Serum Androgen Profiles In Women With Premature Ovarian Insufficiency:A Systematic Review And Meta-analysis

PART I:A systematic review and meta-analysis on serum androgen profiles in women with premature ovarian failure VS fertile controlsBackground:Premature ovarian failure(POF)or premature ovarian insufficiency(POI)is a woman’s pathological state,in which the woman’s ovaries stop working before the age of 40 years old.Due to complete premature ovarian insufficiency,POF/POI patients suffer from amenorrhea infertility and other menopause-related symptoms,such as hot flushes,night sweats,vaginal dryness,the increased risk of overall mortality,cardiovascular diseases,neurological diseases,psychiatric diseases,psychological distress,osteoporosis,reduced sexual arousal,muscle weakness,etc.Most of these symptoms in POF/POI patients could be explained as resulting from hypoestrogenism,but not all.Some studies have indicated that some symptoms in POF/POI patients,like psychiatric diseases,psychological distress,reduced sexual arousal,muscle weakness,etc.,may be due to diminished testosterone levels.Diminished Androgen levels are a possible feature in patients with POF/POI.Objective:This meta-analysis aims to investigate serum androgen profiles(testosterone,Dehydroepiandrosterone sulfate,Androstenedione and Sex hormone-binding globulin)in women with premature ovarian msufficiency and comparing them to fertile controls to and to make sure if there is an increased risk for diminished androgen levels in these patients.Methods:Various Internet sources of PubMed,Cochrane library and Medline were searched systematically until February 2018.Out of a pool of 2461 studies,after applying the inclusion/exclusion criterion,14,8,10,9 studies were chosen for Testosterone,Dehydroepiandrosterone sulfate,Androstenedione and Sex hormone-binding globulin respectively for this Meta-analysis.The effect measure was the standardized mean difference with 95%confidence interval(95%CI)in a random effects model.Results:The Testosterone concentrations in premature ovarian insufficiency(n=937)compared to fertile controls(n=719):Std.Mean Difference(IV,Random,95%CI)-0.73[-0.99,-0.46],p-value<0.05.The Dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency(n=458)compared to fertile controls(n=453):Std.Mean Difference(IV,Random,95%CI)-0.65[-0.92,-0.37],p-value<0.05.Androstenedione in premature ovarian insufficiency(n=697)compared to fertile controls(n=529):Std.Mean Difference(IV,Random,95%CI)-1.09[-1.71,-0.48],p-value<0.05.Sex hormone-binding globulin levels(n=796)did not show statistical significance.Conclusions:Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone,Dehydroepiandrosterone sulfate and Androstenedione.PART II:A systematic review and meta-analysis on serum androgen profiles in women with premature ovarian failure VS Postmenopausal controlsBackground:It has not been clear if there is a decrease in androgen levels for women with POF/POI.It is clear that,at the present,the state of spontaneous POF/POI is different from the natural menopausal process.Many studies have shown evidence that there is a gradual decline in circulating serum androgen levels as women age and that there is no independent effect of natural menopause causing a further reduction.If there is indeed a clinically significant reduction in Androgen levels,Androgen replacement therapy could be considered to augment the standard estrogen-based hormone therapy for women with POF/POI,but this needs to be further investigated.Some studies have shown that there was a positive correlation between serum Androgen concentration’s in women with POF/POI to age.POF/POI is a pathologic condition in which women have lower serum estradiol levels as compared with other women of similar age.It is yet to be known if women with POF/POI presents with lower androgen levels when compared with menopausal women.Objective:This meta-analysis aims to investigate serum androgen profiles(testosterone,Dehydroepiandrosterone sulfate,Androstenedione in women with premature ovarian insufficiency and comparing them to postmenopausal controls to and to establish if there is an increased risk for diminished androgen levels in these patients.Methods:Various Internet sources of PubMed,Cochrane library and Medline were searched systematically until February 2018.Out of a pool of 2461 studies,after applying the inclusion/exclusion criterion,3 studies were chosen for Testosterone,Dehydroepiandrosterone sulfate,Androstenedione for this Meta analysis.The effect measure was the standardized mean difference with 95%confidence interval(95%CI)in a random effects model.Results:The total serum testosterone concentrations of POF/POI patients(n=233)vs.postmenopausal controls(n=232)showed a Std.Mean Difference-0.05[-0.68,0.58].The dehydroepiandrosterone sulfate concentrations of POF/POI patients(n=233)vs.postmenopausal controls(n=232)showed a Std.Mean Difference 1.12[0.10,2.14],p-value<0.05.The androstenedione concentrations of POF/POI patients(n=233)vs.postnmenopausal controls(n=232)showed a Std.Mean Difference 0.27[-0.13,0.67].Conclusions:It was only for dehydroepiandrosterone sulfate that a significant decrease was noted in the postmenopausal group when comparing testosterone,dehydroepiandrosterone sulfate and androstenedione between POF/POI women and the post-menopausal group.The reasons for a significant decrease of dehydroepiandrosterone sulfate seen in the postmenopausal group could be due to aging...