Long-term effects of combined simvastatin and metformin treatment on the clinical abnormalities and ovulation dysfunction in single young women with polycystic ovary syndrome

AbstractPolycystic ovary syndrome (PCOS) is a complex disorder which interacts with other genetic and environmental factors to cause dysregulation of steroidogenesis and anovulation as well as insulin resistance. Treatments which address the long-term effects of this unique combination of reproductive and metabolic dysfunction are needed. Over the past decade, new insights into the genetic factors of PCOS and biotechnological advances have led to potential treatments for women with PCOS. These treatments include both new potent pharmaceutical compounds and repurposed drugs which target different steps in metabolic-reproductive pathways to improve long-term health of women with PCOS. These new therapies target key enzymes involved in steroidogenesis, regulatory pathways of gonadotropin secretion, or lower oxidative stress. We review in this article the current common treatments of PCOS, recent developments in the field, and current information on the mode of action, efficacy, and safety of emerging therapeutic compounds.

Download Full-text

Polycystic Ovary Syndrome: Long-term Effects

Annals of Medicine ◽

10.3109/07853899309147289 ◽

1993 ◽

Vol 25 (4) ◽

pp. 307-308 ◽

Cited By ~ 2

Author(s):

Eva Dahlgren ◽

Per Olof Janson

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Long Term Effects ◽

Ovary Syndrome

Download Full-text

Metformin administration improves endothelial function in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.01910 ◽

2005 ◽

Vol 152 (5) ◽

pp. 749-756 ◽

Cited By ~ 112

Author(s):

E Diamanti-Kandarakis ◽

K Alexandraki ◽

A Protogerou ◽

C Piperi ◽

C Papamichael ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Young Women ◽

Polycystic Ovary ◽

Biological Marker ◽

Control Group ◽

Metformin Treatment ◽

Mathematical Methods ◽

Ovary Syndrome ◽

Pcos Group ◽

Normal Women

Objective: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. Design: Descriptive clinical trial. Methods: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. Results: FMD was impaired in the PCOS group when compared with controls (3.24±0.71% vs 8.81±1.07% respectively, P < 0.0001), but this difference normalized after metformin treatment (PCOSpost-metformin vs controls: 8.17±1.26 vs 8.81±1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOSpre-metformin vs PCOSpost-metformin: 3.24±0.71 vs 8.17±1.26%, P = 0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23±0.50 vs 4.99±0.69 fmol/l, P = 0.01), they improved significantly after metformin treatment (PCOSpre-metformin vs PCOSpost-metformin: 7.23±0.50 vs 3.57±0.60 fmol/l, P < 0.0001) and their difference compared with the control group was reversed (PCOSpost-metformin vs controls: 3.57±0.60 vs 4.99±0.69 fmol/l, P = 0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. Conclusions: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Download Full-text

The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.0.1440619 ◽

2001 ◽

Vol 144 (6) ◽

pp. 619-628 ◽

Cited By ~ 47

Author(s):

J Vrbikova ◽

M Hill ◽

L Starka ◽

D Cibula ◽

B Bendlova ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Hydroxysteroid Dehydrogenase ◽

Gnrh Analogue ◽

Metformin Treatment ◽

Ovary Syndrome ◽

Ovarian Steroidogenesis ◽

Long Term Treatment ◽

Before And After

OBJECTIVE: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. RESULTS: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01). CONCLUSIONS: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

Download Full-text

Long‐term health outcomes in young women with Polycystic Ovary Syndrome: a narrative review

Clinical Endocrinology ◽

10.1111/cen.14609 ◽

2021 ◽

Author(s):

Lowri A. Allen ◽

Natasha Shrikrishnapalasuriyar ◽

D. Aled Rees

Keyword(s):

Polycystic Ovary Syndrome ◽

Health Outcomes ◽

Young Women ◽

Polycystic Ovary ◽

Narrative Review ◽

Ovary Syndrome

Download Full-text

Long-term effects of a three-component lifestyle intervention on emotional well-being in women with Polycystic Ovary Syndrome (PCOS): A secondary analysis of a randomized controlled trial

PLoS ONE ◽

10.1371/journal.pone.0233876 ◽

2020 ◽

Vol 15 (6) ◽

pp. e0233876

Author(s):

Geranne Jiskoot ◽

Alexandra Dietz de Loos ◽

Annemerle Beerthuizen ◽

Reinier Timman ◽

Jan Busschbach ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Controlled Trial ◽

Secondary Analysis ◽

Well Being ◽

Long Term Effects ◽

Ovary Syndrome ◽

Randomized Controlled

Download Full-text

The efficacy of long-term metformin treatment in women with polycystic ovary syndrome

Fertility and Sterility ◽

10.1016/j.fertnstert.2017.07.738 ◽

2017 ◽

Vol 108 (3) ◽

pp. e245-e246

Author(s):

M. Chen ◽

P. Yang ◽

H. Chen ◽

S. Chen ◽

H. Ho

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Metformin Treatment ◽

Ovary Syndrome

Download Full-text

Cholesterogenic Effects of Whey Protein Isolate Supplementation in Women with Polycystic Ovary Syndrome

Current Developments in Nutrition ◽

10.1093/cdn/nzaa047_001 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 581-581

Author(s):

Shenavia Balcom-Luker ◽

Kayleigh Kaiser ◽

Irene Low ◽

Emily Zumbro ◽

K Shane Broughton ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Total Cholesterol ◽

Whey Protein ◽

Polycystic Ovary ◽

Whey Protein Isolate ◽

Protein Isolate ◽

Long Term Effects ◽

Ovary Syndrome ◽

Short And Long Term

Abstract Objectives The current study examined the short- and long-term effects of whey protein isolate ingestion on circulating Low-Density Lipoprotein (LDL) and total cholesterol (TC) concentrations in women with polycystic ovary syndrome (PCOS). PCOS is a disorder characterized by reproductive, metabolic and endocrine disruption in women of reproductive age. Nutritional management options are limited. Whey protein isolate (WPI) improves metabolic parameters in patients with type 2 diabetes, but its therapeutic potential in polycystic women has yet to be realized. Women with PCOS have altered metabolic profiles and are more likely to develop liver disorders such as non-alcoholic fatty liver disease (NAFLD). Given the association between PCOS and NAFLD, we hypothesized that supplementation with WPI may attenuate circulating LDL and TC in a polycystic population. Methods Fifteen premenopausal women with PCOS and fourteen healthy, regularly menstruating women underwent three 150-min oral glucose tolerance tests (OGTT): (i) OGTT without protein preload, (ii) OGTT on 20th, and (iii) 40th day of protein preload. Participants consumed 35g protein daily with protein intake 30 min before carbohydrate load on test days. Plasma levels of LDL and total cholesterol were assessed at baseline, day 20 and day 40 to determine short- and long-term effects using a Biolis 24i chemistry analyzer. (Participant recruitment, data collection and analyses in progress.) Results Preliminary data indicates that time and condition (PCOS vs control) did not have a significant effect on LDL or TC levels within and between groups (P > .05). However, disease condition had a significant impact on LDL (P < .001) and TC (P = .001) concentrations. Changes in LDL and TC levels after 40 days of protein preload are currently being analyzed. Conclusions Women with PCOS have higher levels of LDL and TC than those without this condition. While short-term effects of 35g WPI ingestion do not seem to alter these levels, a longer duration of supplementation may induce more beneficial effects (currently being conducted). Findings from this study may provide foundational support for WPI as a nutritional treatment for women with PCOS. Funding Sources Glanbia Nutritionals, INC and Human Nutrition Research Funds, Texas Woman's University.

Download Full-text