Are progestins really necessary as part of a combined HRT regimen?

References

• Smith DC, Prentice R, Thompson D, Herman W. Association of exogenous estrogens and endometrial carcinoma. N Engl J Med 1975;293:1164–7
   PubMed Web of Science ®Google Scholar
• Ziel H, Finkle W. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 1975;293:1167–70
   PubMed Web of Science ®Google Scholar
• Antunes CMF, Stolley PD, Rosenstein MB. Endometrial cancer and estrogen use. Report of a large case control study. N Engl J Med 1979;300:9–13
   PubMed Web of Science ®Google Scholar
• Roussow 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;288:321–33
   PubMed Web of Science ®Google Scholar
• Cheblowski RT, Hendrix SL, Lander RD, et al., for the Women's Health Initiative randomized trial. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. JAMA 2003;289:3243–53
   PubMed Web of Science ®Google Scholar
• Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammographic screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647–57
   PubMed Web of Science ®Google Scholar
• Beral V; Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 2003;362:419–27
   PubMed Web of Science ®Google Scholar
• Lethaby A, Suckling J, Barlow D, et al. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004; 3:CD000402
   Google Scholar
• Green PK, Weiss NS, McKnight B, et al. Risk of endometrial cancer following cessation of menopausal hormone use. Cancer Causes Control 1996;7:575–80
   PubMed Web of Science ®Google Scholar
• Casper RF. Regulation of estrogen/progestogen receptors in the endometrium. Int J Fertil & Menopause Studies 1996;41: 16–21
   PubMed Web of Science ®Google Scholar
• Paterson MEL, Wade-Evans T, Sturdee DW, et al. Endometrial disease after treatment with oestrogens and progestogens in the climacteric. BMJ 1980;280:822–4
   PubMed Web of Science ®Google Scholar
• Sturdee DW, Ulrich LG, Barlow DH, et al. The endometrial response to sequential and continuous combined oestrogen- progestogen replacement therapy. BJOG 2000;107:1392–400
   PubMed Web of Science ®Google Scholar
• Archer DF, McIntyre-Seltman K, Wilborn WW Jr, et al.Endometrial morphology in asymptomatic postmenopausal women. Am J Obstet Gynecol 1991;165:317–22
   PubMed Web of Science ®Google Scholar
• Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1996;275:370–5
   PubMed Web of Science ®Google Scholar
• Wiederpass E. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 1999;91:1131–7
   PubMed Web of Science ®Google Scholar
• David A, Czernobilsky B, Weisglass L. Long cyclic hormonal cycle therapy in postmenopausal women. In Berg G, Hammar M, eds. The Modern Management of the Menopause. Proceedings of the VII International Congress on the Menopause. London: Parthenon Publishing, 1994:463–70
   Google Scholar
• Bjarnason K, Cerin A, Lindgren R, Weber T. The Scandinavian Long Cycle Study Group. Adverse endometrial effects during long cycle hormone replacement therapy. Maturitas 1999;32:161–70
   Google Scholar
• Erkkola R, Kumento U, Lehmuskoski S, et al. No increased risk of endometrial hyperplasia with fixed long-cycle oestrogen- progestogen therapy after five years. J Brit Menop Soc 2004;10: 9–13
   PubMedGoogle Scholar
• Whitehead ML, Townsend PT, Pryse-Davies J, et al. Effects of estrogens and progestins on the biochemistry and morphology of the postmenopausal endometrium. N Engl J Med 1981;305: 1599–605
   PubMed Web of Science ®Google Scholar
• Staland B. Continuous treatment with a combination of estrogen and gestagen – a way of avoiding endometrial stimulation. Acta Obstet Gynecol Scand 1982;130(Suppl):29–35
   Google Scholar
• Mattsson L-Å, Cullberg G, Samsioe G. Evaluation of a continuous combined oestrogen/progestogen regimen for climacteric complaints. Maturitas 1982:4:95–102
   PubMed Web of Science ®Google Scholar
• Archer DF, Pickar JH. Hormone replacement therapy: effect of progestin dose and time since menopause on endometrial bleeding. Obstet Gynecol 2000;96:899–905
   PubMed Web of Science ®Google Scholar
• Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study. Am J Obstet Gynecol 1994;170: 1213–23
   PubMed Web of Science ®Google Scholar
• Wells M, Ulrich LG, Sturdee DW, et al. Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy; follow-up study. BMJ 2002; 325:239–42
   PubMed Web of Science ®Google Scholar
• Anderson GL, Judd HL, Kaunitz AM, et al., for the Women's Health Initiative Investigators. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. JAMA 2003;290:1739–48
   PubMed Web of Science ®Google Scholar
• Beral V, Bull D, Reeves G. Endometrial cancer and hormone replacement therapy in the Million Women Study. Lancet 2005; 365:1543–51
   PubMed Web of Science ®Google Scholar
• Notelowitz M, Lenihan JP, McDermott M, et al. Initial 17β- estradiol dose for treating menopausal symptoms. Obstet Gynecol 2000;95:726–31
   PubMed Web of Science ®Google Scholar
• Panay N, Ylikorkala O, Archer DF, et al. Ultra-low dose estradiol and norethisterone acetate: effective menopause symptom relief. Climacteric 2007;10:120–31
   PubMed Web of Science ®Google Scholar
• Sturdee DW, Archer DF, Rakov V, Lang E; CHOICE Study Investigators. Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women. Climacteric 2008;11:63–73
   PubMed Web of Science ®Google Scholar
• Bergeron C, Nogales FF, Rechberger T, et al. Ultra low dose continuous combined hormone replacement therapy with 0.5 mg 17β-estradiol and 2.5 mg dydrogesterone: protection of the endometrium and amenorrhoea rate. Maturitas 2010;66: 201–5
   PubMed Web of Science ®Google Scholar
• Stevenson JC, Durand G, Kahler E, Pertyński T. Oral ultra- low dose continuous combined hormone replacement therapy with 0.5 mg 17β-estradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: results from a double-blind, controlled study. Maturitas 2010;67:227–32
   PubMed Web of Science ®Google Scholar
• Riphagen FE. Intrauterine application of progestins in hormone replacement therapy. Climacteric 2000;3:199–211
   PubMedGoogle Scholar
• Hampton NR, Rees MC, Lowe DG, et al. Levonorgestrel intrauterine system (LNG-IUS) with conjugated oral equine estrogen: a successful regimen for HRT in perimenopausal women. Hum Reprod 2005;20:2653–60
   PubMed Web of Science ®Google Scholar
• Dören M, Schneider HP. The impact of different HRT regimens on compliance. Int J Fertil Menopausal Stud 1996;41: 29–39
   PubMed Web of Science ®Google Scholar
• Bakken K, Eggen AE, Lund E. Side-effects of hormone replacement therapy and influence on pattern of use among women aged 45–64 years. The Norwegian Women and Cancer (NOWAC) study 1997. Acta Obstet Scand 2004;83: 850–6
   Google Scholar
• Goldstein SR. The case for less-than-monthly progestogen in women on HT: is transvaginal ultrasound the key?Menopause 2005;12:110–13
   PubMed Web of Science ®Google Scholar
• Gompel A. Micronized progesterone and its impact on the endometrium and breast vs. progestogens. Climacteric 2012; 15(Suppl 1):18–25
   PubMed Web of Science ®Google Scholar
• Longacre TA, Barrow SA. A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 1986;10:382–93
   PubMed Web of Science ®Google Scholar
• Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine estrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet Oncol 2012;13:476–86
   PubMed Web of Science ®Google Scholar
• Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997;350:1047–59
   PubMed Web of Science ®Google Scholar
• Stanczyk FZ, Hapgood JP, Winer S, Mishell DR. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions and clinical effects. Endocrine Rev 2013;34:171–208
   PubMed Web of Science ®Google Scholar
• 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;107:103–11
   PubMed Web of Science ®Google Scholar
• Chlebowski RT, Manson JE, Anderson GL, et al. Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative observational study. J Natl Cancer Inst 2013;105:526–35
   PubMed Web of Science ®Google Scholar
• Lundström E, Bygdeson M, Svane G, et al. Neutral effect of ultra-low-dose continuous combined estradiol and norethisterone acetate on mammographic breast density. Climacteric 2007; 10:249–56
   PubMed Web of Science ®Google Scholar
• Marsden J. Hormone replacement therapy and breast disease. The Obstetrican & Gynaecologist 2010;12:155–62
   Google Scholar
• Lyytinen HK, Dyba T, Pukkala E, Ylikorkala O. A case-control study on hormone therapy as a risk for breast cancer in Finland. Intrauterine system carries a risk as well. Int J Cancer 2010; 126:483–9
   PubMed Web of Science ®Google Scholar
• Pinkerton JV, Pickar JH, Racketa J, Mirkin S. Bazedoxifene/ conjugated estrogens for menopausal symptom treatment and osteoporosis prevention. Climacteric 2012;15:411–18
   PubMed Web of Science ®Google Scholar
• Grady D, Gebretsadik T, Kerlikowski V, et al. Hormone replacement therapy and endometrial cancer risk; a meta-analysis. Obstet Gynecol 1995;85:304–13
   PubMed Web of Science ®Google Scholar