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DOI: 10.1055/s-0031-1287664
Molecular and Cellular Causes of Abnormal Uterine Bleeding of Endometrial Origin
Publication History
Publication Date:
07 November 2011 (online)

ABSTRACT
Women today may reasonably anticipate in the order of some 400 menstrual cycles over their reproductive lifespan. The endometrium is thus subject to repeat cycles of shedding and repair and notably healing of the endometrium post menses is “scarless”. The local molecular and cellular mechanisms involved in post menstrual resolution of the inflammatory events associated with menstruation and endometrial repair remain to be fully determined. Menstrual complaints are common. It is highly likely that unrestrained local inflammatory events and/ or deficient repair processes within the endometrium contribute to the women's experience of heavy menstrual bleeding (HMB). The management of women with HMB may need to utilize therapeutic approaches that optimize endometrial repair processes, post menses. These approaches may be necessary in addition to current therapies that hitherto have focused on limiting the local inflammation associated with menstruation. Research endeavors thus need to focus upon the molecular and cellular causes of problematic uterine bleeding. Herein the events associated with pre-menstrual progesterone withdrawal, limitation of blood loss, the expression of vasoactive mediators and factors that may modulate vascular morphology are described. Such lines of enquiry and knowledge will be essential if novel targets for treatment of menstrual bleeding complaints, such as HMB, are to be identified.
KEYWORDS
Abnormal uterine bleeding - heavy menstrual bleeding - endometrium - mechanisms
REFERENCES
- 1
Treloar AE, Boynton RE, Behn BG, Brown BW.
Variation of the human menstrual cycle through reproductive life.
Int J Fertil.
1967;
12
(1 Pt 2)
77-126
MissingFormLabel
- 2
Maybin J, Critchley H.
Repair and regeneration of the human endometrium.
Expert Rev Obstet Gynecol.
2009;
4
283-298
MissingFormLabel
- 3
Finn CA, Pope M.
Control of leucocyte infiltration into the decidualized mouse uterus.
J Endocrinol.
1986;
110
(1)
93-96
MissingFormLabel
- 4
Salamonsen LA.
Tissue injury and repair in the female human reproductive tract.
Reproduction.
2003;
125
(3)
301-311
MissingFormLabel
- 5
King AE, Critchley HO.
Oestrogen and progesterone regulation of inflammatory processes in the human endometrium.
J Steroid Biochem Mol Biol.
2010;
120
(2–3)
116-126
MissingFormLabel
- 6 Maybin J. Secrets of the womb. The Max Perutz Prize 2009. Available at: http://wwwguardiancouk/education/2009/aug/31/max-perutz-science-writing-prize
MissingFormLabel
- 7 National Institute for Health and Clinical Excellence .Clinical Guideline 44; Heavy menstrual bleeding. Available at: http://www.nice.org.uk/nicemedia/pdf/CG44FullGuideline.pdf Accessed May 20, 2011
MissingFormLabel
- 8
Lethaby A, Hickey M, Garry R, Penninx J.
Endometrial resection/ablation techniques for heavy menstrual bleeding.
Cochrane Database Syst Rev.
2009;
(4)
CD001501
MissingFormLabel
- 9
Coulter A, Peto V, Doll H.
Patients' preferences and general practitioners' decisions in the treatment of menstrual
disorders.
Fam Pract.
1994;
11
(1)
67-74
MissingFormLabel
- 10
Cromwell DA, Mahmood TA, Templeton A, van der Meulen JH.
Surgery for menorrhagia within English regions: variation in rates of endometrial
ablation and hysterectomy.
BJOG.
2009;
116
(10)
1373-1379
MissingFormLabel
- 11
Guttinger A, Critchley HO.
Endometrial effects of intrauterine levonorgestrel.
Contraception.
2007;
75
(6, Suppl)
S93-S98
MissingFormLabel
- 12
McLennan CE, Rydell AH.
Extent of endometrial shedding during normal menstruation.
Obstet Gynecol.
1965;
26
(5)
605-621
MissingFormLabel
- 13
Gaide Chevronnay HP, Galant C, Lemoine P, Courtoy PJ, Marbaix E, Henriet P.
Spatiotemporal coupling of focal extracellular matrix degradation and reconstruction
in the menstrual human endometrium.
Endocrinology.
2009;
150
(11)
5094-5105
MissingFormLabel
- 14
Critchley HO, Kelly RW, Brenner RM, Baird DT.
The endocrinology of menstruation—a role for the immune system.
Clin Endocrinol (Oxf).
2001;
55
(6)
701-710
MissingFormLabel
- 15
Critchley HO, Kelly RW, Baird DT, Brenner RM.
Regulation of human endometrial function: mechanisms relevant to uterine bleeding.
Reprod Biol Endocrinol.
2006;
4
(Suppl 1)
S5
MissingFormLabel
- 16
Ponnampalam AP, Weston GC, Trajstman AC, Susil B, Rogers PA.
Molecular classification of human endometrial cycle stages by transcriptional profiling.
Mol Hum Reprod.
2004;
10
(12)
879-893
MissingFormLabel
- 17
Critchley HO, Robertson KA, Forster T, Henderson TA, Williams AR, Ghazal P.
Gene expression profiling of mid to late secretory phase endometrial biopsies from
women with menstrual complaint.
Am J Obstet Gynecol.
2006;
195
(2)
406
e1-e16
MissingFormLabel
- 18
Talbi S, Hamilton AE, Vo KC et al..
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and
underlying biological processes in normo-ovulatory women.
Endocrinology.
2006;
147
(3)
1097-1121
MissingFormLabel
- 19
Fan X, Krieg S, Kuo CJ et al..
VEGF blockade inhibits angiogenesis and reepithelialization of endometrium.
FASEB J.
2008;
22
(10)
3571-3580
MissingFormLabel
- 20
Galant C, Berlière M, Dubois D et al..
Focal expression and final activity of matrix metalloproteinases may explain irregular
dysfunctional endometrial bleeding.
Am J Pathol.
2004;
165
(1)
83-94
MissingFormLabel
- 21
Marbaix E, Kokorine I, Moulin P, Donnez J, Eeckhout Y, Courtoy PJ.
Menstrual breakdown of human endometrium can be mimicked in vitro and is selectively
and reversibly blocked by inhibitors of matrix metalloproteinases.
Proc Natl Acad Sci U S A.
1996;
93
(17)
9120-9125
MissingFormLabel
- 22
Critchley HO, Jones RL, Lea RG et al..
Role of inflammatory mediators in human endometrium during progesterone withdrawal
and early pregnancy.
J Clin Endocrinol Metab.
1999;
84
(1)
240-248
MissingFormLabel
- 23
Hannan NJ, Jones RL, Critchley HO et al..
Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium
from users of progestin-only contraception supports a role for fractalkine in leukocyte
recruitment and endometrial remodeling.
J Clin Endocrinol Metab.
2004;
89
(12)
6119-6129
MissingFormLabel
- 24
Hapangama DK, Critchley HO, Henderson TA, Baird DT.
Mifepristone-induced vaginal bleeding is associated with increased immunostaining
for cyclooxygenase-2 and decrease in prostaglandin dehydrogenase in luteal phase endometrium.
J Clin Endocrinol Metab.
2002;
87
(11)
5229-5234
MissingFormLabel
- 25
Milne SA, Jabbour HN.
Prostaglandin (PG) F(2alpha) receptor expression and signaling in human endometrium:
role of PGF(2alpha) in epithelial cell proliferation.
J Clin Endocrinol Metab.
2003;
88
(4)
1825-1832
MissingFormLabel
- 26
Milne SA, Perchick GB, Boddy SC, Jabbour HN.
Expression, localization, and signaling of PGE(2) and EP2/EP4 receptors in human nonpregnant
endometrium across the menstrual cycle.
J Clin Endocrinol Metab.
2001;
86
(9)
4453-4459
MissingFormLabel
- 27
Sales KJ, List T, Boddy SC et al..
A novel angiogenic role for prostaglandin F2alpha-FP receptor interaction in human
endometrial adenocarcinomas.
Cancer Res.
2005;
65
(17)
7707-7716
MissingFormLabel
- 28
Sales KJ, Maldonado-Pérez D, Grant V et al..
Prostaglandin F(2alpha)-F-prostanoid receptor regulates CXCL8 expression in endometrial
adenocarcinoma cells via the calcium-calcineurin-NFAT pathway.
Biochim Biophys Acta.
2009;
1793
(12)
1917-1928
MissingFormLabel
- 29
Keightley MC, Brown P, Jabbour HN, Sales KJ.
F-Prostaglandin receptor regulates endothelial cell function via fibroblast growth
factor-2.
BMC Cell Biol.
2010;
11
8
MissingFormLabel
- 30
Bonatz G, Hansmann ML, Buchholz F, Mettler L, Radzun HJ, Semm K.
Macrophage- and lymphocyte-subtypes in the endometrium during different phases of
the ovarian cycle.
Int J Gynaecol Obstet.
1992;
37
(1)
29-36
MissingFormLabel
- 31
Jones RL, Hannan NJ, Kaitu'u TJ, Zhang J, Salamonsen LA.
Identification of chemokines important for leukocyte recruitment to the human endometrium
at the times of embryo implantation and menstruation.
J Clin Endocrinol Metab.
2004;
89
(12)
6155-6167
MissingFormLabel
- 32
Critchley HO, Kelly RW, Brenner RM, Baird DT.
Antiprogestins as a model for progesterone withdrawal.
Steroids.
2003;
68
(10–13)
1061-1068
MissingFormLabel
- 33
Salamonsen LA, Woolley DE.
Menstruation: induction by matrix metalloproteinases and inflammatory cells.
J Reprod Immunol.
1999;
44
(1–2)
1-27
MissingFormLabel
- 34
Salamonsen LA, Lathbury LJ.
Endometrial leukocytes and menstruation.
Hum Reprod Update.
2000;
6
(1)
16-27
MissingFormLabel
- 35
Le Y, Zhou Y, Iribarren P, Wang J.
Chemokines and chemokine receptors: their manifold roles in homeostasis and disease.
Cell Mol Immunol.
2004;
1
(2)
95-104
MissingFormLabel
- 36
Kaitu'u-Lino TJ, Morison NB, Salamonsen LA.
Neutrophil depletion retards endometrial repair in a mouse model.
Cell Tissue Res.
2007;
328
(1)
197-206
MissingFormLabel
- 37
Wynn TA.
Cellular and molecular mechanisms of fibrosis.
J Pathol.
2008;
214
(2)
199-210
MissingFormLabel
- 38
Eidukaite A, Tamosiunas V.
Endometrial and peritoneal macrophages: expression of activation and adhesion molecules.
Am J Reprod Immunol.
2004;
52
(2)
113-117
MissingFormLabel
- 39
Markee JE.
Menstruation in intraocular transplants in the rhesus monkey.
Contrib Embryol Carnegie Inst.
1940;
28
219-308
MissingFormLabel
- 40
Smith SK.
Regulation of angiogenesis in the endometrium.
Trends Endocrinol Metab.
2001;
12
(4)
147-151
MissingFormLabel
- 41
Abel MH, Zhu C, Baird DT.
An animal model to study menstrual bleeding.
Res Clin Forums.
1982;
4
25-34
MissingFormLabel
- 42
Pickles VR.
A plain-muscle stimulant in the menstruum.
Nature.
1957;
180
(4596)
1198-1199
MissingFormLabel
- 43
O'Reilly G, Charnock-Jones DS, Davenport AP, Cameron IT, Smith SK.
Presence of messenger ribonucleic acid for endothelin-1, endothelin-2, and endothelin-3
in human endometrium and a change in the ratio of ETA and ETB receptor subtype across
the menstrual cycle.
J Clin Endocrinol Metab.
1992;
75
(6)
1545-1549
MissingFormLabel
- 44
Ahmed A, Li XF, Shams M et al..
Localization of the angiotensin II and its receptor subtype expression in human endometrium
and identification of a novel high-affinity angiotensin II binding site.
J Clin Invest.
1995;
96
(2)
848-857
MissingFormLabel
- 45
Hellebrekers BW, Trimbos-Kemper TC, Trimbos JB, Emeis JJ, Kooistra T.
Use of fibrinolytic agents in the prevention of postoperative adhesion formation.
Fertil Steril.
2000;
74
(2)
203-212
MissingFormLabel
- 46
Gleeson N, Devitt M, Sheppard BL, Bonnar J.
Endometrial fibrinolytic enzymes in women with normal menstruation and dysfunctional
uterine bleeding.
Br J Obstet Gynaecol.
1993;
100
(8)
768-771
MissingFormLabel
- 47
Nordengren J, Pilka R, Noskova V et al..
Differential localization and expression of urokinase plasminogen activator (uPA),
its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in endometrial tissue
during the menstrual cycle.
Mol Hum Reprod.
2004;
10
(9)
655-663
MissingFormLabel
- 48
Christiaens GC, Sixma JJ, Haspels AA.
Morphology of haemostasis in menstrual endometrium.
Br J Obstet Gynaecol.
1980;
87
(5)
425-439
MissingFormLabel
- 49
Gleeson NC, Buggy F, Sheppard BL, Bonnar J.
The effect of tranexamic acid on measured menstrual loss and endometrial fibrinolytic
enzymes in dysfunctional uterine bleeding.
Acta Obstet Gynecol Scand.
1994;
73
(3)
274-277
MissingFormLabel
- 50
Preston JT, Cameron IT, Adams EJ, Smith SK.
Comparative study of tranexamic acid and norethisterone in the treatment of ovulatory
menorrhagia.
Br J Obstet Gynaecol.
1995;
102
(5)
401-406
MissingFormLabel
- 51
Ludwig H, Spornitz UM.
Microarchitecture of the human endometrium by scanning electron microscopy: menstrual
desquamation and remodeling.
Ann N Y Acad Sci.
1991;
622
28-46
MissingFormLabel
- 52
Cao W, Mah K, Carroll RS, Slayden OD, Brenner RM.
Progesterone withdrawal up-regulates fibronectin and integrins during menstruation
and repair in the rhesus macaque endometrium.
Hum Reprod.
2007;
22
(12)
3223-3231
MissingFormLabel
- 53
Tresserra F, Grases P, Ubeda A, Pascual MA, Grases PJ, Labastida R.
Morphological changes in hysterectomies after endometrial ablation.
Hum Reprod.
1999;
14
(6)
1473-1477
MissingFormLabel
- 54
Wood C, Rogers P.
A pregnancy after planned partial endometrial resection.
Aust N Z J Obstet Gynaecol.
1993;
33
(3)
316-318
MissingFormLabel
- 55
Ferenczy A, Bertrand G, Gelfand MM.
Proliferation kinetics of human endometrium during the normal menstrual cycle.
Am J Obstet Gynecol.
1979;
133
(8)
859-867
MissingFormLabel
- 56
Padykula HA, Coles LG, Okulicz WC et al..
The basalis of the primate endometrium: a bifunctional germinal compartment.
Biol Reprod.
1989;
40
(3)
681-690
MissingFormLabel
- 57
Gargett CE, Masuda H.
Adult stem cells in the endometrium.
Mol Hum Reprod.
2010;
16
(11)
818-834
MissingFormLabel
- 58
Lumsden MA, Kelly RW, Baird DT.
Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2 alpha.
Br J Obstet Gynaecol.
1983;
90
(12)
1135-1140
MissingFormLabel
- 59
Smith SK, Abel MH, Kelly RW, Baird DT.
Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine
bleeding.
Br J Obstet Gynaecol.
1981;
88
(4)
434-442
MissingFormLabel
- 60
Willman EA, Collins WP, Clayton SG.
Studies in the involvement of prostaglandins in uterine symptomatology and pathology.
Br J Obstet Gynaecol.
1976;
83
(5)
337-341
MissingFormLabel
- 61
Baird DT, Cameron ST, Critchley HO et al..
Prostaglandins and menstruation.
Eur J Obstet Gynecol Reprod Biol.
1996;
70
(1)
15-17
MissingFormLabel
- 62
Smith OP, Jabbour HN, Critchley HO.
Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are
enhanced in heavy menstruation.
Hum Reprod.
2007;
22
(5)
1450-1456
MissingFormLabel
- 63
Smith SK, Abel MH, Kelly RW, Baird DT.
A role for prostacyclin (PGi2) in excessive menstrual bleeding.
Lancet.
1981;
1
(8219)
522-524
MissingFormLabel
- 64
Battersby S, Critchley HO, de Brum-Fernandes AJ, Jabbour HN.
Temporal expression and signalling of prostacyclin receptor in the human endometrium
across the menstrual cycle.
Reproduction.
2004;
127
(1)
79-86
MissingFormLabel
- 65
Murata T, Ushikubi F, Matsuoka T et al..
Altered pain perception and inflammatory response in mice lacking prostacyclin receptor.
Nature.
1997;
388
(6643)
678-682
MissingFormLabel
- 66
Ueno A, Naraba H, Ikeda Y et al..
Intrinsic prostacyclin contributes to exudation induced by bradykinin or carrageenin:
a study on the paw edema induced in IP-receptor-deficient mice.
Life Sci.
2000;
66
(12)
PL155-PL160
MissingFormLabel
- 67
Smith OP, Battersby S, Sales KJ, Critchley HO, Jabbour HN.
Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium
via cross talk with epidermal growth factor receptor and the extracellular signaling
receptor kinase 1/2 pathway.
Endocrinology.
2006;
147
(4)
1697-1705
MissingFormLabel
- 68
Marsh MM, Malakooti N, Taylor NH, Findlay JK, Salamonsen LA.
Endothelin and neutral endopeptidase in the endometrium of women with menorrhagia.
Hum Reprod.
1997;
12
(9)
2036-2040
MissingFormLabel
- 69
Hurskainen R, Teperi J, Paavonen J, Cacciatore B.
Menorrhagia and uterine artery blood flow.
Hum Reprod.
1999;
14
(1)
186-189
MissingFormLabel
- 70
Mints M, Hultenby K, Zetterberg E et al..
Wall discontinuities and increased expression of vascular endothelial growth factor-A
and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels
of women with menorrhagia.
Fertil Steril.
2007;
88
(3)
691-697
MissingFormLabel
- 71
Girling JE, Rogers PA.
Regulation of endometrial vascular remodelling: role of the vascular endothelial growth
factor family and the angiopoietin-TIE signalling system.
Reproduction.
2009;
138
(6)
883-893
MissingFormLabel
- 72
Abberton KM, Healy DL, Rogers PA.
Smooth muscle alpha actin and myosin heavy chain expression in the vascular smooth
muscle cells surrounding human endometrial arterioles.
Hum Reprod.
1999;
14
(12)
3095-3100
MissingFormLabel
- 73
Kooy J, Taylor NH, Healy DL, Rogers PA.
Endothelial cell proliferation in the endometrium of women with menorrhagia and in
women following endometrial ablation.
Hum Reprod.
1996;
11
(5)
1067-1072
MissingFormLabel
- 74
Hewett P, Nijjar S, Shams M, Morgan S, Gupta J, Ahmed A.
Down-regulation of angiopoietin-1 expression in menorrhagia.
Am J Pathol.
2002;
160
(3)
773-780
MissingFormLabel
- 75
Malik S, Day K, Perrault I, Charnock-Jones DS, Smith SK.
Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in menstrual
endometrium and effluent in women with menorrhagia.
Hum Reprod.
2006;
21
(8)
2158-2166
MissingFormLabel
- 76
Arkonac BM, Foster LC, Sibinga NE et al..
Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like
growth factor in vascular endothelial cells.
J Biol Chem.
1998;
273
(8)
4400-4405
MissingFormLabel
- 77
Blum S, Issbrüker K, Willuweit A et al..
An inhibitory role of the phosphatidylinositol 3-kinase-signaling pathway in vascular
endothelial growth factor-induced tissue factor expression.
J Biol Chem.
2001;
276
(36)
33428-33434
MissingFormLabel
- 78 Cullen W. Of the menorrhagia, or the immoderate flow of the menses. In: First Lines of the Practice of Physic. Vol 3, Part 1, Book IV. Edinburgh, Scotland: Bell & Bradfute; 1796
MissingFormLabel
- 79 Huang KC. The Pharmacology of Chinese Herbs. London, UK; Tokyo, Japan: CRC Press; 1993: 275-278
MissingFormLabel
- 80
Small GR, Hadoke PW, Sharif I et al..
Preventing local regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase
type 1 enhances angiogenesis.
Proc Natl Acad Sci U S A.
2005;
102
(34)
12165-12170
MissingFormLabel
- 81
McDonald SE, Henderson TA, Gomez-Sanchez CE, Critchley HO, Mason JI.
11Beta-hydroxysteroid dehydrogenases in human endometrium.
Mol Cell Endocrinol.
2006;
248
(1-2)
72-78
MissingFormLabel
- 82
Rae M, Mohamad A, Price D et al..
Cortisol inactivation by 11beta-hydroxysteroid dehydrogenase-2 may enhance endometrial
angiogenesis via reduced thrombospondin-1 in heavy menstruation.
J Clin Endocrinol Metab.
2009;
94
(4)
1443-1450
MissingFormLabel
- 83
Lee T, Nesselroth SM, Olson ET et al..
Thrombospondin-1-induced vascular smooth muscle cell chemotaxis: the role of the type
3 repeat and carboxyl terminal domains.
J Cell Biochem.
2003;
89
(3)
500-506
MissingFormLabel
- 84
Girling JE, Rogers PA.
Recent advances in endometrial angiogenesis research.
Angiogenesis.
2005;
8
(2)
89-99
MissingFormLabel
- 85 Munro MG. Abnormal Uterine Bleeding. Cambridge, UK: Cambridge University Press; 2010
MissingFormLabel
- 86
Lacey Jr JV, Chia VM.
Endometrial hyperplasia and the risk of progression to carcinoma.
Maturitas.
2009;
63
(1)
39-44
MissingFormLabel
- 87 Hamou JE. Hysteroscopy and Microcolpohysteroscopy. Norwalk, CT: Appleton and Lange; 1992
MissingFormLabel
- 88
Livingstone M, Fraser IS.
Mechanisms of abnormal uterine bleeding.
Hum Reprod Update.
2002;
8
(1)
60-67
MissingFormLabel
- 89
Fraser IS, Baird DT.
Endometrial cystic glandular hyperplasia in adolescent girls.
J Obstet Gynaecol Br Commonw.
1972;
79
(11)
1009-1015
MissingFormLabel
- 90
Fraser IS, Michie EA, Wide L, Baird DT.
Pituitary gonadotropins and ovarian function in adolescent dysfunctional uterine bleeding.
J Clin Endocrinol Metab.
1973;
37
(3)
407-414
MissingFormLabel
- 91
Van Look PF, Hunter WM, Fraser IS, Baird DT.
Impaired estrogen-induced luteinizing hormone release in young women with anovulatory
dysfunctional uterine bleeding.
J Clin Endocrinol Metab.
1978;
46
(5)
816-823
MissingFormLabel
- 92
Hart R, Hickey M, Franks S.
Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome.
Best Pract Res Clin Obstet Gynaecol.
2004;
18
(5)
671-683
MissingFormLabel
- 93
Claessens EA, Cowell CA.
Acute adolescent menorrhagia.
Am J Obstet Gynecol.
1981;
139
(3)
277-280
MissingFormLabel
- 94
Hale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS.
Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase
(LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition.
Menopause.
2009;
16
(1)
50-59
MissingFormLabel
- 95
Baerwald AR, Adams GP, Pierson RA.
A new model for ovarian follicular development during the human menstrual cycle.
Fertil Steril.
2003;
80
(1)
116-122
MissingFormLabel
- 96
Hale GE, Manconi F, Luscombe G, Fraser IS.
Quantitative measurements of menstrual blood loss in ovulatory and anovulatory cycles
in middle- and late-reproductive age and the menopausal transition.
Obstet Gynecol.
2010;
115
(2 Pt 1)
249-256
MissingFormLabel
- 97
Brown JB, Kellar R, Matthew GD.
Preliminary observations on urinary oestrogen excretion in certain gynaecological
disorders.
J Obstet Gynaecol Br Emp.
1959;
66
(2)
177-211
MissingFormLabel
- 98
Fraser IS, Baird DT.
Blood production and ovarian secretion rates of estradiol-17 beta and estrone in women
with dysfunctional uterine bleeding.
J Clin Endocrinol Metab.
1974;
39
(3)
564-570
MissingFormLabel
Hilary O.D. CritchleyM.D.
MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical
Research Institute
47 Little France Crescent, Edinburgh, Midlothian EH16 4TJ, UK
Email: hilary.critchley@ed.ac.uk