedchem.7b00969
- Pharmacokinetics of hormonal contraception in individuals with obesity: a review.Curr Obstet Gynecol Rep. 2020; 9: 72-78https://doi.org/10.1007/s13669-020-00284-y
Medicines and Healthcare products Regulatory Agency. First progestogen-only contraceptive pills to be available to purchase from pharmacies [Internet]. GOV.UK; 2021. 〈https://www.gov.uk/government/news/first-progesterone-only-contraceptive-pills-to-be-available-to-purchase-from-pharmacies〉 (cited March 3, 2022).
Article info
Publication history
Published online: February 16, 2023
Accepted:
February 10,
2023
Received in revised form:
February 7,
2023
Received:
April 2,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
