Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women

Judd, Howard L.; Legault, Claudine; Wasilauskas, Carol H.; Merino, María J.; Barrett‐Connor, Elizabeth; Trabal, Jose; Miller, Vincent; Barnabei, Vanessa M.; Levin, Ginny; Bush, Trudy L.; Foster, David A.; Zacur, Howard; Woodruff, J. Donald; Stefanick, Marcia L.; Wood, Peter D.; Akana, Allison; Heinrichs, Wm. LeRoy; O’Hanlan, Katherine A.; Buyalos, Richard P.; Greendale, Gail A.; Lozano, Kathy; Carrion-Petersen, Mary Lou; Cavero, Carmella; Langer, Róbert; Schrott, Helmut G.; Benda, Jo Ann; deProsse, Charles; Fedderson, Deborah; Johnson, Susan R.; Pauerstein, Carl J.; Ahmad, Mohammad M.; Brown, Herbert P.; Schenken, Robert S.; Rodriguez-Sifuentes, Mercedes; Valente, Philip T.; Espeland, Mark A.; Wells, H. Bradley; Lane, Kathy; Mebane-Sims, Irma; Kelaghan, Joseph; McGowan, Joan A.; Fradkin, Judith; Sherman, Sheryl S.; Scully, Robert E.

doi:10.1001/jama.1996.03530290040035

Cited by 478 publications

(20 citation statements)

References 24 publications

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“…If MP is being used as part of ccMHT or scMHT, short-term use for ≤5 years is recommended. In addition, care should be taken that ccMHT is used instead of scMHT with an adequate dosage of at least 200 mg/day based on the results of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial [37].…”

Section: Discussionmentioning

confidence: 99%

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review

Tempfer

Hilal

Kern

et al. 2020

Cancers

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Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. Results: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. Conclusion: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.

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Section: Discussionmentioning

confidence: 99%

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review

Tempfer

Hilal

Kern

et al. 2020

Cancers

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“…For such women, our current findings suggest that it would be prudent to monitor bone density during treatment and to begin antiosteoporosis therapy if decreases in bone density are detected. Also, estrogen administration has been shown to have a beneficial effect on serum lipids, (27) and, in principle, letrozole therapy could have adverse effects. Therefore, it was reassuring that we found no significant effects of treatment on serum lipids over the 6‐month duration of our study.…”

Section: Discussionmentioning

confidence: 99%

Role of Low Levels of Endogenous Estrogen in Regulation of Bone Resorption in Late Postmenopausal Women

Heshmati

Khosla

Robins³

et al. 2002

Journal of Bone and Mineral Research

185

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Although median levels of bone turnover are increased in postmenopausal women, it is unclear whether the low circulating levels of endogenous estrogen exert a regulatory role on these levels. This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age ؎ SD, 69 ؎ 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months. Letrozole treatment reduced serum estrone (E 1 ) and estradiol (E 2 ) to near undetectable levels ( p < 0.

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“…However, estrogen‐only therapy alone increases the incidence of endometrial cancer by a factor of 2−10 times over the baseline rate of 1:1000 in untreated women per year. In the postmenopausal estrogen–progestin intervention trials, combined E + P therapy led to marked reductions in the incidence of atypical hyperplasia (0% versus 11.8%) compared with estrogen only . Adequate cyclic progestin of at least 12 days/month may be as effective as continuous low‐dose daily progestin.…”

Section: Opportunitymentioning

confidence: 99%

Aging, the menopausal transition, and hormone replenishment therapy: retrieval of confidence and compliance

Saul

Kase

2018

Annals of the New York Academy of Sciences

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The negative health consequences of age and the postmenopausal hypoestrogenic state and their clinical management are described in this paper. While some dysfunctional elements are irreversibly entrained, others can be modified by an updated menopausal hormone therapy (MHT) strategy reflecting revision and reassessment of the initial Women's Health Initiative (WHI) reports. However, until that positive outcome is realized, menopausal women and their healthcare providers must re-establish willingness to utilize these effective strategies. This reluctance is fueled by persistent mistaken application of WHI results that reflect the bundled risk and benefits of MHT in asymptomatic women aged 50-79 (average age 63), as opposed to women in their 40s and 50s who initiate therapy because of vasomotor symptoms. The absolute risk of adverse outcomes is much lower and the benefits dramatically higher in these younger women. In addition, newer FDA-approved formulations, lower dosage regimens, and transdermal delivery methodologies offer wider choice of approaches and promise even greater safety. The positive and negative lessons of the WHI have been learned and can be applied effectively.

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Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women

Cited by 478 publications

References 24 publications

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review

Role of Low Levels of Endogenous Estrogen in Regulation of Bone Resorption in Late Postmenopausal Women

Aging, the menopausal transition, and hormone replenishment therapy: retrieval of confidence and compliance

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