Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Endocrinological Investigation
Published in: Journal of Endocrinological Investigation 3/2023

Open Access 01-03-2023 | Endometrial Cancer | Review

Androgens in endometrial carcinoma: the killer or helper?

Authors: X. Wu, K. Zhang, X. Zhong, X. Huo, J. Zhang, W. Tian, X. Yang, Y. Zhang, Y. Wang

Published in: Journal of Endocrinological Investigation | Issue 3/2023

Login to get access

Abstract

Purpose

The aim of this review is to discuss the role of androgens in the progression of endometrial carcinoma (EC) with particular focus on the different kinds of androgenic hormones, androgen receptor (AR) and intracrine androgen metabolism.

Methods

A comprehensive literature search within PubMed was performed. Selected publications related to androgens and EC were reviewed.

Results

There are different kinds of androgenic hormones, and different kinds of androgens may have different effects. Elevated androgens (especially testosterone) have been associated with an increased EC risk in postmenopausal women. 5α-reductases (5α-Reds) and 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) pathway may inhibit the progression of EC mediated by dihydrotestosterone (DHT), but aromatases stimulate further progression of EC. The most of studies accessing the prognostic value of AR have found that AR expression may be a favorable prognostic indicator.

Conclusion

Androgens may have both oncogenic and tumor suppressive roles. Androgen-specific biases in metabolism and the expression of AR may contribute to the different prognosis of patients with EC.
Literature
1.
Siegel RL, Miller KD, Fuchs HE et al (2021) Cancer statistics. Cancer J Clin 71(1):7–33CrossRef
2.
Simpson E, Rubin G, Clyne C et al (2000) The role of local estrogen biosynthesis in males and females. Trends Endocrinol Metab 11(5):184–188PubMedCrossRef
3.
4.
Lukanova A, Lundin E, Micheli A et al (2004) Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108(3):425–432PubMedCrossRef
5.
Michels KA, Brinton LA, Wentzensen N et al (2019) Postmenopausal androgen metabolism and endometrial cancer risk in the women’s health initiative observational study. JNCI cancer spectrum. 3(3):pkz029PubMedPubMedCentralCrossRef
6.
Audet-Walsh E, Lépine J, Grégoire J et al (2011) Profiling of endogenous estrogens, their precursors, and metabolites in endometrial cancer patients: association with risk and relationship to clinical characteristics. J Clin Endocrinol Metab 96(2):E330–E339PubMedCrossRef
7.
Annekatrin L, Eva L, Andrea M et al (2004) Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108(3):425CrossRef
8.
Islam RM, Bell RJ, Green S et al (2019) Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol 7(10):754–766PubMedCrossRef
9.
Grimstad FW, Fowler KG, New EP et al (2018) Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series. Am J Obstet Gynecol 220(3):257
10.
Bentz EK, Pils D, Bilban M et al (2010) Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals. Fertil Steril 94(7):2688–2696PubMedCrossRef
11.
Giorgi EP, Stein WD (1981) The transport of steroids into animal cells in culture. Endocrinology 108(2):688–697PubMedCrossRef
12.
Schiffer L, Arlt W, Storbeck KH (2018) Intracrine androgen biosynthesis, metabolism and action revisited. Mol Cell Endocrinol 15(465):4–26CrossRef
13.
14.
15.
Cornel KMC, Delvoux B, Saya T et al (2018) The sulfatase pathway as estrogen supply in endometrial cancer. Steroids 139:45–52PubMedCrossRef
16.
Cornel KM, Krakstad C, Delvoux B et al (2017) High mRNA levels of 17β-hydroxysteroid dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol 15(442):51–57CrossRef
17.
Utsunomiya H, Ito K, Suzuki T et al (2004) Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma. Clin Cancer Res 10(17):5850–5856PubMedCrossRef
18.
Sinreih M, Hevir N, Rižner TL (2013) Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer. Chem-Biol Interact 202(1–3):210PubMedCrossRef
19.
Cornel KM, Kruitwagen RF, Delvoux B et al (2012) Overexpression of 17beta-hydroxysteroid dehydrogenase type 1 increases the exposure of endometrial cancer to 17beta-estradiol. J Clin Endocrinol Metab 97(4):E591-601PubMedCrossRef
20.
Konings GF, Cornel KM, Xanthoulea S et al (2018) Blocking 17beta-hydroxysteroid dehydrogenase type 1 in endometrial cancer: a potential novel endocrine therapeutic approach. J Pathol 244(2):203–214PubMedCrossRef
21.
Zhu Y, Shen J, Gao L et al (2016) Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway. Oncol Rep 35(4):2391–2397PubMedCrossRef
22.
Zhang Z, Zhou D, Lai Y et al (2012) Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways. Cancer Lett 319(1):89–97PubMedCrossRef
23.
Lépine J, Audet-Walsh E, Grégoire J et al (2010) Circulating estrogens in endometrial cancer cases and their relationship with tissular expression of key estrogen biosynthesis and metabolic pathways. J Clin Endocrinol Metab 95(6):2689–2698PubMedCrossRef
24.
Chiaki H, Yasuhiro M, Sota T et al (2018) 17β-Hydroxysteroid dehydrogenase type 2 expression is induced by androgen signaling in endometrial cancer. Int J Mol Sci 19(4):1139CrossRef
25.
Hojnik M, Kenda Šuster N, Smrkolj Š et al (2020) AKR1C3 is associated with better survival of patients with endometrial carcinomas. J Clini Med 9(12):4105CrossRef
26.
Tanaka S, Miki Y, Hashimoto C et al (2015) The role of 5α-reductase type 1 associated with intratumoral dihydrotestosterone concentrations in human endometrial carcinoma. Mol Cell Endocrinol 5(401):56–64CrossRef
27.
Sinreih M, Hevir N, Rižner TL (2013) Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer. Chem Biol Interact 202(1–3):210–217PubMedCrossRef
28.
Ito K, Suzuki T, Akahira J et al (2002) Expression of androgen receptor and 5alpha-reductases in the human normal endometrium and its disorders. Int J Cancer 99(5):652–657PubMedCrossRef
29.
Wasniewski T, Woclawek-Potocka I (2018) Altered expression of lysophosphatidic acid receptors, in association with the synthesis of estrogens and androgens in type 1 endometrial cancer biology. Gynecol Endocrinol 34(5):422–427PubMedCrossRef
30.
Wang ZH, Zhang YZ, Wang YS et al (2019) Identification of novel cell glycolysis related gene signature predicting survival in patients with endometrial cancer. Cancer Cell Int 19:296PubMedPubMedCentralCrossRef
31.
Hashimoto C, Miki Y, Tanaka S et al (2018) 17beta-Hydroxysteroid dehydrogenase type 2 expression is induced by androgen signaling in endometrial cancer. Int J Mol Sci 19(4):1139PubMedPubMedCentralCrossRef
32.
Kazmierczak W, Skalba P, Dabkowska-Huc A et al (2006) Expression of aromatase and 5-alpha-reductase genes in endometrial adenocarcinoma. Pathol Res Pract 202(11):789–791PubMedCrossRef
33.
Simitsidellis I, Saunders PTK, Gibson DA (2018) Androgens and endometrium: new insights and new targets. Mol Cell Endocrinol 15(465):48–60CrossRef
34.
Younas K, Quintela M, Thomas S et al (2019) Delayed endometrial decidualisation in polycystic ovary syndrome; the role of AR-MAGEA11. J Mol Med 97(9):1315–1327PubMedCrossRef
35.
Wang T, Zhang J, Hu M et al (2019) Differential expression patterns of glycolytic enzymes and mitochondria-dependent apoptosis in PCOS patients with endometrial hyperplasia, an early hallmark of endometrial cancer, in vivo and the impact of metformin in vitro. Int J Biol Sci 15(3):714–725PubMedPubMedCentralCrossRef
36.
Cloke B, Christian M (2012) The role of androgens and the androgen receptor in cycling endometrium. Mol Cell Endocrinol 358(2):166–175PubMedCrossRef
37.
Zadeh SL, Duska LR, Mills AM (2018) Androgen receptor expression in endometrial carcinoma. Int J Gynecol Pathol 37(2):167–173PubMedCrossRef
38.
Koivisto-Korander R, Butzow R, Koivisto AM et al (2011) Immunohistochemical studies on uterine carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma: expression and prognostic importance of ten different markers. Tumour Biol 32(3):451–459PubMedCrossRef
39.
Hashmi AA, Hussain ZF, Qadri A et al (2018) Androgen receptor expression in endometrial carcinoma and its correlation with clinicopathologic features. BMC Res Notes 11(1):289PubMedPubMedCentralCrossRef
40.
Cao J, Hacking S, Chavarria-Bernal HD et al (2021) Androgen receptor immunohistochemical expression in undifferentiated/dedifferentiated endometrial carcinoma. Int J Gynecol Pathol 41(1):28–34 (Publish Ahead of Print)CrossRef
41.
Kamal AM, Bulmer JN, DeCruze SB et al (2016) Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival. Br J Cancer 114(6):688–696PubMedPubMedCentralCrossRef
42.
Tangen IL, Onyango TB, Kopperud R et al (2016) Androgen receptor as potential therapeutic target in metastatic endometrial cancer. Oncotarget 7(31):49289–49298PubMedPubMedCentralCrossRef
43.
Mahdi Z, Abdulfatah E, Pardeshi V et al (2017) The impact of androgen receptor expression on endometrial carcinoma recurrence and survival. Int J Gynecol Pathol 36(5):405–411PubMedCrossRef
44.
Koivisto CS, Parrish M, Bonala SB et al (2020) Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma. Neoplasia 22(10):484–496PubMedPubMedCentralCrossRef
45.
Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666–3672PubMedCrossRef
46.
Mullee A, Dimou N, Allen N et al (2021) Testosterone, sex hormone-binding globulin, insulin-like growth factor-1 and endometrial cancer risk: observational and Mendelian randomization analyses. Br J Cancer 125(9):1308–1317PubMedPubMedCentralCrossRef
47.
Farhat GN, Cummings SR, Chlebowski RT et al (2011) Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst 103(7):562–570PubMedPubMedCentralCrossRef
48.
Teng F, Ma X, Yu X et al (2020) High serum androgen and insulin concentrations increase the tendency of endometrial carcinoma. J Cancer 11(19):5656–5664PubMedPubMedCentralCrossRef
49.
50.
de Zegher F, Lopez-Bermejo A, Ibáñez L (2009) Adipose tissue expandability and the early origins of PCOS. Trends Endocrinol Metab 20(9):418–423PubMedCrossRef
51.
52.
53.
Borghi C, Indraccolo U, Scutiero G et al (2018) Biomolecular basis related to inflammation in the pathogenesis of endometrial cancer. Eur Rev Med Pharmacol Sci 22(19):6294–6299PubMed
54.
Maseroli E, Cellai I, Filippi S et al (2020) Anti-inflammatory effects of androgens in the human vagina. J Mol Endocrinol 65(3):109–124PubMedCrossRef
55.
56.
Allen NE, Key TJ, Dossus L et al (2008) Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 15(2):485–497PubMedPubMedCentralCrossRef
57.
Clendenen TV, Hertzmark K, Koenig KL et al (2016) Premenopausal circulating androgens and risk of endometrial cancer: results of a prospective study. Hormones Cancer 7(3):178–187PubMedPubMedCentralCrossRef
58.
Cornel KMC, Krakstad C, Delvoux B et al (2017) High mRNA levels of 17β-hydroxysteroid dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol 442:51PubMedCrossRef
59.
Vladislav Z, Hsueh-Kung L, Joseph A et al (2010) Suppressed expression of type 2 3alpha/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in endometrial hyperplasia and carcinoma. Int J Clin Exp Pathol 3(6):608
60.
Hevir-Kene N, Rižner TL (2015) The endometrial cancer cell lines Ishikawa and HEC-1A, and the control cell line HIEEC, differ in expression of estrogen biosynthetic and metabolic genes, and in androstenedione and estrone-sulfate metabolism. Chem Biol Interact 5(234):309–319CrossRef
61.
Sinreih M, Anko M, Zukunft S et al (2015) Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines. Chem Biol Interact 5(234):297–308CrossRef
Metadata
Title
Androgens in endometrial carcinoma: the killer or helper?
Authors
X. Wu
K. Zhang
X. Zhong
X. Huo
J. Zhang
W. Tian
X. Yang
Y. Zhang
Y. Wang
Publication date
01-03-2023
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 3/2023
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-022-01916-1

Other articles of this Issue 3/2023

Journal of Endocrinological Investigation 3/2023 Go to the issue

Original Article

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure

Original Article

Favorable outcome in advanced pheochromocytoma and paraganglioma after hypofractionated intensity modulated radiotherapy

Original Article

Graves’ orbitopathy post-SARS-CoV-2 vaccines: report on six patients

Original Article

Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case–control study

Original Article

Predictors of postoperative biochemical remission in lower Knosp grade growth hormone-secreting pituitary adenomas: a large single center study

Original Article

Shared genetic architecture between type 2 diabetes and COVID-19 severity
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits