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Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.

Abstract Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.
PMID
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Authors

Mayor MeshTerms
Keywords

endometrial cancer

gestational diabetes

metformin

obesity in pregnancy

polycystic ovary syndrome

Journal Title human reproduction update
Publication Year Start
%A Sivalingam, Vanitha N.; Myers, Jenny; Nicholas, Susie; Balen, Adam H.; Crosbie, Emma J.
%T Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.
%J Human reproduction update, vol. 20, no. 6, pp. 853-868
%D 11/2014
%V 20
%N 6
%M eng
%B Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.
%K Clomiphene, Diabetes, Gestational, Endometrial Neoplasms, Female, Genital Neoplasms, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Life Style, Metformin, Ovulation, Ovulation Induction, Polycystic Ovary Syndrome, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Reproductive Health
%P 853
%L 868
%Y 10.1093/humupd/dmu037
%W PHY
%G AUTHOR
%R 2014.......20..853S

@Article{Sivalingam2014,
author="Sivalingam, Vanitha N.
and Myers, Jenny
and Nicholas, Susie
and Balen, Adam H.
and Crosbie, Emma J.",
title="Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.",
journal="Human reproduction update",
year="2014",
month="Nov/Dec",
day="10",
volume="20",
number="6",
pages="853--868",
keywords="Clomiphene",
keywords="Diabetes, Gestational",
keywords="Endometrial Neoplasms",
keywords="Female",
keywords="Genital Neoplasms, Female",
keywords="Humans",
keywords="Hypoglycemic Agents",
keywords="Insulin Resistance",
keywords="Life Style",
keywords="Metformin",
keywords="Ovulation",
keywords="Ovulation Induction",
keywords="Polycystic Ovary Syndrome",
keywords="Pregnancy",
keywords="Pregnancy Outcome",
keywords="Pregnancy Rate",
keywords="Reproductive Health",
abstract="Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.",
issn="1460-2369",
doi="10.1093/humupd/dmu037",
url="http://www.ncbi.nlm.nih.gov/pubmed/25013215",
language="eng"
}

%0 Journal Article
%T Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.
%A Sivalingam, Vanitha N.
%A Myers, Jenny
%A Nicholas, Susie
%A Balen, Adam H.
%A Crosbie, Emma J.
%J Human reproduction update
%D 2014
%8 Nov/Dec 10
%V 20
%N 6
%@ 1460-2369
%G eng
%F Sivalingam2014
%X Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.
%K Clomiphene
%K Diabetes, Gestational
%K Endometrial Neoplasms
%K Female
%K Genital Neoplasms, Female
%K Humans
%K Hypoglycemic Agents
%K Insulin Resistance
%K Life Style
%K Metformin
%K Ovulation
%K Ovulation Induction
%K Polycystic Ovary Syndrome
%K Pregnancy
%K Pregnancy Outcome
%K Pregnancy Rate
%K Reproductive Health
%U http://dx.doi.org/10.1093/humupd/dmu037
%U http://www.ncbi.nlm.nih.gov/pubmed/25013215
%P 853-868

PT Journal
AU Sivalingam, VN
   Myers, J
   Nicholas, S
   Balen, AH
   Crosbie, EJ
TI Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.
SO Human reproduction update
JI Hum. Reprod. Update
PD Nov/Dec
PY 2014
BP 853
EP 868
VL 20
IS 6
DI 10.1093/humupd/dmu037
LA eng
DE Clomiphene; Diabetes, Gestational; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Metformin; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Reproductive Health
AB Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.
ER

PMID- 25013215
OWN - NLM
STAT- MEDLINE
DA  - 20141015
DCOM- 20150501
LR  - 20150105
IS  - 1460-2369 (Electronic)
IS  - 1355-4786 (Linking)
VI  - 20
IP  - 6
DP  - 2014 Nov-Dec
TI  - Metformin in reproductive health, pregnancy and gynaecological cancer:
      established and emerging indications.
PG  - 853-68
LID - 10.1093/humupd/dmu037 [doi]
AB  - BACKGROUND: Metformin is an effective oral anti-hyperglycaemic drug used as
      first-line medical treatment for type 2 diabetes. It improves systemic
      hyperglycaemia by reducing hepatic glucose production and enhancing peripheral
      insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis
      and storage. The molecular mechanism of this drug is thought to be secondary to
      its actions on the mitochondrial respiratory chain. METHODS: This paper reviews
      the relevant literature (research articles up to October 2013) on the use of
      metformin in infertility, polycystic ovary syndrome (PCOS), pregnancy and
      gynaecological cancers. We present a comprehensive discussion of the evidence
      supporting the efficacy of metformin in these clinical conditions. RESULTS:
      Metformin is used clinically off-label in the management of hirsutism, acne and
      insulin resistance in PCOS, although the evidence for anti-androgenic effects is 
      inconsistent. Metformin is also used to improve ovulation in women with PCOS both
      alone and in combination with clomiphene citrate. Trial findings are conflicting 
      but metformin treatment in IVF/ICSI cycles may reduce the risk of ovarian
      hyperstimulation syndrome and increase live birth rates. Metformin also appears
      to be effective and safe for the treatment of gestational diabetes mellitus
      (GDM), particularly for overweight and obese women. Studies have shown that
      metformin is safe in pregnancy and women with GDM treated with metformin have
      less weight gain during pregnancy than those treated with insulin. One study with
      a 2-year follow-up demonstrated that babies born to women treated with metformin 
      also developed less visceral fat, making them less prone to insulin resistance in
      later life. These findings have sparked interest in the use of metformin for
      pregnant, obese, non-diabetic women. On-going clinical trials are underway to
      determine if women treated prophylactically with metformin have a reduced
      incidence of GDM and demonstrate less weight gain during pregnancy. The
      hypothesis in these studies is that babies born to obese women on prophylactic
      metformin will also have better outcomes. Epidemiological studies have linked
      metformin exposure to a decreased risk of cancer. Pre-clinical experiments report
      that metformin has a growth-static effect on several cancers, including
      endometrial cancer, which may be partly due to the effect of metformin on the
      PI3K/AKT/mTOR signal transduction pathway. A number of on-going early phase
      clinical trials aim to explore the anti-cancer effects of metformin and
      investigate its potential as a chemopreventative or adjuvant treatment.
      CONCLUSIONS: Obesity is on the rise in developing countries and is strongly
      linked to several reproductive health problems, including PCOS, GDM and
      endometrial cancer. Traditional lifestyle measures aimed at weight reduction are 
      challenging to implement and maintain. Metformin may be a valuable alternative
      to, or adjunct for, modifying the toxic effects of obesity in these populations. 
      This review will appraise the evidence for the use of metformin for the
      prevention and treatment of adverse health outcomes in obstetrics and
      gynaecology.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the
      European Society of Human Reproduction and Embryology. All rights reserved. For
      Permissions, please email: [email protected]
FAU - Sivalingam, Vanitha N
AU  - Sivalingam VN
AD  - Institute of Cancer Sciences, Manchester Academic Health Science Centre,
      University of Manchester, Central Manchester University Hospitals NHS Foundation 
      Trust, Oxford Road, Manchester M13 9WL, UK.
FAU - Myers, Jenny
AU  - Myers J
AD  - Institute of Human Development, Manchester Academic Health Science Centre,
      University of Manchester, Central Manchester University Hospitals NHS Foundation 
      Trust, Oxford Road, Manchester M13 9WL, UK.
FAU - Nicholas, Susie
AU  - Nicholas S
AD  - Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Seacroft
      Hospital, Leeds LS14 6UH, UK.
FAU - Balen, Adam H
AU  - Balen AH
AD  - Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Seacroft
      Hospital, Leeds LS14 6UH, UK.
FAU - Crosbie, Emma J
AU  - Crosbie EJ
AD  - Institute of Cancer Sciences, Manchester Academic Health Science Centre,
      University of Manchester, Central Manchester University Hospitals NHS Foundation 
      Trust, Oxford Road, Manchester M13 9WL, UK [email protected]
LA  - eng
GR  - NIHR-CS-012-009/Department of Health/United Kingdom
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140710
PL  - England
TA  - Hum Reprod Update
JT  - Human reproduction update
JID - 9507614
RN  - 0 (Hypoglycemic Agents)
RN  - 1HRS458QU2 (Clomiphene)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Clomiphene/therapeutic use
MH  - Diabetes, Gestational/drug therapy
MH  - Endometrial Neoplasms/drug therapy/prevention & control
MH  - Female
MH  - Genital Neoplasms, Female/*drug therapy/prevention & control
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use
MH  - Insulin Resistance/physiology
MH  - Life Style
MH  - Metformin/adverse effects/pharmacology/*therapeutic use
MH  - Ovulation/drug effects
MH  - Ovulation Induction
MH  - Polycystic Ovary Syndrome/drug therapy
MH  - Pregnancy
MH  - Pregnancy Outcome
MH  - Pregnancy Rate
MH  - Reproductive Health
OTO - NOTNLM
OT  - endometrial cancer
OT  - gestational diabetes
OT  - metformin
OT  - obesity in pregnancy
OT  - polycystic ovary syndrome
EDAT- 2014/07/12 06:00
MHDA- 2015/05/02 06:00
CRDT- 2014/07/12 06:00
PHST- 2014/07/10 [aheadofprint]
AID - dmu037 [pii]
AID - 10.1093/humupd/dmu037 [doi]
PST - ppublish
SO  - Hum Reprod Update. 2014 Nov-Dec;20(6):853-68. doi: 10.1093/humupd/dmu037. Epub
      2014 Jul 10.
TY  - JOUR
AU  - Sivalingam, Vanitha N.
AU  - Myers, Jenny
AU  - Nicholas, Susie
AU  - Balen, Adam H.
AU  - Crosbie, Emma J.
PY  - 2014/Nov/Dec/10
TI  - Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications.
T2  - Hum. Reprod. Update
JO  - Human reproduction update
SP  - 853
EP  - 868
VL  - 20
IS  - 6
KW  - Clomiphene
KW  - Diabetes, Gestational
KW  - Endometrial Neoplasms
KW  - Female
KW  - Genital Neoplasms, Female
KW  - Humans
KW  - Hypoglycemic Agents
KW  - Insulin Resistance
KW  - Life Style
KW  - Metformin
KW  - Ovulation
KW  - Ovulation Induction
KW  - Polycystic Ovary Syndrome
KW  - Pregnancy
KW  - Pregnancy Outcome
KW  - Pregnancy Rate
KW  - Reproductive Health
N2  - Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain.
SN  - 1460-2369
UR  - http://dx.doi.org/10.1093/humupd/dmu037
UR  - http://www.ncbi.nlm.nih.gov/pubmed/25013215
ID  - Sivalingam2014
ER  - 
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