Efficacy and safety of 17alpha-hydroxyprogesterone caproate in hormone replacement therapy.

The aim of the present study was to evaluate the efficacy (in terms of induction of uterine bleeding) and safety (in terms of absence of endometrial hyperplasia) of 17alpha-hydroxyprogesterone caproate (17alpha-HPC) in a therapeutic regimen for hormonal replacement after menopause. Fifty postmenopausal patients received hormone replacement therapy (HRT) for 24 weeks. The treatment regimen consisted of standard estrogen replacement therapy at commonly prescribed doses for the prevention of climacteric symptoms and 341 mg of 17alpha-HPC every 30 days. Enrolled women were told to expect withdrawal bleeding 7-10 days after the administration of 17alpha-HPC. Forty-eight patients completed the trial. In 91.7% of cases, patients experienced the expected pattern, i.e., strict withdrawal bleeding exclusive of any other form of bleeding. Breakthrough bleeding and/or other forms of abnormal bleeding affected only four women. At the 6th month none of the endometrial samplings motivated by endometrial thickness >10 mm and evidence of heterogeneous echogenicity (two cases) was positive for carcinoma. No biopsies had to be performed at the end of the 12th month of treatment. No serious adverse effect where recorded during the study period. In conclusion, our data show the efficacy and safety of 17alpha-HPC in HRT.

Diclofenac pyrrolidine versus Ketoprofen for the relief of pain from episiotomy: a randomized controlled trial.

BACKGROUND: The treatment of pain from episiotomy or from tearing of perineal tissues during childbirth is often unapplied, although discomfort may be severe. We performed a randomized double-blind controlled trial to compare the effectiveness and side-effects of two analgesics in the management of postpartum perineal pain. Patient preference toward the two medications was also analyzed. METHODS: A total of 261 women were randomly assigned to receive either Diclofenac hydroxyethyl pyrrolidine (100 mg) (n = 133) or Ketoprofen (100 mg) (n = 128), both given orally every 12 hr up to 48 hr, as necessary. Inclusion criteria were vaginal birth with episiotomy and/or a second- to third-degree tear. Pain ratings were recorded before the administration of the drugs and at 1, 4, 12, and 24 hr after the first dose, according to a 10-cm visual-analog scale. Side-effects and overall opinion on the two treatments were assessed at 24 hr. RESULTS: Diclofenac hydroxyethyl pyrrolidine and Ketoprofen had similar analgesic properties in the first 24 hr postpartum [mean pain rating 3.1 +/- 1.8 and 3.4 +/- 2.0, mean number of doses in 24 hr 1.4 +/- 1.4 and 1.3 +/- 1.5, and proportion of treatment failures 12.8% (17/133) and 16.4% (21/128), respectively]. Significantly fewer subjects in the Diclofenac hydroxyethyl pyrrolidine group than in the Ketoprofen group experienced side-effects (6.8% versus 15.6%; p = 0.038) with an odd risk = 0.39(95% C.I. 0.16-0.95). There were no significant differences in overall patient satisfaction between the two groups. CONCLUSIONS: No main differences were found concerning the relief of pain between the two treatments. Diclofenac hydroxyethyl pyrrolidine may be the preferred choice because it is associated with less adverse reactions, together with a faster action in the relief of pain.

Different routes of progesterone administration and polycystic ovary syndrome: a review of the literature.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in woman of reproductive age. Although extensive studies have been performed in past decades to investigate the pathobiological mechanisms underlying the unset of this disease, its etiology remains unknown. Progesterone is a hormone of paramount importance in ovulation, implantation and luteal phase support. Low levels of progesterone have been found in the early luteal phase in PCOS patients. Granulosa cells from polycystic ovaries show an altered progesterone production. Moreover, the lack of cyclical exposure to progesterone may have a role in the development of the gonadotropin and androgen abnormalities found in PCOS patients. Ovulation failure and progesterone deficiency may facilitate the hypothalamic-pituitary abnormalities causing the associated disordered luteinizing hormone secretion in PCOS. Progesterone may be administered to PCOS patients in the following cases: to induce withdrawal bleeding, to suppress secretion of luteinizing hormone, in ovulation induction in clomiphene citrate-resistant patients and in luteal phase support in assisted reproduction. We discuss the pharmacologic characteristics of the different routes of progesterone administration with reference to these diverse indications, the therapeutic objectives and patient compliance.

Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness.

The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (218.51 +/- 88.69 versus 312.22 +/- 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 +/- 271.9 versus 589.1 +/- 244.7; P < 0.0001). The cost-effectiveness (i. e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU.

Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: a prospective, controlled, randomized trial.

OBJECTIVE: To compare the effectiveness of i.m. P and i.m. P plus oral phytoestrogens for luteal phase support in patients undergoing IVF-ET cycles. DESIGN: Prospective, controlled, randomized trial. SETTING: University Hospital, Perugia, Italy. PATIENT(S): Two hundred thirteen infertile patients undergoing IVF-ET were included in the study. The inclusion criteria were use of a GnRH agonist for pituitary down-regulation and age <40 years. The total number of cycles performed was 274. INTERVENTION(S): Patients were assigned to receive either i.m. P (50 mg daily) plus placebo or P (50 mg daily) plus phytoestrogen supplementation (1,500 mg daily) for luteal phase support starting from the evening of oocyte retrieval until either a serum pregnancy test result was negative or embryonic heartbeat was sonographically confirmed. MAIN OUTCOME MEASURE(S): The outcomes of IVF-ET were evaluated in both study groups in terms of implantation rate, biochemical pregnancy rate (PR), clinical PR, spontaneous abortion rate, and ongoing pregnancy/delivered rate. RESULT(S): Statistically significant higher values for implantation rate, clinical PR, and ongoing pregnancy/delivered rate were recorded in the patients who received P plus phytoestrogens for luteal phase support in comparison with patients receiving P and placebo. CONCLUSION(S): Although the results of this study encourage the use of phytoestrogens for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that phytoestrogens have a beneficial effect in IVF cycles.

Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness.

OBJECTIVE: To compare the clinical results and the cost effectiveness of urinary FSH and recombinant FSH in ovarian stimulation for IUI cycles. DESIGN: Prospective, randomized trial. SETTING: University Hospital, Perugia, and A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy. PATIENT(S): IUI cycles were performed in 67 infertile patients. INTERVENTION(S): Protocols of ovarian stimulation with urinary FSH or recombinant FSH were randomly assigned, for a total of 138 cycles performed (67 and 71, respectively). MAIN OUTCOME MEASURE(S): Number of mature follicles, days of stimulation, number of ampules, and IU used per cycle, biochemical/clinical pregnancy rates and cost-effectiveness ratio. RESULT(S): Follicular development, length of stimulation, pregnancy and delivery rates were not statistically different. Although in the urinary FSH group a significantly higher number of IU of gonadotropins were used (815.5 +/- 284.9 vs. 596.0 +/- 253.8), the cost per cycle remained significantly lower (220.73 +/- 94.72 vs. 318.50 +/- 125.21). The cost-effectiveness ratio was 1,848.61 euro in the urinary FSH group and 2,512.61 euro in the recombinant FSH group. CONCLUSION(S): Urinary FSH and recombinant FSH are both effective in ovarian stimulation in IUI cycles. The urinary preparation is more cost effective due to the difference of its cost per IU.

17 alpha-hydroxyprogesterone caproate versus intravaginal progesterone in IVF-embryo transfer cycles: a prospective randomized study.

One of the main issues in the management of IVF and embryo transfer techniques is to ensure adequate concentrations of progesterone. The aim of this prospective, randomized study was to compare the effectiveness of 17 alpha -hydroxyprogesterone caproate (17-HPC) administered intramuscularly and intra-vaginal progesterone in gel in luteal phase support in patients undergoing IVF-embryo transfer cycles. A total of 320 patients were randomly treated with either 17-HPC (341 mg i. m. every 3 days) or progesterone vaginal gel (90 mg daily). The inclusion criteria were the use of gonadotrophin-releasing hormone down-regulation and age <40 years. The outcome of IVF in both study groups was evaluated for implantation rate, biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rate. The results of this study showed that 17-HPC conferred more benefit to IVF-embryo transfer cycles compared with intra-vaginal progesterone, as demonstrated by the results of most of the main outcome parameters considered. The data showed that 17-HPC administered every 3 days appears to be more effective in providing luteal support in comparison to intra-vaginal progesterone.

Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy. PATIENT(S): Three hundred seventy-six postmenopausal healthy women, all with intact uterus. INTERVENTION(S): Women were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years. MAIN OUTCOME MEASURE(S): Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment. RESULT(S): Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%). CONCLUSION(S): Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.

High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.

OBJECTIVE: To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study. METHODS: A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. RESULTS: Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted. CONCLUSION: A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.