Managing menopause in women with diabetes
DOI:
https://doi.org/10.15277/bjd.2024.467Abstract
The impact of the current diabetes pandemic on the menopause experiences and health outcomes of women with diabetes is under-researched and poorly understood.
Type 2 diabetes mellitus (T2DM) often emerges during midlife and, in women, frequently presents synchronously with menopause, which independently increases the cardiometabolic risk.
Recent interest in menopause has highlighted the lack of clinical evidence upon which to base menopause management recommendations for women with diabetes. Most evidence relating to safety and efficacy of menopause hormone therapy (MHT), the first-line treatment for menopause symptoms, is based mainly on Caucasian, socially advantaged women with low rates of co-morbidity. The dearth of data relating to MHT in women with diabetes means that much evidence for women with diabetes relies on extrapolation.
A nuanced and judicious approach to the management of menopause in women with diabetes and associated co-morbidities is, therefore, crucial.
This review focuses on the postmenopausal health risks in women with diabetes and the impact of different types of MHT. It highlights areas of uncertainties and unmet need in menopause care for this cohort of women.
References
Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study Lancet 2023;402(10397):203-34. https://doi.org/10.1016/S0140-6736(23)01301-6
Tomic D, Shaw JE, Magliano The burden and risks of emerging complications of diabetes mellitus. Nat Rev Endocrinol 2022;18(9):525-39. https://doi.org/10.1038/s41574-022-00690-7
Ogurtsova K, Guariguata L, Barengo NC, et al. IDF diabetes atlas: global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract 2022;183: https://doi.org/10.1016/j.diabres.2021.109118
Jeong HG, Park Metabolic disorders in menopause. Metabolites 2022;12(10):954. https://doi.org/10.3390/metabo12100954
Mendoza N, Ramírez I, de la Viuda E, et Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group. Maturitas 2022; 166:65-85. https://doi.org/10.1016/j.maturitas.2022.08.008
Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol 2018;14(4):199-215. https://doi.org/10.1038/nrendo.2017.180
Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100(11):3975- https://doi.org/10.1210/jc.2015-2236
Davis SR, Pinkerton J, Santoro N, Simoncini Menopause--biology, consequences, supportive care, and therapeutic options. Cell 2023;186(19): 4038-58. https://doi.org/10.1016/j.cell.2023.08.016
Hickey M, LaCroix AZ, Doust J, et al. An empowerment model for managing Lancet 2024;403(10430): 947-57. h02799-xttps://doi.org/10.1016/S0140-6736(23)
Pikula A, Gulati M, Bonnet JP, et Promise of lifestyle medicine for heart disease, diabetes mellitus, and cerebrovascular diseases. Mayo Clin Proc Innov Qual Outcomes 2024;8(2):151-65. https://doi.org/10.1016/j.mayocpiqo.2023.11.005
Hemachandra C, Taylor S, Islam RM, Fooladi E, Davis A systematic review and critical appraisal of menopause guidelines. BMJ Sex Reprod Health 2024;50(2):122-38. https://doi.org/10.1136/bmjsrh-202-202099
Crandall CJ, Mehta JM, Manson JE. Management of menopausal symptoms: a JAMA 2023;329(5):405-20. https://doi.org/10.1001/jama.2022.24140
Lederman S, Ottery FD, Cano A, et Fezolinetant for treatment of moderate- to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10382):1091-102. https://doi.org/10.1016/S0140-6736(23)00085-5
Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the treatment of vasomotor symptoms associated with menopause: OASIS 1 and 2 Randomized Clinical JAMA 2024;332(16):1343- https://doi.org/10.1001/jama.2024.14618
Biessels GJ, Despa Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol 2018;14(10):591-604. https://doi.org/10.1038/s41574-018-0048-7
Gong J, Harris K, Lipnicki DM, et al. Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC Alzheimers Dement 2023;19(8):3365-78. https://doi.org/10.1002/alz.12962
Titcomb TJ, Richey P, Casanova R, et Association of type 2 diabetes mellitus with dementia-related and non- dementia-related mortality among postmenopausal women: a secondary competing risks analysis of the women's health initiative. Alzheimers Dement 2024; 20(1):234-42. https://doi.org/10.1002/alz.13416
Grande G, Qiu C, Fratiglioni L. Prevention of dementia in an ageing world: evidence and biological rationale. Ageing Res Rev 2020;64:101045. https://doi.org/10.1016/j.arr.2020.101045
Pertesi S, Coughlan G, Puthusseryppady V, Morris E, Hornberger Menopause, cognition and dementia - a review. Post Reprod Health 2019;25(4):200-6. https://doi.org/10.1177/2053369119883485
Lambrinoudaki I, Paschou SA, Armeni E, Goulis DG. The interplay between diabetes mellitus and menopause: clinical Nat Rev Endocrinol 2022;18(10):608-22. https://doi.org/10.1038/s41574-022-00708-0
Design of the Women's Health Initiative clinical trial and observational The Women's Health Initiative Study Group. Control Clin Trials 1998;19(1):61-109. https://doi.org/10.1016/s0197-2456(97)00078-0
Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol 1996;143(10):971-8. https://doi.org/10.1093/oxfordjournals.aje.a008678
Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) research JAMA 1998; 280(7):605-13. https://doi.org/10.1001/jama.288.1.49
Grady D, Herrington D, Bittner V, et al Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002;288(1): 49-57. https://doi.org/10.1001/jama.288.1.49
García NH, Pérez HA, Spence JD, Armando Risk of vascular disease in premenopausal women with diabetes mellitus. Clin Ther 2014;36(12):1924-34. https://doi.org/10.1016/j.clinthera.2014.06.011
Yihua L, Yun J, Dongshen Coronary artery disease in premenopausal and postmenopausal women. Int Heart J 2017;58(2):174-9. https://doi.org/10.1536/ihj.16-095
Rosendaal FR, Van Hylckama Vlieg A, Tanis BC, Helmerhorst Estrogens, progestogens and thrombosis. J Thromb Haemost 2003;1(7):1371-80. https://doi.org/10.1046/j.1538-7836.2003.00264.x
Scarabin PY. Hormone therapy and venous thromboembolism among postmenopausal Front Horm Res 2014;43:21-32. https://doi.org/10.1159/000360554
Smith NL, Heckbert SR, Lemaitre RN, et al. Esterified estrogens and conjugated equine estrogens and the risk of venous JAMA 2004;292(13):1581-7. https://doi.org/10.1001/jama.292.13.1581
Scarabin PY, Oger E, Plu-Bureau Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet 2003;362(9382):428-32. https://doi.org/10.1016/S0140-6736(03)14066-4
Sweetland S, Beral V, Balkwill A, et Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost 2012;10(11):2277-86. https://doi.org/10.1111/j.1538-7836.2012.04919.x
Kuhl Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8 Suppl 1:3-63. https://doi.org/10.1080/13697130500148875
Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ 2008;336(7655):1227-31. https://doi.org/10.1136/bmj.39555.441944.BE
Bagot CN, Marsh MS, Whitehead M, et al. The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy. J Thromb Haemost 2010;8(8): 1736-44. https://doi.org/10.1111/j.1538-7836.2010.03953.x
Rovinski D, Ramos RB, Fighera TM, Casanova GK, Spritzer PM. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res 2018;168:83-95. https://doi.org/10.1016/j.thromres.2018.06.014
Renoux C, Dell'aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ 2010;340:c2519. https://doi.org/10.1136/bmj.c2519
Hardefeldt PJ, Edirimanne S, Eslick GD. Diabetes increases the risk of breast cancer: a meta-analysis. Endocr Relat Cancer 2012;19(6):793-803. https://doi.org/10.1530/ERC-12-0242
Obeagu EI, Obeagu GU. Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore) 2024;103(3): e36905. https://doi.org/10.1097/MD.000000000036905
Ban KA, Godellas CV. Epidemiology of breast cancer. Surg Oncol Clin N Am 2014;23(3):409-22. https://doi.org/10.1016/j.soc.2014.03.011
Collaborative group on hormonal factors in breast Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019; 394(10204):1159-68. https://doi.org/10.1016/S0140-6736(19)31709-X
Vinogradova Y, Coupland C, Hippisley- Cox Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ 2020;371:m3873. https://doi.org/10.1136/bmj.m3873
Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women's Health Initiative randomized clinical JAMA 2020;324(4):369-80. https://doi.org/10.1001/jama.2020.9482
Støer NC, Vangen S, Singh D, et al. Menopausal hormone therapy breast cancer risk: a population-based cohort study of 1.3 million women in Norway. Br J Cancer 2024;131(1):126-37. https://doi.org/10.1038/s41416-024-02590-1
Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362(9382): 419-27. https://doi.org/10.1016/s0140-6736(03)14065-2
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288(3):321-33. https://doi.org/10.1001/jama.288.3.321
Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008;107(1):103-11. https://doi.org/10.1007/s10549-007-9523-x
Cummings SR, Ettinger B, Delmas, et al. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359(7):697-708. https://doi.org/10.1056/NEJMoa0800743
Skouby SO, Sidelmann JJ, Nilas L, Jespersen J. A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability. Hum Reprod 2007;22(4):1186-91. https://doi.org/10.1093/humrep/del498
Renoux C, Dell'Aniello S, Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J Thromb Haemost 2010;8(5):979-86. https://doi.org/10.1111/j.1538-7836.2010.03839.x
Formoso G, Perrone E, Maltoni S, et al. Short-term and long-term effects of tibolone in postmenopausal women. Cochrane Database Syst Rev 2016; 10(10):Cd008536. https://doi.org/10.1002/14651858.CD008536.pub3
Wang Y, Zeng X, Tan J, Xu Y, Yi C. Diabetes mellitus and endometrial carcinoma: Risk factors and etiological links. Medicine (Baltimore) 2022;101(34): e30299. https://doi.org/10.1097/MD.000000000030299
Luo J, Beresford S, Chen C, et al. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer 2014; 111(7):1432-9. https://doi.org/10.1038/bjc.2014.407
Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet 2022; 399(10333):1412-28. https://doi.org/10.1016/S0140-6736(22)00323-3
Fournier A, Dossus L, Mesrine S, et al. Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008. Am J Epidemiol 2014;180(5):508-17. https://doi.org/10.1093/aje/kwu146
Manley K, Hillard T, Clark J, et al. Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General Practitioners and Getting it Right First Time. Post Reprod Health 2024;30(2):95-116. https://doi.org/10.1177/20533691241254413
Jaacks LM, Vandevijvere S, Pan A, et al. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol 2019;7(3):231-40. https://doi.org/10.1016/S2213-8587(19)30026-9
Lo JC, Chandra M, Yang W, et al. Challenges of fracture risk assessment in Asian and Black women. Am J Manag Care 2024;30(3):140-4. https://doi.org/10.37765/ajmc.2024.89515
Tomasiuk JM, Nowakowska-Płaza A, Wisłowska M, Głuszko P. Osteoporosis and diabetes - possible links and diagnostic difficulties. Reumatologia 2023;61(4):294-304. https://doi.org/10.5114/reum/170048
Zhu L, Jiang X, Sun Y, Shu W. Effect of hormone therapy on the risk of bone fractures: a systematic review and meta-analysis of randomized controlled trials. Menopause 2016;23(4):461-70. https://doi.org/10.1097/GME.000000000519
Mangione CM, Barry MJ, Nicholson WK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement. JAMA 2022;328(17):1740-6. https://doi.org/10.1001/jama.2022.18625
Zhang GQ, Chen JL, Luo Y, et al. Menopausal hormone therapy and women's health: An umbrella review. PLoS Med 2021;18(8):e1003731. https://doi.org/10.1371/journal.pmed.1003731
Flores VA, Pal L, Manson JE. Hormone therapy in menopause: concepts, controversies, and approach to treatment. Endocr Rev 2021;42(6):720-52. https://doi.org/10.1210/endrev/bnab011
Biehl C, Plotsker O, Mirkin S. A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause. Menopause 2019;26(4):431-53. https://doi.org/10.1097/GME.000000001221
Scarabin PY. Progestogens and venous thromboembolism in menopausal women: an updated oral versus transdermal estrogen meta-analysis. Climacteric 2018;21(4):341-5. https://doi.org/10.1080/13697137.2018.1446931
Lopez-Jimenez F, Almahmeed W, Bays H, et al. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation. Eur J Prev Cardiol 2022; 29(17):2218-37. 187 https://doi.org/10.1093/eurjpc/zwac
Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019;364:k4810. https://doi.org/10.1136/bmj.k4810
Morris G, Talaulikar V. Hormone replacement therapy in women with history of thrombosis or a thrombophilia. Post Reprod Health 2023;29(1):33-41. https://doi.org/10.1177/20533691221148036
Davis SR, Baber RJ. Treating menopause - MHT and beyond. Nat Rev Endocrinol 2022;18(8):490-502. https://doi.org/10.1038/s41574-022-00685-4
Weiss R. Menopause and social media: pros and cons for the general public. Maturitas 2023;174:67-8. https://doi.org/10.1016/j.maturitas.2023.02.006
Kauffman RP, MacLaughlin EJ, Courtney LA, Vineyard DD. Fear, misinformation, and pharmaceutical messianism in the promotion of compounded bioidentical hormone therapy. Front Reprod Health 2024;6:1378644. https://doi.org/10.3389/frph.2024.1378644
The Lancet (Editorial). Time for a balanced conversation about menopause. Lancet 2024;403(10430): 877. https://doi.org/10.1016/S0140-6736(24)00462-8
Hamoda H, Mukherjee A, Morris E, et al. Optimising the menopause transition: Joint position statement by the British Menopause Society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology on best practice recommendations for the care of women experiencing the menopause. Post Reprod Health 2022;28(3):121-2. https://doi.org/10.1177/20533691221104882
Panay N, Ang SB, Cheshire R, Goldstein SR, Maki P, Nappi RE. Menopause and MHT in 2024: addressing the key controversies - an International Menopause Society White Paper. Climacteric 2024;27(5):441-57. https://doi.org/10.1080/1697137.2024.2394950
Published
Issue
Section
License
Manuscripts published in the June 2024 edition and after in the BJD have been published in open access under a Creative Commons Attribution 4.0 International License and available at https://www.bjd-abcd.com. Prior year articles are available free of charge via our website.