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The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study

Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al.

Gynecol Endocrinol, 2015 Apr;31(4):286-90.
PMID: 25495168 DOI: 10.3109/09513590.2014.989982

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.
A pilot study to determine whether progestogen supplementation using dydrogesterone during the first trimester will reduce the incidence of gestational hypertension in primigravidae

Zainul Rashid MR, Lim JF, Nawawi NH, Luqman M, Zolkeplai MF, Rangkuty HS, et al.

Gynecol Endocrinol, 2014 Mar;30(3):217-20.
PMID: 24552449 DOI: 10.3109/09513590.2013.860960

Gestational hypertension (GH) remains one of the main causes of high maternal and perinatal morbidity and mortality worldwide with the highest incidence among primigravidae of about 10%-15%. However, it was noted that the incidence of GH in primigravidae who conceived following assisted reproductive technique (ART) or intrauterine insemination (IUI) supplemented with dydrogesterone during the first trimester was low.

Study site: Obstetrics and Gynecology
Department, Pusat Perubatan Universiti Kebangsaan Malaysia PPUKM
Homeostatic indices of insulin resistance among gestational diabetics in anticipating pregnancy complications

Ismail NA, Kasim MM, Noor Aizuddin A, Umar NA

Gynecol Endocrinol, 2013 Jul;29(7):691-4.
PMID: 23772780 DOI: 10.3109/09513590.2013.797398

OBJECTIVE: This was to determine HOMA-IR score as well as to assess its association in fetal and maternal outcomes among pregnant women with diabetes risks.
METHODS: A prospective cohort study of pregnant women with diabetes risks was done. GDM was diagnosed using modified glucose tolerance test. Serum insulin was taken and measured by an electrochemiluminescence immunoassay method. Plasma glucose was measured by enzymatic reference method with hexokinase. HOMA-IR score was calculated for each patient. Maternal and fetal outcomes were analyzed.
RESULTS: From 279 women recruited, 22.6% had GDM with higher HOMA-IR score (4.07 ± 2.44 versus 2.08 ± 1.12; p = 0.001) and fasting insulin (16.76 ± 8.63 µIU/L versus 10.15 ± 5.07 µIU/L; p = 0.001). Area under ROC curve for HOMA-IR score was 0.79 (95% confidence interval, 0.74-0.84) with optimum cut-off value of 2.92 (sensitivity = 63.5%; specificity = 89.8%), higher than recommended by IDF (2.38). This point showed significant association with neonatal hypoglycemia (p = 0.02) and Cesarean section (p = 0.04) in GDM mothers.
CONCLUSIONS: HOMA-IR score and insulin resistance levels were higher in GDM women in our population. With the cut-off HOMA-IR value of 2.92, neonatal hypoglycemia and Cesarean section were significant complications in GDM mothers. This can be used in anticipation of maternal and fetal morbidities.
Reviewing the role of progesterone therapy in endometriosis

Abdul Karim AK, Shafiee MN, Abd Aziz NH, Omar MH, Abdul Ghani NA, Lim PS, et al.

Gynecol Endocrinol, 2019 Jan;35(1):10-16.
PMID: 30044157 DOI: 10.1080/09513590.2018.1490404

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.
Effectiveness of system-based intervention in reducing incidence of type 2 diabetes and to improve the postnatal metabolic profiles in women with gestational diabetes mellitus: a randomized controlled study

Lee KW, Tan SF, Omar A, Nasir NH, Ching SM, Mohd Noor MK, et al.

Gynecol Endocrinol, 2022 Jan;38(1):55-62.
PMID: 34636710 DOI: 10.1080/09513590.2021.1988561

AIM: The objective of this study was to determine the effectiveness of system-based intervention in reducing the incidence of diabetes and to improve the postnatal metabolic profiles among women with gestational diabetes mellitus (GDM).
MATERIALS AND METHODS: For women in the intervention arm (n = 130), they received one session of individualized health education at 36 gestational weeks, a booklet of diabetes prevention, five-session of postpartum booster educational program which were conducted including 1 session of dietary and exercise counseling by dietician and physiotherapist at 6 weeks postpartum. For women in the control group (n = 168), standard treatment whereby they had received group therapy on diet and physical activity modification by dietician and staff nurses during the antenatal period.
RESULTS: There were no significant differences in baseline characteristics between groups for most of the variables examined except for educational level which the control group had a higher education than the intervention group. The women assigned to system-based intervention have a significant difference to GDM women who were assigned to the control group for LDL and HDL but not in anthropometric measurements, blood pressure, glucose index, total cholesterol, and triglyceride. In addition, it was found that the incidence of Type 2 diabetes mellitus (T2DM) 2 years after delivery was 20% in the intervention arm compared to 17% in the control arm.
CONCLUSION: The system-based intervention was not statistically superior to the control intervention as there is no difference in terms of incidence of T2DM between the intervention and control group. We, therefore, suggested that more intensive interventions are needed to prevent GDM from developing into T2DM.