Changes in vaginal morphology, steroid receptor and natural antimicrobial content following treatment with low-dose mifepristone

Contraception

Volumn 75, Issue 4, 2007, Pages 271-280

  Narvekar, Nitish ^a   Lakha, Fatim ^a   Critchley, Hilary O D ^a   Glasier, Anna F ^b   Williams, Alistair R W ^a   Leminen, Riikka ^c   Heikinheimo, Oskari ^c   Kelly, Rodney W ^a   Baird, David T ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b Family Planning and Well Woman Services   (United Kingdom)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Mifepristone; Natural antimicrobial; Pharmacodynamics; Steroid receptors; Vaginal thickness

Indexed keywords

ANDROGEN RECEPTOR; ANTIGESTAGEN; BETA DEFENSIN; BETA DEFENSIN 1; BETA DEFENSIN 2; BETA DEFENSIN 3; BETA DEFENSIN 5; CONTRACEPTIVE AGENT; ELAFIN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; GRANULYSIN; MESSENGER RNA; MIFEPRISTONE; PROGESTERONE; PROGESTERONE RECEPTOR; SECRETORY LEUKOCYTE PROTEINASE INHIBITOR; STEROID RECEPTOR;

ADULT; AMENORRHEA; ANOVULATION; ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIUM CULTURE; BIOPSY; BLOOD CHEMISTRY; BLOOD EXAMINATION; BLOOD PRESSURE; CLINICAL ARTICLE; CONTRACEPTION; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; ECHOGRAPHY; ESTRADIOL BLOOD LEVEL; FEMALE; HEART RATE; HUMAN; HUMAN EXPERIMENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION RISK; LIVER FUNCTION TEST; LOW DRUG DOSE; MORPHOLOGY; NORMAL HUMAN; OPEN STUDY; OVARY FUNCTION; PHARMACODYNAMICS; PILOT STUDY; PROGESTERONE BLOOD LEVEL; SEXUALLY TRANSMITTED DISEASE; SIDE EFFECT; TABLET; TISSUE DISTRIBUTION; TREATMENT DURATION; VAGINA; VAGINA EPITHELIUM; VIRUS TRANSMISSION;

ADULT; ANTI-INFECTIVE AGENTS; ANTIGENS, DIFFERENTIATION, T-LYMPHOCYTE; BETA-DEFENSINS; CONTRACEPTIVES, ORAL, SYNTHETIC; ELAFIN; ENDOMETRIUM; FEMALE; GENE EXPRESSION; HUMANS; MIFEPRISTONE; OVARY; PILOT PROJECTS; RECEPTORS, STEROID; RNA, MESSENGER; SECRETORY LEUKOCYTE PEPTIDASE INHIBITOR; VAGINA;

EID: 33847731867     PISSN: 00107824     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.contraception.2006.11.013     Document Type: Article

References (62)

1. Rehle T., Brinkmann U.K., Siraprapasiri T., Coplan P., Aiemsukawat C., and Ungchusak K. Risk factors of HIV-1 infection among female prostitutes in Khon Kaen, Northeast Thailand. Infection 20 (1992) 328-331
2. Ungchusak K., Rehle T., Thammapornpilap P., Spiegelman D., Brinkmann U., and Siraprapasiri T. Determinants of HIV infection among female commercial sex workers in northeastern Thailand: results from a longitudinal study. J Acquir Immune Defic Syndr Hum Retrovirol 12 (1996) 500-507
3. Nagachinta T., Duerr A., Suriyanon V., et al. Risk factors for HIV-1 transmission from HIV-seropositive male blood donors to their regular female partners in northern Thailand. AIDS 11 (1997) 1765-1772
4. Marx P.A., Spira A.I., Gettie A., Dailey P.J., et al. Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 2 (1996) 1084-1089
5. Morrison C.S., Bright P., Wong E.L., et al. Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections. Sex Transm Dis 31 (2004) 561-567
6. MacLean R. Injectable use may increase women's odds of getting chlamydia or gonorrhea. Int Fam Plan Perspect 31 (2005) 45-46
7. Miller C.J., Alexander N.J., Vogel P., Anderson J., and Marx P.A. Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. J Med Primatol 21 (1992) 64-68
8. Miller C.J. Localization of simian immunodeficiency virus-infected cells in the genital tract of male and female rhesus macaques. J Reprod Immunol 41 (1998) 331-339
9. Mingjia L., and Short R. How estrogen or progesterone might change a woman's susceptibility to HIV-1 infection. Aust N Z J Obstet Gynaecol 42 (2002) 472-475
10. Smith S.M., Baskin G.B., and Marx P.A. Estrogen protects against vaginal transmission of simian immunodeficiency virus. J Infect Dis 182 (2000) 708-715
11. Smith S.M., Mefford M., Sodora D., et al. Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect. AIDS 18 (2004) 1637-1643
12. HIV Study Group. Comparison of female to male and male to female transmission of HIV in 563 stable couples. European Study Group on Heterosexual Transmission of HIV. BMJ 304 (1992) 809-813
13. Aaby P., Ariyoshi K., Buckner M., et al. Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa. AIDS 10 (1996) 1585-1590
14. Klebanoff S.J., and Coombs R.W. Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1: possible role in heterosexual transmission. J Exp Med 174 (1991) 289-292
15. Klebanoff S.J., Hillier S.L., Eschenbach D.A., and Waltersdorph A.M. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis 164 (1991) 94-100
16. Martin H.L., Richardson B.A., Nyange P.M., et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180 (1999) 1863-1868
17. Spira A.I., Marx P.A., Patterson B.K., et al. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 183 (1996) 215-225
18. Hu J., Gardner M.B., and Miller C.J. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 74 (2000) 6087-6095
19. Draper D.L., Landers D.V., Krohn M.A., Hillier S.L., Wiesenfeld H.C., and Heine R.P. Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections. Am J Obstet Gynecol 183 (2000) 1243-1248
20. Pillay K., Coutsoudis A., Agadzi-Naqvi A.K., Kuhn L., Coovadia H.M., and Janoff E.N. Secretory leukocyte protease inhibitor in vaginal fluids and perinatal human immunodeficiency virus type 1 transmission. J Infect Dis 183 (2001) 653-656
21. King A.E., Critchley H.O., Sallenave J.M., and Kelly R.W. Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation. J Clin Endocrinol Metab 88 (2003) 4426-4431
22. Baird D.T. Clinical uses of antiprogestogens. J Soc Gynecol Investig 7 (2000) S49-S52
23. Brown A., Cheng L., Lin S., and Baird D.T. Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days. J Clin Endocrinol Metab 87 (2002) 63-70
24. Baird D.T., Brown A., Cheng L., et al. Mifepristone: a novel estrogen-free daily contraceptive pill. Steroids 68 (2003) 1099-1105
25. Saunders P.T., Millar M.R., Williams K., et al. Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biol Reprod 63 4 (2000) 1098-1105
26. King A.E., Critchley H.O., and Kelly R.W. Presence of secretory leukocyte protease inhibitor in human endometrium and first trimester decidua suggests an antibacterial protective role. Mol Hum Reprod 6 (2000) 191-196
27. King A.E., Fleming D.C., Critchley H.O., and Kelly R.W. Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells. Mol Hum Reprod 8 (2002) 341-349
28. Fleming D.C., King A.E., Williams A.R., Critchley H.O., and Kelly R.W. Hormonal contraception can suppress natural antimicrobial gene transcription in human endometrium. Fertil Steril 79 (2003) 856-863
29. King A.E., Critchley H.O., and Kelly R.W. Innate immune defences in the human endometrium. Reprod Biol Endocrinol 1 (2003) 116
30. King A.E., Fleming D.C., Critchley H.O., and Kelly R.W. Differential expression of the natural antimicrobials, beta-defensins 3 and 4, in human endometrium. J Reprod Immunol 59 (2003) 1-16
31. King A.E., Morgan K., Sallenave J.M., and Kelly R.W. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone. Biochem Biophys Res Commun 310 (2003) 594-599
32. Leminen R., Ranta S., von Hertzen H., Oehler J., and Heikinheimo O. Pharmacokinetics of 10 mg of mifepristone. Contraception 68 (2003) 427-429
33. Heikinheimo O., Tevilin M., Shoupe D., Croxatto H., and Lähteenmäki P. Quantitation of RU486 in human plasma by HPLC and RIA after column chromatography. Contraception 34 (1986) 613-624
34. Sjoberg I., Cajander S., and Rylander E. Morphometric characteristics of the vaginal epithelium during the menstrual cycle. Gynecol Obstet Invest 26 (1988) 136-144
35. Ma Z., Lu F.X., Torten M., and Miller C.J. The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques. Clin Immunol 100 (2001) 240-249
36. Farage M.H., and Maibach H. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet 273 (2006) 195-202
37. Miller L., Patton D.L., Meier A., Thwin S.S., Hooton T.M., and Eschenbach D.A. Depomedroxyprogesterone-induced hypestrogenism and changes in vaginal flora and epithelium. Obstet Gynecol 96 (2000) 431-439
38. Mauck C.K., Callahan M.M., Baker J., et al. The effect of one injection of Depo-Provera on the human vaginal epithelium and cervical ectopy. Contraception 60 (1999) 15-24
39. Bahamondes L., Trevisan M., Andrade L., et al. The effect upon the human vaginal histology of the long-term use of the injectable contraceptive Depo-Provera. Contraception 62 (2000) 23-27
40. Ildgruben A.K., Sjoberg I.M., and Hammarstrom M.L. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol 102 (2003) 571-582
41. Ildgruben A., Sjoberg I., Hammarstrom M.L., and Backstrom T. Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage. Contraception 72 (2005) 383-392
42. Ulfelder H., and Robboy S.J. The embryologic development of the human vagina. Am J Obstet Gynecol 126 (1976) 769-776
43. Grow D.R., Williams R.F., Hsiu J.G., and Hodgen G.D. Antiprogestin and/or gonadotropin-releasing hormone agonist for endometriosis treatment and bone maintenance: a 1-year primate study. J Clin Endocrinol Metab 81 (1996) 1933-1939
44. MacLean A.B., Nicol L.A., and Hodgins M.B. Immunohistochemical localization of estrogen receptors in the vulva and vagina. J Reprod Med 35 (1990) 1015-1016
45. Hodgins M.B., Spike R.C., Mackie R.M., and MacLean A.B. An immunohistochemical study of androgen, estrogen and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol 105 (1998) 216-222
46. Blakeman P.J., Hilton P., and Bulmer J.N. Estrogen and progesterone receptor expression in the female lower urinary tract, with reference to estrogen status. BJU Int 86 (2000) 32-38
47. Pelletier G., and El-Alfy M. Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab 85 (2000) 4835-4840
48. Gebhart J.B., Rickard D.J., Barrett T.J., et al. Expression of estrogen receptor isoforms alpha and beta messenger RNA in vaginal tissue of premenopausal and postmenopausal women. Am J Obstet Gynecol 185 (2001) 1325-1330 [discussion 1330-31]
49. Traish A.M., Kim N., Min K., Munarriz R., and Goldstein I. Role of androgens in female genital sexual arousal: receptor expression, structure, and function. Fertil Steril 77 Suppl 4 (2002) S11-S18
50. Berman J.R., Almeida F.G., Jolin J., Raz S., Chaudhuri G., and Gonzalez-Cadavid N.F. Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril 79 (2003) 925-931
51. Fu X., Rezapour M., Wu X., Li L., Sjogren C., and Ulmsten U. Expression of estrogen receptor-alpha and -beta in anterior vaginal walls of genuine stress incontinent women. Int Urogynecol J Pelvic Floor Dysfunct 14 (2003) 276-281 [discussion 281]
52. Brenner R.M., Slayden O.D., Nayak N.R., Baird D.T., and Critchley H.O. A role for the androgen receptor in the endometrial antiproliferative effects of progesterone antagonists. Steroids 68 (2003) 1033-1039
53. Slayden O.D., and Brenner R.M. Flutamide counteracts the antiproliferative effects of antiprogestins in the primate endometrium. J Clin Endocrinol Metab 88 (2003) 946-949
54. Narvekar N., Cameron S., Critchley H.O., Lin S., Cheng L., and Baird D.T. Low-dose mifepristone inhibits endometrial proliferation and up-regulates androgen receptor. J Clin Endocrinol Metab 89 (2004) 2491-2497
55. Baird D.T., Brown A., Critchley H.O., Williams A.R., Lin S., and Cheng L. Effect of long-term treatment with low-dose mifepristone on the endometrium. Hum Reprod 18 (2003) 61-68
56. McNeely T.B., Dealy M., Dripps D.J., Orenstein J.M., Eisenberg S.P., and Wahl S.M. Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. J Clin Invest 96 (1995) 456-464
57. Farquhar C., VanCott T.C., Mbori-Ngacha D.A., et al. Salivary secretory leukocyte protease inhibitor is associated with reduced transmission of human immunodeficiency virus type 1 through breast milk. J Infect Dis 186 (2002) 1173-1176
58. Valore E.V., Park C.H., Quayle A.J., Wiles K.R., McCray Jr. P.B., and Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101 (1998) 1633-1642
59. Pfundt R., van Ruissen F., van Vlijmen-Willems I.M., et al. Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia. J Clin Invest 98 (1996) 1389-1399
60. Cameron S.T., Thong K.J., and Baird D.T. Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth. Clin Endocrinol (Oxf) 43 (1995) 407-414
61. Kekkonen R., Heikinheimo O., Mandelin E., and Lahteenmaki P. Pharmacokinetics of mifepristone after low oral doses. Contraception 54 (1996) 229-234
62. Narvekar N., Critchley H.O.D., Cheng L., and Baird D.T. Mifepristone induced amenorrhea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal VEGF. Hum Reprod 21 9 (2006) 2312-2318