The Impact of Irregular Menstruation on Health: A Review of the Literature.

Women are considered to have an irregular menstrual cycle if their cycle length is less than 21 days or more than 35 days, accompanied by less or very severe blood flow. The prevalence of menstrual cycle irregularities varies across countries. Irregular periods can occur due to changes in the body's levels of estrogen and progesterone hormones, which disrupt the normal pattern of the period. Menstrual irregularity has been found to be associated with various diseases and medical conditions, such as metabolic syndrome, coronary heart disease, type 2 diabetes mellitus, and rheumatoid arthritis. Anemia, osteoporosis, psychological problems, impaired quality of life, and infertility have also been recorded. Moreover, a significant correlation between irregular periods and the risk of developing pregnancy-related hypertensive disorders, as well as an increased risk of adverse obstetric and neonatal outcomes, has been proven. Therefore, irregular menstruation is considered an important health indicator among women. Physical, mental, social, psychological, and reproductive problems are often associated with menstrual irregularities. Thus, evaluating the factors associated with irregular menstruation is necessary to determine appropriate preventive and treatment strategies and to decrease the associated health problems. The aim of this review was to define normal and irregular menstruation, their types, and prevalence, to recognize the risk factors and causes of irregular menstruation, and to understand their impact on women's health.

Role of Metformin in Polycystic Ovary Syndrome (PCOS)-Related Infertility.

Polycystic ovarian syndrome (PCOS) is considered the most prevalent endocrinological disorder, which affects some women and it is characterized by anovulation and hyperandrogenism, with morphologic changes in the ovary, inappropriate gonadotropin secretion, and insulin resistance (IR) with accompanying compensatory hyperinsulinemia. PCOS was associated with some degree of IR which probably contributes to hyperandrogenism. Many studies showed that metformin, when used to treat PCOS, significantly reduced serum androgen levels, improved insulin sensitivity, restored menstrual cyclicity, and was successful in triggering ovulation. As a result, metformin may be useful in treating PCOS-related infertility. The aim of this review was to clarify PCOS, its prevalence, particularly in Saudi Arabia, its pathogenesis, its impact on the patient's health, and to explain the uses of metformin, its mechanism of action, and its role in the treatment of PCOS-related infertility.

Bone marrow-derived mesenchymal stem cells ameliorate parotid injury in ovariectomized rats.

BACKGROUND AIMS: Parotid hypofunction causes life-disrupting effects, and there are no effective medications for xerostomia. We hypothesized that mesenchymal stem cells (MSCs) have repairing effects on parotid glands of ovariectomized (OVX) rats. METHODS: Forty-five adult female rats were divided into three equal groups: group I (Control group), group II (OVX-group) and group III (OVX rats that received MSCs at 4 and 8 weeks post-ovariectomy). At 12 weeks post-ovariectomy, histological (Masson's trichrome and periodic acid-Schiff with alcian blue stains), immunohistochemical (caspase-3 and CD44) and morphometric studies and salivary flow rate and saliva pH determination were carried out. RESULTS: Histologically, the OVX group displayed numerous irregular vacuolated acini, thickened septa with marked cellular infiltration and vascular congestion. Degenerated organelles and few or irregular secretory granules with a different density were observed. Caspase-3-positive cells were highly expressed. MSC-treated glands exhibited a considerable degree of preservation of glandular architecture with numerous CD44-expressing and few caspase-3-expressing cells. Significant decrease of the salivary flow rate in the OVX group was detected, which reverted to normal levels in group III. CONCLUSIONS: MSCs ameliorated the damaging effects of ovariectomy on the parotid glands.

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-ß1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-ß1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-ß1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-ß1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-ß1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats.

Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into four groups; control, TMZ, CSP, and CSP + TMZ. The CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage, glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis, and inflammatory cell infiltrates, all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde (MDA) levels, renal nuclear factor kappa B (NF-κB) DNA-binding activity and protein expression, and tumor necrosis factor alpha (TNF-α) and IL-6 levels. Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6 and NF-κB expression and its DNA-binding activity caused by CSP administration. TMZ has a protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress and attenuation of CSP-induced inflammation.

Beneficial effects of nilotinib, tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats.

Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A.

Enhanced expression of vascular endothelial growth factor and increased microvascular density in women with endometrial hyperplasia: a possible relationship with uterine natural killer cells.

This case-control study aimed to investigate the expression of natural killer cells (NKCs) and the integrated optical density (IOD) of vascular endothelial growth factor (VEGF) and to quantify microvascular density (MVD) in endometrial biopsies from women with endometrial hyperplasia (EH) relative to normal subjects. Histological data from four groups were analyzed. The study population included 30 women with simple EH without atypia, 25 patients with complex EH without atypia, 25 with complex EH with atypia and 25 healthy women with non-hyperplastic endometrium (control group). Paraffin sections were immunostained with antibodies against CD56, VEGF-A and CD34 using an Avidin-Biotin-Peroxidase technique. The evaluation of NKC density and IOD of VEGF expression and measurement of MVD were performed using light microscopy examination and image analysis techniques. Increased numbers of NKCs were documented in cases of complex EH with atypia compared with the other groups (p<0.001). The number of NKCs was lower in cases of hyperplasia without atypia compared with the controls, but the difference was not significant. The IOD of VEGF-A and MVD increased significantly with progression from the non-hyperplastic endometrium through the three groups of EH (p<0.001). We observed a significant correlation between the MVD and the IOD of VEGF-A in the studied groups (r=0.434; p<0.001). Additionally, NKCs density was correlated significantly with IOD of VEGF-A (r=0.661; p<0.001) and with the MVD (r=0.473; p<0.001). These results suggest that NKC-count, IOD of VEGF and endometrial MVD are all related to the histological changes of the endometrium and that endometrial hyperplasia exhibits distinct immunological backgrounds in the context of NKC infiltration and VEGF production.

Light and electron microscopic study on the effect of antischizophrenic drugs on the structure of seminiferous tubules of adult male albino rats.

INTRODUCTION: Sexual dysfunction and infertility are symptoms which have been rarely studied in patients treated with antischizophrenic drugs, aripiprazole and olanzapine, for long period. This work aimed to investigate the effects of aripiprazole and olanzapine on the structure of seminiferous tubules of rats at both light microscopic and ultrastructural levels. MATERIAL AND METHODS: Sixty adult male rats were divided into 3 groups (n = 20): control group (Group I) and two experimental ones (II and III). Rats in Group II received 2 mg/kg/day aripiprazole while rats in Group III received 0.5 mg/kg/day olanzapine for 14 weeks. Thereafter, testis were removed and processed for both light and electron microscopic study. Qualitative morphological analyses and histomorphometric measurements of seminiferous tubules were performed. RESULTS: Rats in Group II showed reduction of testicular weight, seminiferous tubules' diameter, epithelial height, spermatogenic count, spermatogenic index and spermatogenic score whereas Sertoli cells count was increased. Olanzapine-treated rats also showed epithelial desquamation, separation and apoptotic changes of germ cells. Sertoli cells showed vacuolization, dilatation of smooth endoplasmic reticulum and accumulation of lipid droplets. Abnormality in the shape and structure of late spermatids and presence of giant cells were also demonstrated. Aripiprazole induced less adverse histological changes in rat testis than olanzapine. CONCLUSIONS: Olanzapine followed by aripiprazole had adverse histological effects on the structure of the seminiferous tubules, which may affect spermatogenesis.