Skip to main content
Journal cover image

Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.

Publication ,  Journal Article
Hawkins Bressler, L; Fritz, MA; Wu, S-P; Yuan, L; Kafer, S; Wang, T; DeMayo, FJ; Young, SL
Published in: J Clin Endocrinol Metab
August 18, 2021

CONTEXT: Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene. OBJECTIVE: To examine cellular and molecular differences in the endometrium of women with suboptimal vs optimal endometrial thickening following clomiphene. METHODS: Translational prospective cohort study from 2018 to 2020 at a university-affiliated clinic. Reproductive age women with unexplained infertility treated with 100 mg of clomiphene on cycle days 3 to 7 who developed optimal (≥8mm; n = 6, controls) or suboptimal (<6mm; n = 7, subjects) endometrial thickness underwent preovulatory blood and endometrial sampling. The main outcome measures were endometrial tissue architecture, abundance and location of specific proteins, RNA expression, and estrogen receptor (ER) α binding. RESULTS: The endometrium of suboptimal subjects compared with optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%, P = .01), decreased immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), increased immunostaining of pan-leukocyte marker CD45 and ERβ, but decreased ERα immunostaining (all P < .05). RNA-seq identified 398 differentially expressed genes between groups. Pathway analysis of differentially expressed genes indicated reduced proliferation (Z-score = -2.2, P < .01), decreased angiogenesis (Z-score = -2.87, P < .001), increased inflammation (Z-score = +2.2, P < .01), and ERβ activation (Z-score = +1.6, P < .001) in suboptimal subjects. ChIP-seq identified 6 genes bound by ERα that were differentially expressed between groups (P < .01), some of which may play a role in implantation. CONCLUSION: Women with suboptimal endometrial thickness after clomiphene exhibit aberrant ER expression patterns, architectural changes, and altered gene and protein expression suggesting reduced proliferation and angiogenesis in the setting of increased inflammation.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

August 18, 2021

Volume

106

Issue

9

Start / End Page

2547 / 2565

Location

United States

Related Subject Headings

  • Receptors, Estrogen
  • Humans
  • Gonadal Steroid Hormones
  • Female
  • Estrogens
  • Endometrium
  • Endocrinology & Metabolism
  • Clomiphene
  • Cell Proliferation
  • Adult
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hawkins Bressler, L., Fritz, M. A., Wu, S.-P., Yuan, L., Kafer, S., Wang, T., … Young, S. L. (2021). Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action. J Clin Endocrinol Metab, 106(9), 2547–2565. https://doi.org/10.1210/clinem/dgab381
Hawkins Bressler, Leah, Marc A. Fritz, San-Pin Wu, Lingwen Yuan, Suzanna Kafer, Tianyuan Wang, Francesco J. DeMayo, and Steven L. Young. “Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.J Clin Endocrinol Metab 106, no. 9 (August 18, 2021): 2547–65. https://doi.org/10.1210/clinem/dgab381.
Hawkins Bressler L, Fritz MA, Wu S-P, Yuan L, Kafer S, Wang T, et al. Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action. J Clin Endocrinol Metab. 2021 Aug 18;106(9):2547–65.
Hawkins Bressler, Leah, et al. “Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.J Clin Endocrinol Metab, vol. 106, no. 9, Aug. 2021, pp. 2547–65. Pubmed, doi:10.1210/clinem/dgab381.
Hawkins Bressler L, Fritz MA, Wu S-P, Yuan L, Kafer S, Wang T, DeMayo FJ, Young SL. Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action. J Clin Endocrinol Metab. 2021 Aug 18;106(9):2547–2565.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

August 18, 2021

Volume

106

Issue

9

Start / End Page

2547 / 2565

Location

United States

Related Subject Headings

  • Receptors, Estrogen
  • Humans
  • Gonadal Steroid Hormones
  • Female
  • Estrogens
  • Endometrium
  • Endocrinology & Metabolism
  • Clomiphene
  • Cell Proliferation
  • Adult