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Environ Health Perspect. Jun 2003; 111(8): 1037–1054.
PMCID: PMC1241553
Research Article

Etiology and pathogenesis of uterine leiomyomas: a review.

Abstract

Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Abraham S, Johnson CL. Prevalence of severe obesity in adults in the United States. Am J Clin Nutr. 1980 Feb;33(2 Suppl):364–369. [PubMed]
  • Adlercreutz H, Fotsis T, Heikkinen R, Dwyer JT, Woods M, Goldin BR, Gorbach SL. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet. 1982 Dec 11;2(8311):1295–1299. [PubMed]
  • Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997 Apr;29(2):95–120. [PubMed]
  • Aharoni A, Reiter A, Golan D, Paltiely Y, Sharf M. Patterns of growth of uterine leiomyomas during pregnancy. A prospective longitudinal study. Br J Obstet Gynaecol. 1988 May;95(5):510–513. [PubMed]
  • Alam NA, Bevan S, Churchman M, Barclay E, Barker K, Jaeger EE, Nelson HM, Healy E, Pembroke AC, Friedmann PS, et al. Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43. Am J Hum Genet. 2001 May;68(5):1264–1269. [PMC free article] [PubMed]
  • Albala JS, Thelen MP, Prange C, Fan W, Christensen M, Thompson LH, Lennon GG. Identification of a novel human RAD51 homolog, RAD51B. Genomics. 1997 Dec 15;46(3):476–479. [PubMed]
  • Amant F, Debiec-Rychter M, Schoenmakers EF, Hagemeijer-Hausman A, Vergote I. Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome. Genes Chromosomes Cancer. 2001 Dec;32(4):324–329. [PubMed]
  • Anania CA, Stewart EA, Quade BJ, Hill JA, Nowak RA. Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding. Mol Hum Reprod. 1997 Aug;3(8):685–691. [PubMed]
  • Andersen J. Factors in fibroid growth. Baillieres Clin Obstet Gynaecol. 1998 Jun;12(2):225–243. [PubMed]
  • Andersen J, Barbieri RL. Abnormal gene expression in uterine leiomyomas. J Soc Gynecol Investig. 1995 Sep-Oct;2(5):663–672. [PubMed]
  • Andersen J, DyReyes VM, Barbieri RL, Coachman DM, Miksicek RJ. Leiomyoma primary cultures have elevated transcriptional response to estrogen compared with autologous myometrial cultures. J Soc Gynecol Investig. 1995 May-Jun;2(3):542–551. [PubMed]
  • Arici A, Sozen I. Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil Steril. 2000 May;73(5):1006–1011. [PubMed]
  • Barbieri RL, McShane PM, Ryan KJ. Constituents of cigarette smoke inhibit human granulosa cell aromatase. Fertil Steril. 1986 Aug;46(2):232–236. [PubMed]
  • Baron JA, La Vecchia C, Levi F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol. 1990 Feb;162(2):502–514. [PubMed]
  • Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R. TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell. 1990 Nov 2;63(3):515–524. [PubMed]
  • Benassayag C, Leroy MJ, Rigourd V, Robert B, Honoré JC, Mignot TM, Vacher-Lavenu MC, Chapron C, Ferré F. Estrogen receptors (ERalpha/ERbeta) in normal and pathological growth of the human myometrium: pregnancy and leiomyoma. Am J Physiol. 1999 Jun;276(6 Pt 1):E1112–E1118. [PubMed]
  • Bigsby RM, Caperell-Grant A, Madhukar BV. Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice. Cancer Res. 1997 Mar 1;57(5):865–869. [PubMed]
  • Boehm KD, Daimon M, Gorodeski IG, Sheean LA, Utian WH, Ilan J. Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues. Mol Reprod Dev. 1990 Oct;27(2):93–101. [PubMed]
  • Boudouris O, Ferrand S, Guillet JL, Madelenat P. Effets paradoxaux du tamoxifène sur l'utérus de la femme. A propos de sept cas de myomes apparus sous traitement anti-estrogénique. J Gynecol Obstet Biol Reprod (Paris) 1989;18(3):372–378. [PubMed]
  • Brandon DD, Bethea CL, Strawn EY, Novy MJ, Burry KA, Harrington MS, Erickson TE, Warner C, Keenan EJ, Clinton GM. Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas. Am J Obstet Gynecol. 1993 Jul;169(1):78–85. [PubMed]
  • Brandon DD, Erickson TE, Keenan EJ, Strawn EY, Novy MJ, Burry KA, Warner C, Clinton GM. Estrogen receptor gene expression in human uterine leiomyomata. J Clin Endocrinol Metab. 1995 Jun;80(6):1876–1881. [PubMed]
  • Brosens I, Deprest J, Dal Cin P, Van den Berghe H. Clinical significance of cytogenetic abnormalities in uterine myomas. Fertil Steril. 1998 Feb;69(2):232–235. [PubMed]
  • Brown LF, Detmar M, Tognazzi K, Abu-Jawdeh G, Iruela-Arispe ML. Uterine smooth muscle cells express functional receptors (flt-1 and KDR) for vascular permeability factor/vascular endothelial growth factor. Lab Invest. 1997 Feb;76(2):245–255. [PubMed]
  • Büchi KA, Keller PJ. Cytoplasmic progestin receptors in myomal and myometrial tissues. Concentrations and hormonal dependency. Acta Obstet Gynecol Scand. 1983;62(5):487–492. [PubMed]
  • Buttram VC., Jr Uterine leiomyomata--aetiology, symptomatology and management. Prog Clin Biol Res. 1986;225:275–296. [PubMed]
  • Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, Roark M, Steinkampf MP. An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial. J Clin Endocrinol Metab. 1993 May;76(5):1217–1223. [PubMed]
  • Cassidenti DL, Pike MC, Vijod AG, Stanczyk FZ, Lobo RA. A reevaluation of estrogen status in postmenopausal women who smoke. Am J Obstet Gynecol. 1992 May;166(5):1444–1448. [PubMed]
  • Cecil HC, Bitman J, Harris SJ. Estrogenicity of o,p'-DDT in rats. J Agric Food Chem. 1971 Jan-Feb;19(1):61–65. [PubMed]
  • Chandrasekhar Y, Heiner J, Osuamkpe C, Nagamani M. Insulin-like growth factor I and II binding in human myometrium and leiomyomas. Am J Obstet Gynecol. 1992 Jan;166(1 Pt 1):64–69. [PubMed]
  • Charnock-Jones DS, Sharkey AM, Rajput-Williams J, Burch D, Schofield JP, Fountain SA, Boocock CA, Smith SK. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod. 1993 May;48(5):1120–1128. [PubMed]
  • Chegini N, Rao CV, Wakim N, Sanfilippo J. Binding of 125I-epidermal growth factor in human uterus. Cell Tissue Res. 1986;246(3):543–548. [PubMed]
  • Chegini N, Zhao Y, Williams RS, Flanders KC. Human uterine tissue throughout the menstrual cycle expresses transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and TGF beta type II receptor messenger ribonucleic acid and protein and contains [125I]TGF beta 1-binding sites. Endocrinology. 1994 Jul;135(1):439–449. [PubMed]
  • Chen L, Lindner HR, Lancet M. Mitogenic action of oestradiol-17 beta on human myometrial and endometrial cells in long-term tissue cultures. J Endocrinol. 1973 Oct;59(1):87–97. [PubMed]
  • Chiaffarino F, Parazzini F, La Vecchia C, Chatenoud L, Di Cintio E, Marsico S. Diet and uterine myomas. Obstet Gynecol. 1999 Sep;94(3):395–398. [PubMed]
  • Cohick WS, Clemmons DR. The insulin-like growth factors. Annu Rev Physiol. 1993;55:131–153. [PubMed]
  • Colacurci N, De Franciscis P, Cobellis L, Nazzaro G, De Placido G. Effects of hormone replacement therapy on postmenopausal uterine myoma. Maturitas. 2000 May 29;35(2):167–173. [PubMed]
  • Colgan TJ, Pendergast S, LeBlanc M. The histopathology of uterine leiomyomas following treatment with gonadotropin-releasing hormone analogues. Hum Pathol. 1993 Oct;24(10):1073–1077. [PubMed]
  • Cramer SF, Horiszny JA, Leppert P. Epidemiology of uterine leiomyomas. With an etiologic hypothesis. J Reprod Med. 1995 Aug;40(8):595–600. [PubMed]
  • Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol. 1990 Oct;94(4):435–438. [PubMed]
  • Cullinan-Bove K, Koos RD. Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology. 1993 Aug;133(2):829–837. [PubMed]
  • Daly DC, Walters CA, Prior JC, Kuslis ST, Chapitis J, Andreoli J, Riddick DH. Prolactin production from proliferative phase leiomyoma. Am J Obstet Gynecol. 1984 Apr 15;148(8):1059–1063. [PubMed]
  • Daniel M, Martin AD, Faiman C. Sex hormones and adipose tissue distribution in premenopausal cigarette smokers. Int J Obes Relat Metab Disord. 1992 Apr;16(4):245–254. [PubMed]
  • Dawood MY, Khan-Dawood FS. Plasma insulin-like growth factor-I, CA-125, estrogen, and progesterone in women with leiomyomas. Fertil Steril. 1994 Apr;61(4):617–621. [PubMed]
  • de Aloysio D, Altieri P, Penacchioni P, Salgarello M, Ventura V. Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT. Maturitas. 1998 Jun 17;29(3):261–264. [PubMed]
  • Debodinance P. Hystérectomies pour lésions bénignes sur utérus non prolabé: Epidémiologie et suites opératoires dans le Nord de la France. J Gynecol Obstet Biol Reprod (Paris) 2001 Apr;30(2):151–159. [PubMed]
  • Deligdisch L. Hormonal pathology of the endometrium. Mod Pathol. 2000 Mar;13(3):285–294. [PubMed]
  • Dilts PV, Jr, Hopkins MP, Chang AE, Cody RL. Rapid growth of leiomyoma in patient receiving tamoxifen. Am J Obstet Gynecol. 1992 Jan;166(1 Pt 1):167–168. [PubMed]
  • Dixon Darlene, Flake Gordon P, Moore Alicia B, He Hong, Haseman Joseph K, Risinger John I, Lancaster Johnathan M, Berchuck Andrew, Barrett J Carl, Robboy Stanley J. Cell proliferation and apoptosis in human uterine leiomyomas and myometria. Virchows Arch. 2002 Jul;441(1):53–62. [PubMed]
  • Dixon D, He H, Haseman JK. Immunohistochemical localization of growth factors and their receptors in uterine leiomyomas and matched myometrium. Environ Health Perspect. 2000 Oct;108 (Suppl 5):795–802. [PubMed]
  • Eiletz J, Genz T, Pollow K, Schmidt-Gollwitzer M. Sex steroid levels in serum, myometrium, and fibromyomata in correlation with cytoplasmic receptors and 17 beta-HSD activity in different age-groups and phases of the menstrual cycle. Arch Gynecol. 1980 Jan;229(1):13–28. [PubMed]
  • Englund K, Blanck A, Gustavsson I, Lundkvist U, Sjöblom P, Norgren A, Lindblom B. Sex steroid receptors in human myometrium and fibroids: changes during the menstrual cycle and gonadotropin-releasing hormone treatment. J Clin Endocrinol Metab. 1998 Nov;83(11):4092–4096. [PubMed]
  • Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997 Dec;82(12):4258–4265. [PubMed]
  • Ezem BU, Otubu JA. Hysterectomy in the Hausa/Fulani population in Nigeria. Int J Gynaecol Obstet. 1981 Apr;19(2):145–148. [PubMed]
  • Fayed YM, Tsibris JC, Langenberg PW, Robertson AL., Jr Human uterine leiomyoma cells: binding and growth responses to epidermal growth factor, platelet-derived growth factor, and insulin. Lab Invest. 1989 Jan;60(1):30–37. [PubMed]
  • Fedele L, Bianchi S, Raffaelli R, Zanconato G. A randomized study of the effects of tibolone and transdermal estrogen replacement therapy in postmenopausal women with uterine myomas. Eur J Obstet Gynecol Reprod Biol. 2000 Jan;88(1):91–94. [PubMed]
  • Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992 Feb;13(1):18–32. [PubMed]
  • Fey MF, Peter HJ, Hinds HL, Zimmermann A, Liechti-Gallati S, Gerber H, Studer H, Tobler A. Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X chromosomal probe. J Clin Invest. 1992 May;89(5):1438–1444. [PMC free article] [PubMed]
  • FISHER WC, HELWIG EB. LEIOMYOMAS OF THE SKIN. Arch Dermatol. 1963 Nov;88:510–520. [PubMed]
  • Folkerd EJ, Newton CJ, Davidson K, Anderson MC, James VH. Aromatase activity in uterine leiomyomata. J Steroid Biochem. 1984 May;20(5):1195–1200. [PubMed]
  • Fraser HM. LHRH analogues: their clinical physiology and delivery systems. Baillieres Clin Obstet Gynaecol. 1988 Sep;2(3):639–658. [PubMed]
  • Friedman AJ, Barbieri RL, Doubilet PM, Fine C, Schiff I. A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertil Steril. 1988 Mar;49(3):404–409. [PubMed]
  • Friedman AJ, Harrison-Atlas D, Barbieri RL, Benacerraf B, Gleason R, Schiff I. A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata. Fertil Steril. 1989 Feb;51(2):251–256. [PubMed]
  • Friedman AJ, Lobel SM, Rein MS, Barbieri RL. Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis. Am J Obstet Gynecol. 1990 Oct;163(4 Pt 1):1114–1119. [PubMed]
  • Frigo P, Eppel W, Asseryanis E, Sator M, Golaszewski T, Gruber D, Lang C, Huber J. The effects of hormone substitution in depot form on the uterus in a group of 50 perimenopausal women--a vaginosonographic study. Maturitas. 1995 Apr;21(3):221–225. [PubMed]
  • Frisch RE, Wyshak G, Albright NL, Albright TE, Schiff I, Jones KP, Witschi J, Shiang E, Koff E, Marguglio M. Lower prevalence of breast cancer and cancers of the reproductive system among former college athletes compared to non-athletes. Br J Cancer. 1985 Dec;52(6):885–891. [PMC free article] [PubMed]
  • Fuchs-Young R, Howe S, Hale L, Miles R, Walker C. Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators. Mol Carcinog. 1996 Nov;17(3):151–159. [PubMed]
  • Fujimoto J, Hori M, Ichigo S, Tamaya T. Ovarian steroids regulate the expression of basic fibroblast growth factor and its mRNA in fibroblasts derived from uterine endometrium. Ann Clin Biochem. 1997 Jan;34(Pt 1):91–96. [PubMed]
  • Gambone JC, Reiter RC, Lench JB, Moore JG. The impact of a quality assurance process on the frequency and confirmation rate of hysterectomy. Am J Obstet Gynecol. 1990 Aug;163(2):545–550. [PubMed]
  • Gattas GJ, Quade BJ, Nowak RA, Morton CC. HMGIC expression in human adult and fetal tissues and in uterine leiomyomata. Genes Chromosomes Cancer. 1999 Aug;25(4):316–322. [PubMed]
  • Ginsburg J, Prelevic GM. Lack of significant hormonal effects and controlled trials of phyto-oestrogens. Lancet. 2000 Jan 15;355(9199):163–164. [PubMed]
  • Giudice LC, Irwin JC, Dsupin BA, Pannier EM, Jin IH, Vu TH, Hoffman AR. Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Hum Reprod. 1993 Nov;8(11):1796–1806. [PubMed]
  • Glass AR. Endocrine aspects of obesity. Med Clin North Am. 1989 Jan;73(1):139–160. [PubMed]
  • Gloudemans T, Prinsen I, Van Unnik JA, Lips CJ, Den Otter W, Sussenbach JS. Insulin-like growth factor gene expression in human smooth muscle tumors. Cancer Res. 1990 Oct 15;50(20):6689–6695. [PubMed]
  • Goldin BR, Adlercreutz H, Gorbach SL, Warram JH, Dwyer JT, Swenson L, Woods MN. Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women. N Engl J Med. 1982 Dec 16;307(25):1542–1547. [PubMed]
  • Goldzieher JW, Maqueo M, Ricaud L, Aguilar JA, Canales E. Induction of degenerative changes in uterine myomas by high-dosage progestin therapy. Am J Obstet Gynecol. 1966 Dec 15;96(8):1078–1087. [PubMed]
  • Gorbach SL, Goldin BR. Diet and the excretion and enterohepatic cycling of estrogens. Prev Med. 1987 Jul;16(4):525–531. [PubMed]
  • Goto F, Goto K, Weindel K, Folkman J. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest. 1993 Nov;69(5):508–517. [PubMed]
  • Gross KL, Morton CC. Genetics and the development of fibroids. Clin Obstet Gynecol. 2001 Jun;44(2):335–349. [PubMed]
  • Hall JM, Couse JF, Korach KS. The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem. 2001 Oct 5;276(40):36869–36872. [PubMed]
  • Haney AF. Clinical decision making regarding leiomyomata: what we need in the next millenium. Environ Health Perspect. 2000 Oct;108 (Suppl 5):835–839. [PubMed]
  • Harrison-Woolrych ML, Charnock-Jones DS, Smith SK. Quantification of messenger ribonucleic acid for epidermal growth factor in human myometrium and leiomyomata using reverse transcriptase polymerase chain reaction. J Clin Endocrinol Metab. 1994 May;78(5):1179–1184. [PubMed]
  • Harrison-Woolrych ML, Sharkey AM, Charnock-Jones DS, Smith SK. Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol Metab. 1995 Jun;80(6):1853–1858. [PubMed]
  • Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T, Sawada M, Noguchi S, Saji F. Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene. Gynecol Obstet Invest. 1995;40(3):204–208. [PubMed]
  • Havre PA, Rice MC, Noe M, Kmiec EB. The human REC2/RAD51B gene acts as a DNA damage sensor by inducing G1 delay and hypersensitivity to ultraviolet irradiation. Cancer Res. 1998 Oct 15;58(20):4733–4739. [PubMed]
  • Havre PA, Rice M, Ramos R, Kmiec EB. HsRec2/Rad51L1, a protein influencing cell cycle progression, has protein kinase activity. Exp Cell Res. 2000 Jan 10;254(1):33–44. [PubMed]
  • Higashijima T, Kataoka A, Nishida T, Yakushiji M. Gonadotropin-releasing hormone agonist therapy induces apoptosis in uterine leiomyoma. Eur J Obstet Gynecol Reprod Biol. 1996 Sep;68(1-2):169–173. [PubMed]
  • Hodges LC, Bergerson JS, Hunter DS, Walker CL. Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Toxicol Sci. 2000 Apr;54(2):355–364. [PubMed]
  • Hofmann GE, Rao CV, Barrows GH, Schultz GS, Sanfilippo JS. Binding sites for epidermal growth factor in human uterine tissues and leiomyomas. J Clin Endocrinol Metab. 1984 May;58(5):880–884. [PubMed]
  • Höppener JW, Mosselman S, Roholl PJ, Lambrechts C, Slebos RJ, de Pagter-Holthuizen P, Lips CJ, Jansz HS, Sussenbach JS. Expression of insulin-like growth factor-I and -II genes in human smooth muscle tumours. EMBO J. 1988 May;7(5):1379–1385. [PMC free article] [PubMed]
  • Houston KD, Hunter DS, Hodges LC, Walker CL. Uterine leiomyomas: mechanisms of tumorigenesis. Toxicol Pathol. 2001 Jan-Feb;29(1):100–104. [PubMed]
  • Hsueh AJ, Peck EJ, Jr, clark JH. Progesterone antagonism of the oestrogen receptor and oestrogen-induced uterine growth. Nature. 1975 Mar 27;254(5498):337–339. [PubMed]
  • Hung TT, Gibbons WE. Evaluation of androgen antagonism of estrogen effect by dihydrotestosterone. J Steroid Biochem. 1983 Oct;19(4):1513–1520. [PubMed]
  • Hunter DS, Hodges LC, Eagon PK, Vonier PM, Fuchs-Young R, Bergerson JS, Walker CL. Influence of exogenous estrogen receptor ligands on uterine leiomyoma: evidence from an in vitro/in vivo animal model for uterine fibroids. Environ Health Perspect. 2000 Oct;108 (Suppl 5):829–834. [PubMed]
  • Hyder SM, Huang JC, Nawaz Z, Boettger-Tong H, Mäkelä S, Chiappetta C, Stancel GM. Regulation of vascular endothelial growth factor expression by estrogens and progestins. Environ Health Perspect. 2000 Oct;108 (Suppl 5):785–790. [PubMed]
  • Hyder SM, Stancel GM, Chiappetta C, Murthy L, Boettger-Tong HL, Makela S. Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen. Cancer Res. 1996 Sep 1;56(17):3954–3960. [PubMed]
  • Ingraham SE, Lynch RA, Kathiresan S, Buckler AJ, Menon AG. hREC2, a RAD51-like gene, is disrupted by t(12;14) (q15;q24.1) in a uterine leiomyoma. Cancer Genet Cytogenet. 1999 Nov;115(1):56–61. [PubMed]
  • Jänne O, Kontula K, Luukkainen T, Vihko R. Oestrogen-induced progesterone receptor in human uterus. J Steroid Biochem. 1975 Mar-Apr;6(3-4):501–509. [PubMed]
  • Jonca F, Ortéga N, Gleizes PE, Bertrand N, Plouët J. Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor. J Biol Chem. 1997 Sep 26;272(39):24203–24209. [PubMed]
  • Kang J, Baxi L, Heller D. Tamoxifen-induced growth of leiomyomas. A case report. J Reprod Med. 1996 Feb;41(2):119–120. [PubMed]
  • Katz VL, Dotters DJ, Droegemeuller W. Complications of uterine leiomyomas in pregnancy. Obstet Gynecol. 1989 Apr;73(4):593–596. [PubMed]
  • Katzenellenbogen BS. Dynamics of steroid hormone receptor action. Annu Rev Physiol. 1980;42:17–35. [PubMed]
  • Kawaguchi K, Fujii S, Konishi I, Iwai T, Nanbu Y, Nonogaki H, Ishikawa Y, Mori T. Immunohistochemical analysis of oestrogen receptors, progesterone receptors and Ki-67 in leiomyoma and myometrium during the menstrual cycle and pregnancy. Virchows Arch A Pathol Anat Histopathol. 1991;419(4):309–315. [PubMed]
  • Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T. Mitotic activity in uterine leiomyomas during the menstrual cycle. Am J Obstet Gynecol. 1989 Mar;160(3):637–641. [PubMed]
  • Kennedy MM, Baigrie CF, Manek S. Tamoxifen and the endometrium: review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology. Int J Gynecol Pathol. 1999 Apr;18(2):130–137. [PubMed]
  • Kiuru M, Launonen V, Hietala M, Aittomäki K, Vierimaa O, Salovaara R, Arola J, Pukkala E, Sistonen P, Herva R, et al. Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology. Am J Pathol. 2001 Sep;159(3):825–829. [PMC free article] [PubMed]
  • Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis. J Reprod Med. 1996 Jul;41(7):483–490. [PubMed]
  • Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925–5930. [PMC free article] [PubMed]
  • Kurbanova M Kh, Koroleva AG, Sergeev AS. Genetiko-épidemiologicheskii analiz miomy matki: otsenka povtornogo riska. Genetika. 1989 Oct;25(10):1896–1898. [PubMed]
  • Lamminen S, Rantala I, Helin H, Rorarius M, Tuimala R. Proliferative activity of human uterine leiomyoma cells as measured by automatic image analysis. Gynecol Obstet Invest. 1992;34(2):111–114. [PubMed]
  • Launonen V, Vierimaa O, Kiuru M, Isola J, Roth S, Pukkala E, Sistonen P, Herva R, Aaltonen LA. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3387–3392. [PMC free article] [PubMed]
  • Le Bouëdec G, de Latour M, Dauplat J. Myomes utérins expansifs sous tamoxifène. 11 observations. Presse Med. 1995 Nov 25;24(36):1694–1696. [PubMed]
  • Leo L, Lanza A, Re A, Tessarolo M, Bellino R, Lauricella A, Wierdis T. Leiomyomas in patients receiving Tamoxifen. Clin Exp Obstet Gynecol. 1994;21(2):94–98. [PubMed]
  • Lessl M, Klotzbuecher M, Schoen S, Reles A, Stöckemann K, Fuhrmann U. Comparative messenger ribonucleic acid analysis of immediate early genes and sex steroid receptors in human leiomyoma and healthy myometrium. J Clin Endocrinol Metab. 1997 Aug;82(8):2596–2600. [PubMed]
  • Levy B, Mukherjee T, Hirschhorn K. Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by comparative genomic hybridization. Cancer Genet Cytogenet. 2000 Aug;121(1):1–8. [PubMed]
  • Liehr JG, Ricci MJ, Jefcoate CR, Hannigan EV, Hokanson JA, Zhu BT. 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: implications for the mechanism of uterine tumorigenesis. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9220–9224. [PMC free article] [PubMed]
  • Ligon AH, Morton CC. Genetics of uterine leiomyomata. Genes Chromosomes Cancer. 2000 Jul;28(3):235–245. [PubMed]
  • Linder D, Gartler SM. Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the study of leiomyomas. Science. 1965 Oct 1;150(3692):67–69. [PubMed]
  • Lindner V, Reidy MA. Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3739–3743. [PMC free article] [PubMed]
  • Longcope C, Johnston CC., Jr Androgen and estrogen dynamics in pre- and postmenopausal women: a comparison between smokers and nonsmokers. J Clin Endocrinol Metab. 1988 Aug;67(2):379–383. [PubMed]
  • Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M, Vudhikamraksa N, Werawatakul Y. Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case--control study. Br J Obstet Gynaecol. 1996 Sep;103(9):909–914. [PubMed]
  • Lumsden MA, West CP, Baird DT. Goserelin therapy before surgery for uterine fibroids. Lancet. 1987 Jan 3;1(8523):36–37. [PubMed]
  • Lumsden MA, West CP, Baird DT. Tamoxifen prolongs luteal phase in premenopausal women but has no effect on the size of uterine fibroids. Clin Endocrinol (Oxf) 1989 Sep;31(3):335–343. [PubMed]
  • Lumsden MA, West CP, Bramley T, Rumgay L, Baird DT. The binding of epidermal growth factor to the human uterus and leiomyomata in women rendered hypo-oestrogenic by continuous administration of an LHRH agonist. Br J Obstet Gynaecol. 1988 Dec;95(12):1299–1304. [PubMed]
  • Lumsden MA, West CP, Hillier H, Baird DT. Estrogenic action of tamoxifen in women treated with luteinizing hormone-releasing hormone agonists (goserelin)--lack of shrinkage of uterine fibroids. Fertil Steril. 1989 Dec;52(6):924–929. [PubMed]
  • Luoto R, Kaprio J, Rutanen EM, Taipale P, Perola M, Koskenvuo M. Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study. Maturitas. 2000 Nov 30;37(1):15–26. [PubMed]
  • Lyons RM, Moses HL. Transforming growth factors and the regulation of cell proliferation. Eur J Biochem. 1990 Feb 14;187(3):467–473. [PubMed]
  • MacMahon B, Trichopoulos D, Cole P, Brown J. Cigarette smoking and urinary estrogens. N Engl J Med. 1982 Oct 21;307(17):1062–1065. [PubMed]
  • Maheux R, Lemay-Turcot L, Lemay A. Daily follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in ten women harboring uterine leiomyomas. Fertil Steril. 1986 Aug;46(2):205–208. [PubMed]
  • Mangrulkar RS, Ono M, Ishikawa M, Takashima S, Klagsbrun M, Nowak RA. Isolation and characterization of heparin-binding growth factors in human leiomyomas and normal myometrium. Biol Reprod. 1995 Sep;53(3):636–646. [PubMed]
  • Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B. Cytogenetical observations in human benign uterine leiomyomas. Anticancer Res. 1988 Jul-Aug;8(4):621–626. [PubMed]
  • Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, Willett WC, Hunter DJ. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997 Dec;90(6):967–973. [PubMed]
  • Marshall LM, Spiegelman D, Goldman MB, Manson JE, Colditz GA, Barbieri RL, Stampfer MJ, Hunter DJ. A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertil Steril. 1998 Sep;70(3):432–439. [PubMed]
  • Marshall LM, Spiegelman D, Manson JE, Goldman MB, Barbieri RL, Stampfer MJ, Willett WC, Hunter DJ. Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking. Epidemiology. 1998 Sep;9(5):511–517. [PubMed]
  • Martucci CP, Fishman J. P450 enzymes of estrogen metabolism. Pharmacol Ther. 1993 Feb-Mar;57(2-3):237–257. [PubMed]
  • Marugo M, Centonze M, Bernasconi D, Fazzuoli L, Berta S, Giordano G. Estrogen and progesterone receptors in uterine leiomyomas. Acta Obstet Gynecol Scand. 1989;68(8):731–735. [PubMed]
  • Maruo T, Matsuo H, Samoto T, Shimomura Y, Kurachi O, Gao Z, Wang Y, Spitz IM, Johansson E. Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids. 2000 Oct-Nov;65(10-11):585–592. [PubMed]
  • Mashal RD, Fejzo ML, Friedman AJ, Mitchner N, Nowak RA, Rein MS, Morton CC, Sklar J. Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata. Genes Chromosomes Cancer. 1994 Sep;11(1):1–6. [PubMed]
  • Maslar IA, Riddick DH. Prolactin production by human endometrium during the normal menstrual cycle. Am J Obstet Gynecol. 1979 Nov 15;135(6):751–754. [PubMed]
  • Massagué J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753–791. [PubMed]
  • McBride G. Benign but no longer forgotten--fibroids get their own conference. Lancet. 1999 Oct 23;354(9188):1450–1450. [PubMed]
  • McCluggage WG, Varma M, Weir P, Bharucha H. Uterine leiomyosarcoma in patient receiving tamoxifen therapy. Acta Obstet Gynecol Scand. 1996 Jul;75(6):593–595. [PubMed]
  • Meadows R. Growing pains. Environ Health Perspect. 1996 Feb;104(2):146–149. [PMC free article] [PubMed]
  • Meloni AM, Surti U, Contento AM, Davare J, Sandberg AA. Uterine leiomyomas: cytogenetic and histologic profile. Obstet Gynecol. 1992 Aug;80(2):209–217. [PubMed]
  • Michnovicz JJ, Hershcopf RJ, Naganuma H, Bradlow HL, Fishman J. Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking. N Engl J Med. 1986 Nov 20;315(21):1305–1309. [PubMed]
  • Miyazono K. Positive and negative regulation of TGF-beta signaling. J Cell Sci. 2000 Apr;113(Pt 7):1101–1109. [PubMed]
  • Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996 Aug 19;392(1):49–53. [PubMed]
  • Murphy AA, Kettel LM, Morales AJ, Roberts VJ, Yen SS. Regression of uterine leiomyomata in response to the antiprogesterone RU 486. J Clin Endocrinol Metab. 1993 Feb;76(2):513–517. [PubMed]
  • Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999 Jan;13(1):9–22. [PubMed]
  • Newbold R. Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens. Environ Health Perspect. 1995 Oct;103 (Suppl 7):83–87. [PMC free article] [PubMed]
  • Newbold RR, DiAugustine RP, Risinger JI, Everitt JI, Walmer DK, Parrott EC, Dixon D. Advances in uterine leiomyoma research: conference overview, summary, and future research recommendations. Environ Health Perspect. 2000 Oct;108 (Suppl 5):769–773. [PubMed]
  • Newbold Retha R, Moore Alicia B, Dixon Darlene. Characterization of uterine leiomyomas in CD-1 mice following developmental exposure to diethylstilbestrol (DES). Toxicol Pathol. 2002 Sep-Oct;30(5):611–616. [PubMed]
  • Nikov GN, Hopkins NE, Boue S, Alworth WL. Interactions of dietary estrogens with human estrogen receptors and the effect on estrogen receptor-estrogen response element complex formation. Environ Health Perspect. 2000 Sep;108(9):867–872. [PMC free article] [PubMed]
  • Nibert M, Heim S. Uterine leiomyoma cytogenetics. Genes Chromosomes Cancer. 1990 May;2(1):3–13. [PubMed]
  • Nisolle M, Gillerot S, Casanas-Roux F, Squifflet J, Berliere M, Donnez J. Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy. Hum Reprod. 1999 Nov;14(11):2844–2850. [PubMed]
  • Nissley P, Lopaczynski W. Insulin-like growth factor receptors. Growth Factors. 1991;5(1):29–43. [PubMed]
  • Nowak RA. Fibroids: pathophysiology and current medical treatment. Baillieres Best Pract Res Clin Obstet Gynaecol. 1999 Jun;13(2):223–238. [PubMed]
  • Nowak RA, Mora S, Diehl T, Rhoades AR, Stewart EA. Prolactin is an autocrine or paracrine growth factor for human myometrial and leiomyoma cells. Gynecol Obstet Invest. 1999;48(2):127–132. [PubMed]
  • Oates AJ, Schumaker LM, Jenkins SB, Pearce AA, DaCosta SA, Arun B, Ellis MJ. The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R), a putative breast tumor suppressor gene. Breast Cancer Res Treat. 1998 Feb;47(3):269–281. [PubMed]
  • Otsuka H, Shinohara M, Kashimura M, Yoshida K, Okamura Y. A comparative study of the estrogen receptor ratio in myometrium and uterine leiomyomas. Int J Gynaecol Obstet. 1989 Jun;29(2):189–194. [PubMed]
  • Otubu JA, Buttram VC, Besch NF, Besch PK. Unconjugated steroids in leiomyomas and tumor-bearing myometrium. Am J Obstet Gynecol. 1982 May 15;143(2):130–133. [PubMed]
  • Ozisik YY, Meloni AM, Powell M, Surti U, Sandberg AA. Chromosome 7 biclonality in uterine leiomyoma. Cancer Genet Cytogenet. 1993 May;67(1):59–64. [PubMed]
  • Ozisik YY, Meloni AM, Surti U, Sandberg AA. Deletion 7q22 in uterine leiomyoma. A cytogenetic review. Cancer Genet Cytogenet. 1993 Nov;71(1):1–6. [PubMed]
  • Packenham JP, du Manoir S, Schrock E, Risinger JI, Dixon D, Denz DN, Evans JA, Berchuck A, Barrett JC, Devereux TR, et al. Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization. Mol Carcinog. 1997 Aug;19(4):273–279. [PubMed]
  • Pandis N, Heim S, Bardi G, Flodérus UM, Willén H, Mandahl N, Mitelman F. Parallel karyotypic evolution and tumor progression in uterine leiomyoma. Genes Chromosomes Cancer. 1990 Nov;2(4):311–317. [PubMed]
  • Parazzini F, La Vecchia C, Negri E, Cecchetti G, Fedele L. Epidemiologic characteristics of women with uterine fibroids: a case-control study. Obstet Gynecol. 1988 Dec;72(6):853–857. [PubMed]
  • Parazzini F, Negri E, La Vecchia C, Chatenoud L, Ricci E, Guarnerio P. Reproductive factors and risk of uterine fibroids. Epidemiology. 1996 Jul;7(4):440–442. [PubMed]
  • Parazzini F, Negri E, La Vecchia C, Fedele L, Rabaiotti M, Luchini L. Oral contraceptive use and risk of uterine fibroids. Obstet Gynecol. 1992 Mar;79(3):430–433. [PubMed]
  • Parazzini F, Negri E, La Vecchia C, Rabaiotti M, Luchini L, Villa A, Fedele L. Uterine myomas and smoking. Results from an Italian study. J Reprod Med. 1996 May;41(5):316–320. [PubMed]
  • Pedeutour F, Quade BJ, Weremowicz S, Dal Cin P, Ali S, Morton CC. Localization and expression of the human estrogen receptor beta gene in uterine leiomyomata. Genes Chromosomes Cancer. 1998 Dec;23(4):361–366. [PubMed]
  • Pledger WJ, Stiles CD, Antoniades HN, Scher CD. An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2839–2843. [PMC free article] [PubMed]
  • Polatti F, Viazzo F, Colleoni R, Nappi RE. Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT. Maturitas. 2000 Nov 30;37(1):27–32. [PubMed]
  • Pollow K, Geilfuss J, Boquoi E, Pollow B. Estrogen and progesterone binding proteins in normal human myometrium and leiomyoma tissue. J Clin Chem Clin Biochem. 1978 Sep;16(9):503–511. [PubMed]
  • Pollow K, Sinnecker G, Boquoi E, Pollow B. In vitro conversion of estradiol-17beta into estrone in normal human myometrium and leiomyoma. J Clin Chem Clin Biochem. 1978 Sep;16(9):493–502. [PubMed]
  • Prentice R, Thompson D, Clifford C, Gorbach S, Goldin B, Byar D. Dietary fat reduction and plasma estradiol concentration in healthy postmenopausal women. The Women's Health Trial Study Group. J Natl Cancer Inst. 1990 Jan 17;82(2):129–134. [PubMed]
  • Presta M. Sex hormones modulate the synthesis of basic fibroblast growth factor in human endometrial adenocarcinoma cells: implications for the neovascularization of normal and neoplastic endometrium. J Cell Physiol. 1988 Dec;137(3):593–597. [PubMed]
  • Pusztai L, Lewis CE, Lorenzen J, McGee JO. Growth factors: regulation of normal and neoplastic growth. J Pathol. 1993 Feb;169(2):191–201. [PubMed]
  • Puukka MJ, Kontula KK, Kauppila AJ, Janne OA, Vihko RK. Estrogen receptor in human myoma tissue. Mol Cell Endocrinol. 1976 Nov;6(1):35–44. [PubMed]
  • Ratech H, Stewart ME. Uterine leiomyomas, serum cholesterol, and oral contraceptives. A preliminary study of epidemiologic differences in Los Angeles, California and Albany, New York. Diagn Gynecol Obstet. 1982 Spring;4(1):21–24. [PubMed]
  • Ratner H. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. Br Med J (Clin Res Ed) 1986 Oct 18;293(6553):1027–1027. [PMC free article] [PubMed]
  • Ravindran J, Kumaraguruparan M. A survey of hysterectomy patterns in Malaysia. Med J Malaysia. 1998 Sep;53(3):263–271. [PubMed]
  • Reed WB, Walker R, Horowitz R. Cutaneous leiomyomata with uterine leiomyomata. Acta Derm Venereol. 1973;53(5):409–416. [PubMed]
  • Reeves R. Structure and function of the HMGI(Y) family of architectural transcription factors. Environ Health Perspect. 2000 Oct;108 (Suppl 5):803–809. [PubMed]
  • Rein MS. Advances in uterine leiomyoma research: the progesterone hypothesis. Environ Health Perspect. 2000 Oct;108 (Suppl 5):791–793. [PubMed]
  • Rein MS, Barbieri RL, Friedman AJ. Progesterone: a critical role in the pathogenesis of uterine myomas. Am J Obstet Gynecol. 1995 Jan;172(1 Pt 1):14–18. [PubMed]
  • Rein MS, Friedman AJ, Heffner LJ. Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist. J Clin Endocrinol Metab. 1990 Jun;70(6):1554–1558. [PubMed]
  • Rein MS, Friedman AJ, Pandian MR, Heffner LJ. The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist. Obstet Gynecol. 1990 Sep;76(3 Pt 1):388–394. [PubMed]
  • Rein MS, Friedman AJ, Stuart JM, MacLaughlin DT. Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate. Fertil Steril. 1990 Jun;53(6):1018–1023. [PubMed]
  • Rein MS, Powell WL, Walters FC, Weremowicz S, Cantor RM, Barbieri RL, Morton CC. Cytogenetic abnormalities in uterine myomas are associated with myoma size. Mol Hum Reprod. 1998 Jan;4(1):83–86. [PubMed]
  • Reynolds LP, Kirsch JD, Kraft KC, Redmer DA. Time-course of the uterine response to estradiol-17beta in ovariectomized ewes: expression of angiogenic factors. Biol Reprod. 1998 Sep;59(3):613–620. [PubMed]
  • Rice MC, Smith ST, Bullrich F, Havre P, Kmiec EB. Isolation of human and mouse genes based on homology to REC2, a recombinational repair gene from the fungus Ustilago maydis. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7417–7422. [PMC free article] [PubMed]
  • Richards PA, Tiltman AJ. Anatomical variation of the oestrogen receptor in the non-neoplastic myometrium of fibromyomatous uteri. Virchows Arch. 1996 Aug;428(6):347–351. [PubMed]
  • Rider V, Carlone DL, Foster RT. Oestrogen and progesterone control basic fibroblast growth factor mRNA in the rat uterus. J Endocrinol. 1997 Jul;154(1):75–84. [PubMed]
  • Robboy SJ, Bentley RC, Butnor K, Anderson MC. Pathology and pathophysiology of uterine smooth-muscle tumors. Environ Health Perspect. 2000 Oct;108 (Suppl 5):779–784. [PubMed]
  • Rosati P, Exacoustòs C, Mancuso S. Longitudinal evaluation of uterine myoma growth during pregnancy. A sonographic study. J Ultrasound Med. 1992 Oct;11(10):511–515. [PubMed]
  • Rose DP, Boyar AP, Cohen C, Strong LE. Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins. J Natl Cancer Inst. 1987 Apr;78(4):623–626. [PubMed]
  • Rose DP, Goldman M, Connolly JM, Strong LE. High-fiber diet reduces serum estrogen concentrations in premenopausal women. Am J Clin Nutr. 1991 Sep;54(3):520–525. [PubMed]
  • Rosenthal SM, Hsiao D, Silverman LA. An insulin-like growth factor-II (IGF-II) analog with highly selective affinity for IGF-II receptors stimulates differentiation, but not IGF-I receptor down-regulation in muscle cells. Endocrinology. 1994 Jul;135(1):38–44. [PubMed]
  • Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. Br Med J (Clin Res Ed) 1986 Aug 9;293(6543):359–362. [PMC free article] [PubMed]
  • Rustin P, Bourgeron T, Parfait B, Chretien D, Munnich A, Rötig A. Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human. Biochim Biophys Acta. 1997 Aug 22;1361(2):185–197. [PubMed]
  • Sabatini R, Di Fazio F, Loizzi P. Uterine leiomyosarcoma in a postmenopausal woman treated with tamoxifen: case report. Eur J Gynaecol Oncol. 1999;20(4):327–328. [PubMed]
  • Sadan O, van Iddekinge B, van Gelderen CJ, Savage N, Becker PJ, van der Walt LA, Robinson M. Oestrogen and progesterone receptor concentrations in leiomyoma and normal myometrium. Ann Clin Biochem. 1987 May;24(Pt 3):263–267. [PubMed]
  • Samadi AR, Lee NC, Flanders WD, Boring JR, 3rd, Parris EB. Risk factors for self-reported uterine fibroids: a case-control study. Am J Public Health. 1996 Jun;86(6):858–862. [PMC free article] [PubMed]
  • Sato F, Miyake H, Nishi M, Kudo R. Fertility and uterine size among Asian women undergoing hysterectomy for leiomyomas. Int J Fertil Womens Med. 2000 Jan-Feb;45(1):34–37. [PubMed]
  • Sato F, Miyake H, Nishi M, Mori M, Kudo R. Early normal menstrual cycle pattern and the development of uterine leiomyomas. J Womens Health Gend Based Med. 2000 Apr;9(3):299–302. [PubMed]
  • Sato F, Nishi M, Kudo R, Miyake H. Body fat distribution and uterine leiomyomas. J Epidemiol. 1998 Aug;8(3):176–180. [PubMed]
  • Sauro MD, Zorn NE. Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C-dependent mechanism. J Cell Physiol. 1991 Jul;148(1):133–138. [PubMed]
  • Saxena SP, Khare C, Farooq A, Murugesan K, Buckshee K, Chandra J. DDT and its metabolites in leiomyomatous and normal human uterine tissue. Arch Toxicol. 1987 Apr;59(6):453–455. [PubMed]
  • Schmidt-Gollwitzer M, Eiletz J, Genz T, Pollow K. Determination of estradiol, estrone, and progesterone in serum and myometrium: correlation with the content of sex steroid receptors and 17 beta-hydroxysteroid dehydrogenase activity throughout the menstrual cycle. J Clin Endocrinol Metab. 1979 Sep;49(3):370–376. [PubMed]
  • Schneider J, Bradlow HL, Strain G, Levin J, Anderson K, Fishman J. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites. J Clin Endocrinol Metab. 1983 May;56(5):973–978. [PubMed]
  • Schoenmakers EF, Huysmans C, Van de Ven WJ. Allelic knockout of novel splice variants of human recombination repair gene RAD51B in t(12;14) uterine leiomyomas. Cancer Res. 1999 Jan 1;59(1):19–23. [PubMed]
  • Schwartz SM, Marshall LM, Baird DD. Epidemiologic contributions to understanding the etiology of uterine leiomyomata. Environ Health Perspect. 2000 Oct;108 (Suppl 5):821–827. [PubMed]
  • Sener AB, Seçkin NC, Ozmen S, Gökmen O, Doğu N, Ekici E. The effects of hormone replacement therapy on uterine fibroids in postmenopausal women. Fertil Steril. 1996 Feb;65(2):354–357. [PubMed]
  • Shaw RW. Mechanism of LHRH analogue action in uterine fibroids. Horm Res. 1989;32 (Suppl 1):150–153. [PubMed]
  • Shikora SA, Niloff JM, Bistrian BR, Forse RA, Blackburn GL. Relationship between obesity and uterine leiomyomata. Nutrition. 1991 Jul-Aug;7(4):251–255. [PubMed]
  • Shinohara A, Ogawa H, Ogawa T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell. 1992 May 1;69(3):457–470. [PubMed]
  • Shu Z, Smith S, Wang L, Rice MC, Kmiec EB. Disruption of muREC2/RAD51L1 in mice results in early embryonic lethality which can Be partially rescued in a p53(-/-) background. Mol Cell Biol. 1999 Dec;19(12):8686–8693. [PMC free article] [PubMed]
  • Silva EG, Tornos CS, Follen-Mitchell M. Malignant neoplasms of the uterine corpus in patients treated for breast carcinoma: the effects of tamoxifen. Int J Gynecol Pathol. 1994 Jul;13(3):248–258. [PubMed]
  • Sonawane BR. Chemical contaminants in human milk: an overview. Environ Health Perspect. 1995 Sep;103 (Suppl 6):197–205. [PMC free article] [PubMed]
  • Soules MR, McCarty KS., Jr Leiomyomas: steroid receptor content. Variation within normal menstrual cycles. Am J Obstet Gynecol. 1982 May 1;143(1):6–11. [PubMed]
  • Spellacy WN, Le Maire WJ, Buhi WC, Birk SA, Bradley BA. Plasma growth hormone and estradiol levels in women with uterine myomas. Obstet Gynecol. 1972 Dec;40(6):829–834. [PubMed]
  • Stellman SD, Djordjevic MV, Muscat JE, Gong L, Bernstein D, Citron ML, White A, Kemeny M, Busch E, Nafziger AN. Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York. Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):489–496. [PubMed]
  • Stewart EA, Nowak RA. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update. 1996 Jul-Aug;2(4):295–306. [PubMed]
  • Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk JJ, Pledger WJ. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279–1283. [PMC free article] [PubMed]
  • Stovall TG, Ling FW, Henry LC, Woodruff MR. A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. Am J Obstet Gynecol. 1991 Jun;164(6 Pt 1):1420–1425. [PubMed]
  • Strawn EY, Jr, Novy MJ, Burry KA, Bethea CL. Insulin-like growth factor I promotes leiomyoma cell growth in vitro. Am J Obstet Gynecol. 1995 Jun;172(6):1837–1844. [PubMed]
  • Strobelt N, Ghidini A, Cavallone M, Pensabene I, Ceruti P, Vergani P. Natural history of uterine leiomyomas in pregnancy. J Ultrasound Med. 1994 May;13(5):399–401. [PubMed]
  • Sumitani H, Shozu M, Segawa T, Murakami K, Yang HJ, Shimada K, Inoue M. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism. Endocrinology. 2000 Oct;141(10):3852–3861. [PubMed]
  • Taioli E, Garte SJ, Trachman J, Garbers S, Sepkovic DW, Osborne MP, Mehl S, Bradlow HL. Ethnic differences in estrogen metabolism in healthy women. J Natl Cancer Inst. 1996 May 1;88(9):617–617. [PubMed]
  • Takahashi T, Eitzman B, Bossert NL, Walmer D, Sparrow K, Flanders KC, McLachlan J, Nelson KG. Transforming growth factors beta 1, beta 2, and beta 3 messenger RNA and protein expression in mouse uterus and vagina during estrogen-induced growth: a comparison to other estrogen-regulated genes. Cell Growth Differ. 1994 Sep;5(9):919–935. [PubMed]
  • Takahashi T, Nagai N, Oda H, Ohama K, Kamada N, Miyagawa K. Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma. Genes Chromosomes Cancer. 2001 Feb;30(2):196–201. [PubMed]
  • Tamaya T, Fujimoto J, Okada H. Comparison of cellular levels of steroid receptors in uterine leiomyoma and myometrium. Acta Obstet Gynecol Scand. 1985;64(4):307–309. [PubMed]
  • Tamaya T, Motoyama T, Ohono Y, Ide N, Tsurusaki T, Okada H. Estradiol-17 beta-, progesterone and 5 alpha-dihydrotestosterone receptors of uterine myometrium and myoma in the human subject. J Steroid Biochem. 1979 Jun;10(6):615–622. [PubMed]
  • Tang XM, Dou Q, Zhao Y, McLean F, Davis J, Chegini N. The expression of transforming growth factor-beta s and TGF-beta receptor mRNA and protein and the effect of TGF-beta s on human myometrial smooth muscle cells in vitro. Mol Hum Reprod. 1997 Mar;3(3):233–240. [PubMed]
  • Taylor AH, Al-Azzawi F. Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol. 2000 Feb;24(1):145–155. [PubMed]
  • Tham DM, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998 Jul;83(7):2223–2235. [PubMed]
  • Thi MT, Baulieu EE, Milgrom E. Comparison of the characteristics and of the hormonal control of endometrial and myometrial progesterone receptors. J Endocrinol. 1975 Sep;66(3):349–356. [PubMed]
  • Thyresson HN, Su WP. Familial cutaneous leiomyomatosis. J Am Acad Dermatol. 1981 Apr;4(4):430–434. [PubMed]
  • Tiltman AJ. The effect of progestins on the mitotic activity of uterine fibromyomas. Int J Gynecol Pathol. 1985;4(2):89–96. [PubMed]
  • TIMONEN S, VAANANEN P. Uterine myoma. Some hormone assays. Acta Endocrinol (Copenh) 1959 Nov;32:384–390. [PubMed]
  • Tomás E, Kauppila A, Blanco G, Apaja-Sarkkinen M, Laatikainen T. Comparison between the effects of tamoxifen and toremifene on the uterus in postmenopausal breast cancer patients. Gynecol Oncol. 1995 Nov;59(2):261–266. [PubMed]
  • Tomlinson Ian P M, Alam N Afrina, Rowan Andrew J, Barclay Ella, Jaeger Emma E M, Kelsell David, Leigh Irene, Gorman Patricia, Lamlum Hanan, Rahman Shamima, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002 Apr;30(4):406–410. [PubMed]
  • Tommola P, Pekonen F, Rutanen EM. Binding of epidermal growth factor and insulin-like growth factor I in human myometrium and leiomyomata. Obstet Gynecol. 1989 Oct;74(4):658–662. [PubMed]
  • Townsend DE, Sparkes RS, Baluda MC, McClelland G. Unicellular histogenesis of uterine leiomyomas as determined by electrophoresis by glucose-6-phosphate dehydrogenase. Am J Obstet Gynecol. 1970 Aug 15;107(8):1168–1173. [PubMed]
  • Treloar SA, Martin NG, Dennerstein L, Raphael B, Heath AC. Pathways to hysterectomy: insights from longitudinal twin research. Am J Obstet Gynecol. 1992 Jul;167(1):82–88. [PubMed]
  • Troiano RP, Flegal KM. Overweight prevalence among youth in the United States: why so many different numbers? Int J Obes Relat Metab Disord. 1999 Mar;23 (Suppl 2):S22–S27. [PubMed]
  • Tseng L, Gurpide E. Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology. 1975 Oct;97(4):825–833. [PubMed]
  • Ugwumadu AH, Harding K. Uterine leiomyomata and endometrial proliferation in postmenopausal women treated with the anti-oestrogen tamoxifen. Eur J Obstet Gynecol Reprod Biol. 1994 Apr;54(2):153–156. [PubMed]
  • Upadhyaya NB, Doody MC, Googe PB. Histopathological changes in leiomyomata treated with leuprolide acetate. Fertil Steril. 1990 Nov;54(5):811–814. [PubMed]
  • van der Heijden O, Chiu HC, Park TC, Takahashi H, LiVolsi VA, Risinger JI, Barrett JC, Berchuck A, Evans AC, Behbakht K, et al. Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q. Mol Carcinog. 1998 Dec;23(4):243–247. [PubMed]
  • Van der Ven LT, Roholl PJ, Gloudemans T, Van Buul-Offers SC, Welters MJ, Bladergroen BA, Faber JA, Sussenbach JS, Den Otter W. Expression of insulin-like growth factors (IGFs), their receptors and IGF binding protein-3 in normal, benign and malignant smooth muscle tissues. Br J Cancer. 1997;75(11):1631–1640. [PMC free article] [PubMed]
  • Van Itallie TB. Health implications of overweight and obesity in the United States. Ann Intern Med. 1985 Dec;103(6 ):983–988. [PubMed]
  • Vanni R, Van Roy N, Lecca U, Speleman F. Uterine leiomyoma cytogenetics. III. Interphase cytogenetic analysis of karyotypically normal uterine leiomyoma excludes possibility of undetected trisomy 12. Cancer Genet Cytogenet. 1992 Aug;62(1):40–42. [PubMed]
  • Velebil P, Wingo PA, Xia Z, Wilcox LS, Peterson HB. Rate of hospitalization for gynecologic disorders among reproductive-age women in the United States. Obstet Gynecol. 1995 Nov;86(5):764–769. [PubMed]
  • Vij U, Murugesan K, Laumas KR, Farooq A. Progestin and antiprogestin interactions with progesterone receptors in human myomas. Int J Gynaecol Obstet. 1990 Apr;31(4):347–353. [PubMed]
  • Vikhlyaeva EM, Khodzhaeva ZS, Fantschenko ND. Familial predisposition to uterine leiomyomas. Int J Gynaecol Obstet. 1995 Nov;51(2):127–131. [PubMed]
  • Viville B, Charnock-Jones DS, Sharkey AM, Wetzka B, Smith SK. Distribution of the A and B forms of the progesterone receptor messenger ribonucleic acid and protein in uterine leiomyomata and adjacent myometrium. Hum Reprod. 1997 Apr;12(4):815–822. [PubMed]
  • Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science. 1985 Feb 8;227(4687):642–645. [PubMed]
  • Vogelstein B, Fearon ER, Hamilton SR, Preisinger AC, Willard HF, Michelson AM, Riggs AD, Orkin SH. Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res. 1987 Sep 15;47(18):4806–4813. [PubMed]
  • Vollenhoven BJ, Herington AC, Healy DL. Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium. J Clin Endocrinol Metab. 1993 May;76(5):1106–1110. [PubMed]
  • Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: a clinical review. Br J Obstet Gynaecol. 1990 Apr;97(4):285–298. [PubMed]
  • Vollenhoven BJ, Pearce P, Herington AC, Healy DL. Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin-releasing hormone agonist pretreated women. Clin Endocrinol (Oxf) 1994 Apr;40(4):537–544. [PubMed]
  • Vu K, Greenspan DL, Wu TC, Zacur HA, Kurman RJ. Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas. Hum Pathol. 1998 Apr;29(4):359–363. [PubMed]
  • Wack JT, Rodin J. Smoking and its effects on body weight and the systems of caloric regulation. Am J Clin Nutr. 1982 Feb;35(2):366–380. [PubMed]
  • Walters CA, Daly DC, Chapitis J, Kuslis ST, Prior JC, Kusmik WF, Riddick DH. Human myometrium: a new potential source of prolactin. Am J Obstet Gynecol. 1983 Nov 15;147(6):639–644. [PubMed]
  • Westhoff C, Gentile G, Lee J, Zacur H, Helbig D. Predictors of ovarian steroid secretion in reproductive-age women. Am J Epidemiol. 1996 Aug 15;144(4):381–388. [PubMed]
  • Wilcox LS, Koonin LM, Pokras R, Strauss LT, Xia Z, Peterson HB. Hysterectomy in the United States, 1988-1990. Obstet Gynecol. 1994 Apr;83(4):549–555. [PubMed]
  • Wilson EA, Yang F, Rees ED. Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissues. Obstet Gynecol. 1980 Jan;55(1):20–24. [PubMed]
  • Woods MN, Barnett JB, Spiegelman D, Trail N, Hertzmark E, Longcope C, Gorbach SL. Hormone levels during dietary changes in premenopausal African-American women. J Natl Cancer Inst. 1996 Oct 2;88(19):1369–1374. [PubMed]
  • Wyshak G, Frisch RE, Albright NL, Albright TE, Schiff I. Lower prevalence of benign diseases of the breast and benign tumours of the reproductive system among former college athletes compared to non-athletes. Br J Cancer. 1986 Nov;54(5):841–845. [PMC free article] [PubMed]
  • Yamamoto T, Takamori K, Okada H. Estrogen biosynthesis in leiomyoma and myometrium of the uterus. Horm Metab Res. 1984 Dec;16(12):678–679. [PubMed]
  • Yeh J, Rein M, Nowak R. Presence of messenger ribonucleic acid for epidermal growth factor (EGF) and EGF receptor demonstrable in monolayer cell cultures of myometria and leiomyomata. Fertil Steril. 1991 Nov;56(5):997–1000. [PubMed]
  • Ylöstalo P, Granberg S, Bäckström AC, Hirsjärvi-Lahti T. Uterine findings by transvaginal sonography during percutaneous estrogen treatment in postmenopausal women. Maturitas. 1996 Apr;23(3):313–317. [PubMed]
  • Yu H, Berkel H. Insulin-like growth factors and cancer. J La State Med Soc. 1999 Apr;151(4):218–223. [PubMed]
  • Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998 Jan;19(1):1–27. [PubMed]
  • Zumoff B, Miller L, Levit CD, Miller EH, Heinz U, Kalin M, Denman H, Jandorek R, Rosenfeld RS. The effect of smoking on serum progesterone, estradiol, and luteinizing hormone levels over a menstrual cycle in normal women. Steroids. 1990 Nov;55(11):507–511. [PubMed]

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