The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium

Roopa, B; Loganath, A.; Singh, Kuldip

doi:10.1093/humrep/deg329

Cited by 29 publications

(26 citation statements)

References 67 publications

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“…In addition to the proliferation of endometrial glands and stroma, EGF, and EGF-R may also be involved in the control of endometrial angiogenesis during the menstrual cycle (10). Clinical evidence suggests that the expression of angiogenic factors in the endometrial vessels increases under strong progestin stimulation, as observed in levonorgestrel intrauterine system users (24), and this concept may be expanded to EGF-R as suggested by the present study. Thus, EGF-R is a candidate mediator of progestin action in more than one target within the differentiating endometrium.…”

Section: Discussionsupporting

confidence: 59%

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

Reis

Lhullier

Edelweiss

et al. 2005

J Assist Reprod Genet

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Purpose : The present study evaluated the in vivo effect of medroxyprogesterone acetate (MPA) on the localization of immunoreactive transforming growth factor alpha (TGFα), epidermal growth factor (EGF), and their common receptor (EGF-R) in the human endometrium. Methods : The study design was a randomized clinical trial enrolling 36 healthy women with regular menstrual cycles. The participants were randomly assigned into three groups: groups 1 (n = 11) and 2 (n = 17) received placebo and were submitted to endometrial biopsy during the proliferative and secretory phases of menstrual cycle, respectively; group 3 (n = 8) received MPA (10 mg/day) for 10 days followed by endometrial biopsy, which was performed during the secretory phase. Immunohistochemistry was used to localize TGFα, EGF, and EGF-R in the endometrial tissue. Results : TGFα was present markedly in the luminal and glandular epithelia but also in the periglandular stroma, with a distribution pattern similar in the three experimental groups. EGF immunostaing was equally distributed in epithelial and stromal layers of the endometrium and remained unchanged in endometrial samples from women treated with MPA compared to placebo. EGF-R was expressed only in the epithelium. The intensity of EGF-R immunostaining was higher in secretory than in proliferative endometrium and was further increased by administration of MPA (p < 0.05, chi-square test). Conclusion : The present results suggest that the progestogen-induced in vivo differentiation of secretory endometrium does not require dramatic changes in the expression of EGF or TGFα, whereas EGF-R may be up regulated.

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Section: Discussionsupporting

confidence: 59%

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

Reis

Lhullier

Edelweiss

et al. 2005

J Assist Reprod Genet

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“…The LNG-IUS has been shown to cause an increase in VEGF levels in the endometrium at 3 and 6 months time points [50]. Importantly, this study demonstrated a positive correlation between changes in VEGF levels and clinically reported irregular bleeding, a correlation rarely shown in other studies.…”

Section: Progestogen Effects On Angiogenic Factorssupporting

confidence: 61%

Progestogen only contraception and endometrial break through bleeding

Smith

Critchley

2005

Angiogenesis

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Progestogen only contraceptives (POC) provide a safe and effective method of fertility regulation. Unfortunately, they are commonly associated with the problem of endometrial break through bleeding (BTB), often leading to discontinuation of use. An increase in endometrial vascular fragility has been demonstrated as an important mechanism that contributes to BTB but our understanding of the interaction between exogenous steroid use and endometrial vasculature remains incomplete. This review sets out to describe a number of commonly used POC, their effects on endometrial morphology and possible molecular and cellular mechanisms that may lead to unscheduled bleeding.

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“…Progesterone has been strongly linked with the production of basic fibroblastic growth factor (bFGF) in non-neuronal tissues such as the ovaries and uterus [15]. Furthermore, a norgestrelonly intrauterine release system significantly increases plasma and endometrial bFGF level [16]. In our recent publication, we observed norgestrel-mediated induction of bFGF, a neurotrophic factor repeatedly associated with protection from lightinduced photoreceptor degeneration, in the retina.…”

Section: Progestogens As Modulators Of Neuronal Survivalmentioning

confidence: 86%

Norgestrel may be a potential therapy for retinal degenerations

Doonan

Cotter

2012

Expert Opinion on Investigational Drugs

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The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium

Abstract: These results provide the first evidence that more than one angiogenic factor could be implicated in aberrant endometrial angiogenesis resulting in breakthrough bleeding in LNG-IUS acceptors.

Cited by 29 publications

References 67 publications

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

Progestogen only contraception and endometrial break through bleeding

Norgestrel may be a potential therapy for retinal degenerations

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