Abstract
Perimenopause, as defined by the North American Menopause Society, begins when menstrual cycle length varies by more than seven days and ends 12 months after the final menstrual period. Despite minor differences among definitions, it is consistently understood as the transitional phase from regular ovulatory cycles to anovulation and eventual permanent amenorrhea. This stage typically begins in the early 40s, progresses alongside declining ovarian activity, and culminates in menopause, which occurs between 48 and 52 years of age in Western populations and at a mean age of 48.6 years in Latin America. During this transition, menstrual irregularity becomes common, and symptoms such as vasomotor instability, sleep disturbances, and mood changes frequently emerge as a result of fluctuating estrogen levels. Although overall fertility declines, intermittent ovulation may persist, maintaining the risk of unintended pregnancy. This review summarizes evidence-based contraceptive options appropriate for perimenopausal women, with an emphasis on safety, effectiveness, and clinical applicability during the menopausal transition.
References
Utian WH. Semantics, menopause-related terminology, and the STRAW reproductive aging staging system. Menopause 2001;8(6):398-401.
Reynolds RF, Obermeyer CM. Age at natural menopause in Spain and the United States: results from the DAMES project. Am J Hum Biol. 2005;17(3):331-340.
Castelo-Branco C, Blumel JE, Chedraui P, et.al. Age at menopause in Latin America. Menopause. 2006;13(4):706-712.
Hardman SM, Gebbie AE. Hormonal contraceptive regimens in the perimenopause. Maturitas. 2009;63(3):204-212.
Dunson DB, Columbo B, Baird DD. Changes with age in the level and duration of fertility in the menstrual cycle. Hum Reprod. 2002;17(5):1399-1403.
Weisberg E, Bateson D, Read C, Estoesta J, Lee C. Fertility control: Middle-aged Australian women’s retrospective reports of their pregnancies. Aust N ZJ Public Health. 2008;32(4):390-392.
Jolly M, Sebire N, Haris J, et al. The risks associated with pregnancy in women aged 35 years or older. Hum Reprod. 2000;15:2433-2437.
NCHS, National Survey of Family Growth, 2015–2017. Available from: https://www.cdc.gov/nchs/data/databriefs/db327_tables-508.pdf#3
World Health Organization (WHO). Medical eligibility criteria for contraceptive use, 6th ed. 3 Novemeber. Guideline. Available from: https://www.who.int/publications/i/item/9789240115583
Kailas NA, Sifakis S, Koumantakis E. Contraception during perimenopause. Eur J Contracept Reprod Health Care. 2005;10(1):19-25.
NICE Guideline. Heavy Menstrual Bleeding: CG44. 24 January 2007. Last update 24 August 2016. Available from: nice.org.uk/CG44niceguideline
Blumel JE, Castelo-Branco C, Cancelo MJ, et al. Relationship between psychological complaints and vasomotor symptoms during climacteric. Maturitas. 2004; 49(3):205–210.
Salzer H, Schneider WH, Eppel W. Contraception in preclimacteric women with special regard to oral contraceptives. Wien Med Wochenschr. 1980; 130(6):218–221.
Blumel JE, Castelo-Branco C, Binfa L, et al. A scheme of combined oral contraceptives for women more than 40 years old. Menopause. 2001; 8(4):286–289.
Studd J, Nappi RE. Reproductive depression. Gynecol Endocrinol. 2012; 28(1):42–45.
Bielanski TE. Does adding estrogen to the hormone-free days of an oral contraceptive cycle reduce menopausal symptoms in perimenopausal users? J Fam Pract. 2019; 50(10):838–838.
MacLennan A, Lester S, Moore V. Oral estrogen replacement therapy versus placebo for hot flushes: a systematic review. Climacteric. 2001;4(1):58–74.
Archer DF, Seidman L, Constantine GD, et al. A double-blind placebo-controlled study of desvenlafaxine for vasomotor symptoms. Am J Obstet Gynecol. 2009;200(2):172.e1–172.e10.
Low Dog T. Menopause: a review of botanical dietary supplements. Am J Med. 2005;118(Suppl 12B):98–108.
The North American Menopause Society. The 2023 nonhormone therapy position statement of NAMS. Menopause. 2023;30(6):573–590.
Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295(17):2057–2071.
Freeman EW, Guthrie KA, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267–274.
Chen MN, Lin CC, Liu CF. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric. 2015;18(2):260–269.
Hunter MS. Cognitive behavioral therapy for menopausal symptoms. Climacteric. 2021;24(1):51–56.
Carmody JF, Crawford S, Churchill L. A pilot study of mindfulness-based stress reduction for hot flashes. Menopause. 2006;13(5):760–769.
Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt). 2006;15(1):35–44.
Hannaford PC, Selvaraj S, Elliott AM, et al. Cancer risk among users of oral contraceptives: cohort data from the RCGP oral contraception study. BMJ. 2007;335:651–654.
Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from the RCGP Oral Contraception Study. BMJ. 2010;340:c927.
Gallo MF, Nanda K, Grimes DA, et al. 20 µg versus >20 µg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2013;2013(8):CD003989.
Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11:47–58.
Battipaglia C, Genazzani A, Nappi R, La Marca A. Insights on estetrol, the native estrogen: from contraception to hormone replacement therapy. Minerva Obstet Gynecol. 2024;76(6):590–603.
Gallez A, Blacher S, Maquoi E, et al. Estetrol combined to progestogen for menopause or contraception indication is neutral on breast cancer. Cancers (Basel). 2021;13(10):2486.
Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 studies. Lancet. 2008;371(9609):303–314.
Jahanfar S, Mortazavi J, Lapidow A, et al. Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age: a systematic review. Front Glob Womens Health. 2024;5:1487820.
Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27,276 women. Lancet Oncol. 2015;16(9):1061–1070.
Haraika A, Hercsik T, Amorim das Virgens I, et al. Association of oral contraceptives and risk of endometrial cancer: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2025;104(4):591–603.
Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low-dose OCP on BMD. Maturitas. 2006;54(2):176–180.
Lopez LM, Grimes DA, Schulz KF, Curtis KM. Steroidal contraceptives: effect on bone fractures in women. Cochrane Database Syst Rev. 2009;2009(2):CD006033.
Khalid AB, Krum SA. Estrogen receptors alpha and beta in bone. Bone. 2016;87:130–135.
Ampatzis C, Zervoudis S, Latrakis G, Mastorakos G. Effect of oral contraceptives on bone mineral density. Acta Endocrinol (Buchar). 2022;18(3):355–360.
Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J. Combined oral contraceptives and venous thromboembolism: review and perspective to mitigate the risk. Front Endocrinol (Lausanne). 2021;12:769187.
Jick H, Kaye JA, Vasilakis-Scaramozza C, et al. Risk of venous thromboembolism among users of third-generation oral contraceptives compared with levonorgestrel users before and after 1995. BMJ. 2000;321(7270):1190–1195.
Faculty of Sexual and Reproductive Healthcare. FSRH Guideline. Contraception for Women Aged Over 40 Years. August 2017 (Amended May 2025). Available from: https://www.cosrh.org/Common/Uploaded%20files/documents/fsrh-guideline-contraception-for-women-aged-over-40-years.pdf
Klipping C, Duijkers I, Parke S, Mellinger U, Serrani M, Junge W. Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label randomized crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel. Drugs R D. 2011;11(2):159–170.
Zeun S, Lu M, Uddin A, Zeiler B, Morrison D, Blode H. Pharmacokinetics of an oral contraceptive containing estradiol valerate and dienogest. Eur J Contracept Reprod Health Care. 2009;14(3):221–232.
Bauerfeind A, von Stockum S, Boehnke T, Heinemann K. Venous thromboembolic risk of estradiol valerate–dienogest compared with ethinyl estradiol–levonorgestrel combined oral contraceptives. Obstet Gynecol. 2024;143(3):431–434.
Reed S, Koro C, DiBello J, et al. Safety of nomegestrol acetate/estradiol: PRO-E2 prospective cohort study on venous and arterial thromboembolism. Eur J Contracept Reprod Health Care. 2021;26(6):439–446.
Morimont L, Jost M, Gaspard U, Foidart JM, Dogné JM, Douxfils J. Low thrombin generation in users of a contraceptive containing estetrol and drospirenone. J Clin Endocrinol Metab. 2022;108(1):135–143.
Chen MJ, Jensen JT, Kaunitz AM, et al. Tolerability and safety of the estetrol/drospirenone combined oral contraceptive: pooled analysis of two phase 3 trials. Contraception. 2022;116:44–50.
Douxfils J, Klipping C, Duijkers I, et al. Effect of a contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396–402.
Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res. 2010;126(1):5–11.
Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2006;73(3):223–228.
Khader YS, Rice J, John L, Abueita O. Oral contraceptive use and myocardial infarction risk: meta-analysis. Contraception. 2003;68(1):11–17.
World Health Organization. Cardiovascular disease and steroid hormone contraception. WHO Tech Rep Ser. 1998;877:1–89.
Suwikrom S, Jaisamrarn U. Metabolic effects of oral contraceptive vs nonhormonal methods in women over 40. Contraception. 2005;71(3):183–187.
ESHRE Capri Workshop Group. Hormones and cardiovascular health in women. Hum Reprod Update. 2006;12(5):483–497.
Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: meta-analysis. JAMA. 2000;284(1):72–78.
Baillargeon JP, McClish DK, Essah PA, Nestler JE. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab. 2005;90(7):3863–3870.
Lidegaard O, Kreiner S. Contraceptives and cerebral thrombosis: a five-year national case-control study. Contraception. 2002;65(3):197–205.
Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63.
National Cancer Institute Factsheet: Probability of Breast Cancer in American Women. Available from: http://www.cancernet.gov/cancertopics/factsheet/Detection/probability-breast-cancer
Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377(23):2228–2239.
Fitzpatrick KE, Nichols M, Lyratzopoulos G, et al. Use of progestagen-only contraceptives and breast cancer risk: a UK nested case–control study. PLoS Med. 2023;20(3):e100420.
Beaber EF, Buist DS, Barlow WE, Malone KE. Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age. Cancer Res. 2014;74(15):4078–4089.
Drab A, Wdowiak K, Kanadys W. A global regional comparison of the risk of breast cancer in women using oral contraceptives: systematic review and meta-analysis. Cancers (Basel). 2024;16(23):4044.
Singer CF, Bennink HJ, Natter C, et al. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor–positive early breast cancer. Carcinogenesis. 2014;35(11):2447–2451.
Schmidt M, Lenhard H, Hoenig A, et al. Tumor suppression, dose-limiting toxicity and wellbeing with the fetal estrogen estetrol in patients with advanced breast cancer. J Cancer Res Clin Oncol. 2021;147(6):1833–1842.
Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case–control study. Lancet. 2002;359(9132):1085–1092.
Coffee AL, Sulak PJ, Kuehl TJ. Long-term assessment of symptomatology and satisfaction of an extended oral contraceptive regimen. Contraception. 2007;75(6):444–449.
Jakimiuk AJ, Crosignani PG, Chernev T, et al. High levels of women’s satisfaction and compliance with transdermal contraception: results from a European multinational 6-month study. Gynecol Endocrinol. 2011;27(8):849–856.
Lopez LM, Grimes DA, Gallo MF, Schultz KF. Skin patch and vaginal ring versus combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2008;(1):CD003552.
Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ. Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial. Obstet Gynecol. 2008;112(3):563–571.
Elkind-Hirsch KE, Darensbourg C, Ogden B, Ogden LF, Hindelang P. Contraceptive vaginal ring use has fewer adverse metabolic effects than an oral contraceptive. Contraception. 2007;76(5):348–356.
Murina F, Graziottin A, Di Francesco S, Recalcati D. The impact of the combined contraceptive vaginal ring on the vaginal environment: an observational longitudinal study. Eur J Contracept Reprod Health Care. 2023;28(4):234–237.
Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit. UK Medical Eligibility Criteria for Contraceptive Use. Available from: https://ranzcog.edu.au/wp-content/uploads/FSRH-Medical-Eligibility-Criteria-Contraceptive-Use.pdf
Grimes DA, Lopez LM, O’Brien PA, Raymond EG. Píldoras anticonceptivas de solo progestina. Cochrane Database Syst Rev. 2013;(11):CD007541.
Berenson AB, Radecki CM, Grady JJ, et al. A prospective controlled study of the effects of hormonal contraception on bone mineral density. Obstet Gynecol. 2001;98:576–582.
Hubacher D, Lopez L, Steiner MJ, Dorflinger L. Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons. Contraception. 2009;80(2):113–118.
Arias RD, Jain JK, Brucker C, Ross D, Ray A. Changes in bleeding patterns with depo-medroxyprogesterone acetate subcutaneous injection 104 mg. Contraception. 2006;74(3):234–238.
Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, Secura GM. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;366(21):1998–2007.
Graesslin O, Korver T. The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience. Eur J Contracept Reprod Health Care. 2008;13(Suppl 1):4–12.
Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS. The effects of Implanon on menstrual bleeding patterns. Eur J Contracept Reprod Health Care. 2008;13(Suppl 1):13–28.
Monteiro-Dantas C, Espejo-Arce X, Lui-Filho JF, et al. A three-year longitudinal evaluation of forearm bone density in users of etonogestrel- and levonorgestrel-releasing contraceptive implants. Reprod Health. 2007;4:11.
Lazorwitz A, Seale R, Davis A, Guiahi M. Effect of isotretinoin on serum etonogestrel concentrations in contraceptive implant users. Contraception. 2020;102(1):58–60.
Lazorwitz A, Pena M, Sheeder J, Teal S. Effect of topiramate on serum etonogestrel concentrations among contraceptive implant users. Obstet Gynecol. 2022;139(4):579–587.
Lazorwitz A, Sheeder J, Teal S. The effect of rifampin on serum etonogestrel concentrations and biomarkers of ovulation among contraceptive implant users: a pharmacokinetic and pharmacodynamic study. Contraception. 2023;123:110035.
Depypere HT, Hillard T, Erkkola R, et al. A 60-month non-comparative study on bleeding profiles with the levonorgestrel intrauterine system from the late transition period to estrogen-supplemented menopause. Eur J Obstet Gynecol Reprod Biol. 2010;153(2):176–180.
Boon J, Scholten PC, Oldenhave A, Heintz AP. Continuous intrauterine compared with cyclic oral progestin administration in perimenopausal HRT. Maturitas. 2003;46(1):69–77.
Küçük T, Ertan K. Continuous oral or intramuscular medroxyprogesterone acetate versus the levonorgestrel-releasing intrauterine system in the treatment of perimenopausal menorrhagia: a randomized prospective controlled clinical trial in female smokers. Clin Exp Obstet Gynecol. 2008;35(1):57–60.
Gruber TM, Mechsner S. Pathogenesis of endometriosis: the origin of pain and subfertility. Cells. 2021;10(6):1381.
Hiraoka T, Hirota Y, Fukui Y, et al. Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment. Sci Rep. 2020;10(1):15523.
Letnar G, Andersen K, Olsen T. Risk of stroke in women using levonorgestrel-releasing intrauterine device for contraception. Stroke. 2024;55(7):1830–1837.
Fitzpatrick KE, Nichols M, Lyratzopoulos G, et al. Use of progestagen-only contraceptives and breast cancer risk: a UK nested case–control study. PLoS Med. 2023;20(3):e100420.
Focus 2030. The access to contraception around the world: situational analysis and current challenges. Paris: Focus 2030; 2021. Available from: https://focus2030.org/The-access-to-contraception-around-the-world-situational-analysis-and-current
Haakenstad A, Angelino O, Irvine CMS, et al. Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400(10348):295–327.
World Economic Forum. Cervical cancer: the health gap facing women around the world. Geneva: World Economic Forum; 2024. Available from: https://www.weforum.org/stories/2024/10/cervical-cancer-health-gap/
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