Therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of polycystic ovary syndrome

SUMMARY OBJECTIVE In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.

RESUMO OBJETIVO Tendo em vista a alta incidência de síndrome dos ovários policísticos (SOP) e os efeitos terapêuticos insatisfatórios da dimetildiguanida ou do citrato de clomifeno isoladamente, nosso estudo teve como objetivo investigar os efeitos terapêuticos da dimetildiguanida associada ao citrato de clomifeno no tratamento da SOP. MÉTODOS Um total de 79 pacientes com POCS e 35 mulheres saudáveis foram incluídos, e biópsias endometriais foram obtidas. A expressão da proteína de ligação do elemento regulador de esterol-1 (SREBP1) nos tecidos endometriais foi detectada por qRT-PCR. Pacientes POC foram divididos aleatoriamente em grupo A (n=40) e grupo B (n=39). Os pacientes do grupo A foram tratados com dimetildiguanida combinada com citrato de clomifeno, enquanto os pacientes do grupo B foram tratados apenas com citrato de clomifeno. O número de folículos maduros e muco cervical, taxa de desenvolvimento folicular e taxa de ovulação, taxa de gravidez, abortamento precoce, taxa de ovulação, espessura endometrial, taxa positiva de três linhas, nível de hormônio folículo estimulante e nível de hormônio luteinizante foram comparados entre os dois grupos. RESULTADOS O nível de expressão do SREBP1 foi maior nos pacientes com SOP do que no controle normal. A expressão de SREBP1 foi inibida após o tratamento, enquanto os efeitos inibidores do tratamento combinado foram mais fortes do que os do citrato de clomifeno isoladamente. Comparado com o citrato de clomifeno sozinho, o tratamento combinado melhorou significativamente a pontuação do muco cervical, a taxa de desenvolvimento folicular, a taxa de ovulação do folículo único, a espessura endometrial, a taxa positiva de três linhas de sinal e o nível de hormônio folículo estimulante. CONCLUSÃO O efeito terapêutico do tratamento combinado é melhor do que o citrato de clomifeno isolado no tratamento da SOP.

Luteal lifespan and fertility after estrus synchronization in goats

The present experiment aims to examine the efficiency of estrus synchronization using progesterone and equine chorionic gonadotrophin (eCG) and to look at luteal function. During the non-breeding and breeding season, 5 adult female Korean native goats were injected intramuscularly with 2.5 ml of physiological saline as the control. A progesterone impregnated intravaginal sponge was then kept in the same goats for 10 days followed, after a week, by an intramuscular injection of 500 IU eCG. Five adult female Nubian goats were mated with a fertile buck during the non-breeding season. During the non-breeding season 2 of the 5 goats showed a normal estrous cycle (ranging from 18 to 21 days) and 3 a short estrous cycle (ranging from 3 to 6 days). During the breeding season the equivalent figures were 1 and 2. The major axes of the corpus luteum (CL) were measured by means of calipers built into the ultrasonography system, and the concentrations of plasma progesterone (P(4)) were determined by double antibody radioimmunoassay. The mean major axes of the CL in goats showing the short cycle (6.1 +/- 0.5 mm) was significantly smaller than in those showing the normal cycle (8.9 +/- 0.5 mm; p < 0.01) and also the value of P4 in goats showing the short cycle (4.2 +/- 2.1 ng/ml) was significantly lower than for those showing the normal cycle (10.3 +/- 4.3 ng/ml; p < 0.05) at day 3 following ovulation. Three out of 5 Nubian goats became pregnant but only one goat carried to full term. The present experiment indicated that a combination of progesterone and eCG was effective in inducing estrus, although it resulted in a high incidence of short luteal lifespan. The low kidding rate and high incidence of embryonic loss may be due to the instability of the luteal lifespan.

GnRH and / or testosterone induced changes in reproductive activities during nonbreeding season in Calotes versicolor (Daud.).

Administration of Gonadotrophin releasing hormone (GnRH) to male C versicolor during nonbreeding season increases the weight of testis;diameter of testis, seminiferous tubule, Sertoli and Leydig cell nuclei. It also activates the spermatogenic process. Increase in the weight of epididymis and lowered cholesterol level of testis indicate androgen production. Treatment of tesotsterone along with GnRH further enhances the activities of testis as a few spermatozoa appeared in the lumen of seminiferous tubule along with increase in other spermatogenic elements. It may be concluded that the exogenous GnRH can induce reproductive activities during nonbreeding season when the environmental conditions are unfavourable. Testosterone administration has the additive effect on these activities.

Efficacy of laparoscopic ovulation induction in polycystic ovary syndrome.

This prospective study was aimed to evaluate the efficacy of laparoscopic ovarian electrocoagulation in women with PCOS. Twenty-three PCOS women who had refractory to clomiphene citrate attending the Reproductive Endocrinology Unit, Ramathibodi Hospital between March 1995 and June 1998 were enrolled in the study. In all patients, electrocoagulation on the ovarian surface of both ovaries was performed through laparoscope under general anesthesia. Two patients were lost to follow-up for unknown reasons. The remaining 21 women had a mean age of 30.3 +/- 3.9 years (range 21-39) and mean duration of infertility of 4.1 +/- 2.8 years (range 1-11). There was no intra-operative and post-operative complication. After surgery, ovulation was documented in 16 out of 18 (88.9%) patients. Fifteen (71.4%) patients became pregnant. Fourteen pregnancies (93.3%) occurred within 9 months after surgery. Twelve women (80%) became pregnant in spontaneous cycles without any treatment. The outcomes of pregnancies were 10 live births, 3 ongoing pregnancies and 2 abortions. This study reveals the high efficacy of ovarian electrocoagulation in infertile women with PCOS. High pregnancy and low abortion rates are convincing. This surgical technique should be the treatment of choice for women with CC-resistant PCOS.

Induction Of ovulation.

Sixty-one patients with anovulation as a cause of infertility were selected for our study. Various ovulation-inducing drugs were used like clomiphene citrate, human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG), bromergocryptine and leptadene. The response of the different drugs was observed by serial sonography for ovulation. Indeed there was a good response to clomiphene citrate, but those patients who failed to respond to clomiphene citrate and were frustrated with the use of hMG and hCG due to the cost and the complications of the therapy were put on Aloe compound and leptadene - an ayurvedic drug which enhances fertility in different ways.

Antiestrogênios / Antiestrogens

Os antiestrogênios podem ser utilizados atualmente como terapêutica adjuvante em pacientes acometidos pelo câncer de mama. É apresentada uma revisäo dos principais aspectos e das características farmacológicas e clínicas dos antiestrogênios