Aromatase and endometriosis

Serdar E. Bulun, Bulun Se, Zongjuan Fang, Fang Z, Gonca İmir, Imir G, Bilgin Gurates, Gurates B, Mitsutoshi Tamura, Tamura M, Yilmaz B, Bertan Yilmaz, Langoi D, David Langoi, Sanober Amin, Amin S, Sijun Yang, Yang S, Santanu Deb, Deb S
Seminars in reproductive medicine · 2004 · doi:10.1055/s-2004-823026 · PMID:15083380
review OA: closed public-domain-us ⤵ 1 in-corpus citation
Full text JSON View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Endometriosis tissue exhibits high aromatase enzyme activity, enabling local estrogen production that is further induced by prostaglandin E2, creating a cycle targeted by aromatase inhibitors.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This paper reviews and synthesizes evidence that aromatase (P450arom) is central to local estrogen biosynthesis in endometriosis tissue, noting that normal endometrium shows no detectable aromatase activity. It describes a positive feedback loop in which prostaglandin E2 strongly induces aromatase in endometriosis, while estrogen increases cyclo-oxygenase-2 and thereby prostaglandin E2 production, and reports that aromatase inhibitors can target this cycle, with pilot trials showing decreased pelvic pain. A stated limitation is that the therapeutic support is based on pilot trials rather than definitive studies, and the evidence discussed spans mechanistic observations and prior work rather than a single large experimental program. This paper is centrally about endometriosis — it focuses on aromatase-driven local estrogen production and a PGE2–estrogen–COX-2 feedback mechanism, linking these pathways to pelvic pain and inhibition by aromatase inhibitors.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Aromatase p450 (p450arom) is the key enzyme for biosynthesis of estrogen, which is an essential hormone for the establishment and growth of endometriosis. There is no detectable aromatase enzyme activity in normal endometrium; therefore, estrogen is not locally produced in endometrium. Endometriosis tissue, however, contains very high levels of aromatase enzyme, which leads to production of significant quantities of estrogen. Moreover, one of the best-known mediators of inflammation and pain, prostaglandin E (2), strikingly induces aromatase enzyme activity and formation of local estrogen in this tissue. Additionally, estrogen itself stimulates cyclo-oxygenase-2 and therefore increases the formation of prostaglandin E (2) in endometriosis. We were able to target this positive feedback cycle in endometriosis using aromatase inhibitors. In fact, pilot trials showed that aromatase inhibitors could decrease pelvic pain associated with endometriosis.
Full text 7,367 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Keywords

Aromatase - aromatase inhibitor - endometriosis - endometrium - estrogen biosynthesis - pelvic pain

References

- 1 Vessey M P, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ. 1993; 306 182-184 - 2 Kjerulff K H, Erickson B A, Langenberg P W. Chronic gynecological conditions reported by US women: findings from the National Health Information Survey, 1984 to 1992. Am J Public Health. 1996; 86 195-199 - 3 Olive D L, Schwartz L B. Endometriosis. N Engl J Med. 1993; 328 1759-1769 - 4 Sampson J A. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927; 14 422-425 - 5 Halme J, White C, Kauma S, Estes J, Haskill S. Peritoneal macrophages from patients with endometriosis release growth factor activity in vitro. J Clin Endocrinol Metab. 1988; 66 1044-1049 - 6 Noble L S, Simpson E R, Johns A, Bulun S E. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996; 81 174-179 - 7 Zeitoun K, Takayama K, Michael M D, Bulun S E. Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of SF-1 and COUP-TF to the same cis-acting element. Mol Endocrinol. 1999; 13 239-253 - 8 Khorram O, Taylor R N, Ryan I P, Schall T J, Landers D V. Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis. Am J Obstet Gynecol. 1993; 169 1545-1549 - 9 Sharpe-Timms K L, Penney L L, Zimmer R L, Wright J A, Zhang Y, Surewicz K. Partial purification and amino acid sequence analysis of endometriosis protein-II (ENDO-II) reveals homology with tissue inhibitor of metalloproteinases-1 (TIMP-1). J Clin Endocrinol Metab. 1995; 80 3784-3787 - 10 Bruner K L, Matrisian L M, Rodgers W H, Gorstein F, Osteen K G. Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice. J Clin Invest. 1997; 99 2851-2857 - 11 Osteen K G, Bruner K L, Sharpe-Timms K L. Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis. Semin Reprod Endocrinol. 1996; 14 247-255 - 12 Zeitoun K, Takayama K, Sasano H et al.. Deficient 17β-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize estradiol-17β. J Clin Endocrinol Metab. 1998; 83 4474-4480 - 13 Michael M D, Michael L F, Simpson E R. A CRE-like sequence that binds CREB and contributes to cAMP-dependent regulation of the proximal promoter of the human aromatase P450 (CYP19) gene. Mol Cell Endocrinol. 1997; 134 147-156 - 14 Michael M D, Kilgore M W, Morohashi K I, Simpson E R. Ad4BP/SF-1 regulates cyclic AMP-induced transcription from the proximal promoter (PII) of the human aromatase P450 (CYP19) gene in the ovary. J Biol Chem. 1995; 270 13561-13566 - 15 Simpson E R, Mahendroo M S, Means G D et al.. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994; 15 342-355 - 16 Ackerman G E, Smith M E, Mendelson C R, MacDonald P C, Simpson E R. Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab. 1981; 53 412-417 - 17 MacDonald P C, Rombaut R P, Siiteri P K. Plasma precursors of estrogen, I: Extent of conversion of plasma Δ4-androstenedione to estrone in normal males and non-pregnant normal, castrate and adrenalectomized females. J Clin Endocrinol Metab. 1967; 27 1103-1111 - 18 MacDonald P C, Edman C D, Hemsell D L, Porter J C, Siiteri P K. Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am J Obstet Gynecol. 1978; 130 448-455 - 19 Bulun S E, Price T M, Mahendroo M S, Aitken J, Simpson E R. A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab. 1993; 77 1622-1628 - 20 Yue W, Wang J P, Hamilton C J, Demers L M, Santen R J. In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Res. 1998; 58 927-932 - 21 Bulun S E, Simpson E R, Word R A. Expression of the CYP19 gene and its product aromatase cytochrome P450 in human leiomyoma tissues and cells in culture. J Clin Endocrinol Metab. 1994; 78 736-743 - 22 Noble L S, Takayama K, Zeitoun K M et al.. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997; 82 600-606 - 23 Bulun S E, Mahendroo M S, Simpson E R. Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua. J Clin Endocrinol Metab. 1993; 76 1458-1463 - 24 Tamura M, Deb S, Sebastian S, Okamura K, Bulun S E. Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells. Fertil Steril. 2004; , In press - 25 Hill J A. Immunology and endometriosis. Fertil Steril. 1992; 58 262-264 - 26 Takayama K, Zeitoun K, Gunby R T, Sasano H, Carr B R, Bulun S E. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril. 1998; 69 709-713 - 27 Ailawadi R K, Jobanputra S, Kataria M, Gurates B, Bulun S E. Treatment of endometriosis and chronic pelvic pain with petrozole and norethindrone acetate: a pilot study. Fertil Steril. 2004; , In press - 28 Henzl M R, Corson S L, Moghissi K, Buttram V C, Berqvist C, Jacobson J. Administration of nasal nafarelin as compared with oral danazol for endometriosis. N Engl J Med. 1988; 318 485-489 - 29 Waller K G, Shaw R W. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril. 1993; 59 511-515 - 30 Metzger D A, Lessey B A, Soper J T, McCarty Jr K S, Haney A F. Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content. Obstet Gynecol. 1991; 78 946-950 Serdar E BulunM.D. Department of Obstetrics and Gynecology, Northwestern University 333 E. Superior Street, Suite 484, Chicago, IL 60611

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Aromatase Endometriosis Aromatase Endometriosis Endometriosis Enzyme Inhibitors Enzyme Inhibitors Estrogens Estrogens Female Gene Expression Regulation Humans Stromal Cells Stromal Cells

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cited by (2)

Cited by (2)

Source provenance

europepmc
last seen: 2026-08-06T06:07:45.168820+00:00
pubmed
last seen: 2026-05-13T22:12:38.158000+00:00
unpaywall
last seen: 2026-08-06T06:41:17.185923+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine