Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant

Zhao, Shumei; Choksuchat, Chainarong; Zhao, Yueqin; Ballagh, Susan A.; Kovalevsky, G.; Archer, David F.

doi:10.1016/j.contraception.2008.12.010

Cited by 12 publications

(12 citation statements)

References 53 publications

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“…In the current study we sought to describe the effect of COCs on MMP-2 and -9 as well as the effect of doxycycline on these same MMPs in women taking a COC.MMP-9 is present in the endometrium throughout the menstrual cycle with levels highest in the mid to late luteal and peri-menstrual phases [5, 7, 14]. MMP-2 is predominantly expressed in endometrial stromal cells [5, 7].…”

Section: Discussionmentioning

confidence: 99%

“…MMP-2 is predominantly expressed in endometrial stromal cells [5, 7]. Similar to MMP-9, expression of MMP-2 is high during the menstrual phase [5].…”

Section: Discussionmentioning

confidence: 99%

“…MMP-2 is predominantly expressed in endometrial stromal cells [5, 7]. Similar to MMP-9, expression of MMP-2 is high during the menstrual phase [5]. As gelatinases, MMP-2 and -9 degrade the extracellular matrix and major components of the subendothelial basement membrane which increases vessel fragility [15].…”

Section: Discussionmentioning

confidence: 99%

“…Recent investigations aimed at decreasing unscheduled bleeding with hormonal contraceptives have focused on preventing endometrial degradation on a molecular level by altering matrix metalloproteinases (MMPs)[2–5]. MMPs are present throughout the endometrium with higher MMP activity associated with greater endometrial degradation and subsequent bleeding[6, 7].…”

Section: Introductionmentioning

confidence: 99%

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Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity

et al. 2016

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Objectives To describe the effect of combined oral contraceptives (COC) on Matrix Metalloproteinase (MMP) -2 and -9 activity and compare MMP activity in women taking aCOC with or without doxycycline. Study Design Subjects (n=20) underwent endometrial biopsies1) in the late luteal phase of a baseline cycle prior to initiating COCs, 2) on day 19 to 21 while taking COCs in a standard 28-day cycle (7-day hormone free interval), 3) on day 26 to 28 while taking active COCs continuously for a 28 day cycle. During the continuous COC cycle, they were randomized to receive daily sub-antimicrobial dose doxycycline 40 mg or placebo. Results Compared to baseline, COC treatment increased MMP-2 (p<0.001) and -9(p<0.001). MMP activity was lower in subjects taking a COC with doxycycline compared to those receiving placebo, although only significantly lower for MMP-2LF (p=0.002). Conclusions Unscheduled bleeding with COCs may be the result of increased endometrial MMPs. Sample size limitations prevent us from determining how doxycycline affects MMP activity in COC-users.

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Section: Discussionmentioning

confidence: 99%

“…MMP-2 is predominantly expressed in endometrial stromal cells [5, 7]. Similar to MMP-9, expression of MMP-2 is high during the menstrual phase [5].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity

et al. 2016

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“…Endometrial MMPs are increased during the use of progestin-only contraceptive methods and have been implicated in the associated irregular bleeding. 51 Endometrial MMPs 1, 3, 9, and 14 are not increased in postmenopausal women receiving EPTcc, whether women experienced bleeding or not. 37 The lack of change in MMPs 1, 3, 9, and 14 with EPTcc compared with progestin-only contraceptives implies differences in the etiology of bleeding in postmenopausal women receiving HT.…”

Section: Metalloproteinasesmentioning

confidence: 96%

Endometrial bleeding in postmenopausal women

Archer

2011

Menopause

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The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.

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Penicillins, cephalosporins, other beta-lactam antibiotics, and tetracyclines

Midtvedt¹

2011

Side Effects of Drugs Annual

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Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant

Cited by 12 publications

References 53 publications

Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity

Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity

Endometrial bleeding in postmenopausal women

Penicillins, cephalosporins, other beta-lactam antibiotics, and tetracyclines

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