ABSTRACT
Background: Polycystic ovary syndrome [PCOS] is a common complex genetic condition of women in the reproductive age. PCOS is a heterogeneous syndrome characterized by clinical/biochemical androgen excess, ovulatory dysfunction and polycystic ovaries. Metformin therapy has been proved to improve fertility in patients with PCOS, inducing not only high ovulation and pregnancy rates, but also reducing the incidence of miscarriages
Aim of the Work: This study was aimed to evaluate the effects of metformin therapy on hormonal profile and endometrial tissue, including pattern of immunohistochemical expression of androgen receptors [AR], in patients with PCOS
Patients and Methods: 100 patients with PCOS were included in this study. Each investigated case was submitted to detailed medical history, clinical examination that included body hair distribution, body weight, height and body mass index [BMI], transvaginal ultrasound, laboratory investigations [included fasting insulin, free testosterone, LH and FSH levels]. Endometrial pipelle samples were taken for histopathological evaluation and assessment of androgen receptor expression. These investigations were done before and after three months of metformin treatment
Results: A significant decrease of BMI of the investigated cases after metformin therapy was observed [P value <0.003]. There was a significant decrease of LH level after metformin therapy from 9.17 +/- 2.84 Miu/ml to 6.18 +/- 3.6 Miu/ml and of fasting insulin level from 14.3 +/- 4.3 to 8.2 +/- 5.9. Insignificant increase of FSH level from 3.87 +/- 1.8 to 4.85 +/- 2.6 and also insignificant decrease of free testosterone level from 1.58 +/- o.83 to 1.38 +/- 1.4 were also observed. Histopathological results of the endometrial specimens before metformin therapy revealed histologic features of early proliferative endometrium in 64 cases, 20 cases with a late proliferative endometrium and examination of the remaining 16 cases revealed features of simple endometrial hyperplasia. Among the 64 cases diagnosed as early proliferative endometrium before the therapy, 60 cases showed features of a late proliferative endometrium after treatment and the remaining 4 cases showed no histomorphologic changes. Among the 20 cases diagnosed as a late proliferative endometrium before therapy, 6 cases showed features of early secretory phase after therapy, 6 cases showed features of mid-secretory endometrium while the remaining 8 cases showed a late secretory endometrium that indicate successful ovulation after therapy. Regression of hyperplasia after therapy was noted in 6 of the 16 cases diagnosed as simple endometrial hyperplasia. Immunohistochemical [IHC] results revealed marked increase in endometrial AR expression in patients with PCOS compared to the normal fertile controls [p<0.004]. Also, a significant decrease of AR expression in endometrial epithelial and stromal cells after metformin administration in patients with PCOS was noted [p<0.003]
Conclusion: Metformin therapy restores normal menstrual cyclicity in patients with PCOS, induces ovulation and showing significant decrease in endometrial AR expression
ABSTRACT
Objective: To evaluate the effects of tissue-specific tibolone and continuous combined hormone replacement therapy [ccHRT] on mammographic parenchymal density and plasma lipoprotein profile in healthy postmenopausal women
Design and Setting: This was a prospective double-blind, randomised placebo-controlled study conducted at Al-Azhar University Hospitals in Damietta and Cairo
Subjects and Methods: 90 healthy postmenopausal women aged 48 to 55 years with a normal mammogram and lipid profile at baseline were equally randomized to receive one of three treatment arms: [1] tibolone 2.5 mg [group I. n=30]; [2] continuous combined 17-beta estradiol 2 mg plus norethisterone acetate 1 mg [E2/NETA] [group II, n=30]; [3] placebo [group III, n=30]. Mammograms were performed at baseline and after 12 months of treatment. Mammographic density was quantified according to the Wolfe classification and by the percentage area of the breast that had a dense pattern. Plasma levels of total cholesterol, low-density lipoprotein [LDL-C], high- density lipoprotein [HDL-C] cholesterol; triglycerides [TG]; lipoprotein [a] [Lp[a]]; apolipoprotein A [apoLpA] and apolipoprotein B [apoLpB] were determined on four occasions [i.e., baseline. 3-, 6- and 12-month visits]
Results: An increase in mammographic density was much more common among women receiving continuous combined hormone replacement therapy [43% - 50%] than among those receiving tibolone [3% - 6%] and placebo [0%] treatment. The difference between E2 /NETA and placebo was highly significant [p[c]<0.001]. Treatment with tibolone did not differ from that with placebo. In the tibolone group, 6% 13% of the women showed an involutionary change in breast density in the 12-month reevaluation. In contrast, none of the women receiving E2/NETA or placebo showed an involutionary changes in breast density. Considering the effects of treatment regimens on lipids profile, it was found that tibolone therapy was associated with a statistically significant reduction in serum triglycerides, HDL-C, apolipoprotein A and lipoprotein [a] by [22%, 20%. 10%. 20%, respectively] [p[a] <0.05], whilst no significant changes were seen in LDL-C and apolipoprotein B levels. In E2/NETA-group, there was a significant reduction of total cholesterol, LDL-C ,apolipoprotein B. HDL-C and lipoprotein [a] by [9%. 11%. 10.7%. 7.4%. 18%. respectively] [p[a] <0.05], whilst no significant changes were seen in triglycerides levels [p[a] >0.05]. Decrements were observed within 3 months of active treatments and maintained thereafter. Group I showed a more pronounced reduction of HDL-C, apolipoprotein A and triglycerides than Group II and Group III. The levels of LDL-C and apolipoprotein B declined significantly only in Group II [P[a] <0.05], while LDL-C/HDL-C ratio increased significantly in Group I by 23% when compared with GII [2.3%] and GIII [10.2%] after 12 months of treatment [P[b] and P[c]<0.05]
Conclusion: An increase in mammographic parenchymal density should be regarded as an unwanted side effect of HRT. In contrast to conventional estrogen/progestogen treatment, tissue-specific tibolone seems to exert little stimulation of breast tissue with no impairment of mammogram interpretation. Both tibolone and continuous combined HRT induced a favorable plasma lipid response. These therapeutic effects may contribute to the reduction or prevention of atherogenesis in postmenopausal women. Larger longterm studies are needed to confirm the impact of prolonged tibolone or continuous combined HRT administration on mammography and plasma lipoproteins