Effect of progesterone and its 5 alpha and 5 beta metabolites on symptoms of premenstrual syndrome according to route of administration. Investigation of the efficacy of progesterone pessaries in the relief of symptoms of premenstrual syndrome. progesterone Study Group. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles. Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy. Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. High-dose medroxyprogesterone acetate versus estramustine in therapy-resistant prostatic cancer: a randomised study. Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints. Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints.
Orally administered progesterone may have advantages over other routes of administration in the treatment of premenstrual syndrome (PMS) because of substantially higher levels of the anxiolytic metabolites 5 alpha and 5 beta pregnanolone. The only previous placebo-controlled trial which used oral progesterone reported beneficial effects in the treatment of PMS. The present study, a double-blind crossover trial, compared the administration of 300 mg daily oral progesterone with 200 mg daily vaginal progesterone and matched placebos for 10 days premenstrually. Although there was a significant treatment effect on symptoms, no difference between active treatments and placebo was found. The trial was terminated with 25 women completing treatment as it was evident that no clinically significant effect of either form of progesterone was likely to be detected even with twice the sample size. Serum levels of progesterone and metabolites showed that oral administration resulted in supraphysiological levels of 5 alpha and 5 beta metabolites and there was a negative correlation between 5 alpha pregnanolone levels and anxiety. However, this did not translate to overall reduction in premenstrual distress or anxiety beyond that achieved by placebo, as measured by validated questionnaires. A variety of definitions have been applied to premenstrual syndrome. The severity of the syndrome is also variable.
                A study was undertaken to compare progesterone pessaries with placebo in the relief of symptoms of premenstrual syndrome. In this study the condition was characterized by a wide range of symptoms recurring in the late luteal phase but absent in the follicular phase (that is, the specific definition published by Dalton in 1953).
                A multicentre, prospective, double-blind, randomized, parallel group study was undertaken by 45 general practitioners. Patients were deemed eligible after two prospective menstrual cycles of observation (selection phase) in which a precise definition of symptoms was applied. Patients were randomized to use either progesterone pessaries (400 mg twice a day) or matching placebo, by vaginal or rectal administration, from 14 days before the expected onset of menstruation until the onset of vaginal bleeding, for four consecutive cycles. Baseline data for the outcome variables were determined in the selection phase. The main outcome variables were changes in the severity (categorized as none, mild, moderate or severe) of each patient's most severe symptom, and in the average score of all the patient's symptoms characteristic of premenstrual syndrome. Spontaneous reports of adverse events were recorded.
                A total of 281 patients were screened for premenstrual syndrome; of these, 141 patients were randomized to treatment or placebo groups. Efficacy was evaluated in 93 patients. Reductions in the scores of the highest scoring, most severe, symptoms and in the average symptom score, were consistently observed in patients receiving progesterone pessaries and in those receiving placebo. The response to progesterone was greater than to placebo during each cycle; the differences were clinically and statistically significant. Adverse events were reported by 51% of patients in the progesterone treatment group and by 43% in the placebo group. Irregularity of menstruation, vaginal pruritus and headache were reported more frequently by patients taking active therapy.
                In this study, progesterone, given as pessaries by vaginal or rectal administration, was more effective than placebo in the relief of symptoms of premenstrual syndrome in a population of patients selected by strict entry criteria. To compare the efficacy of a vaginal progesterone preparation with our standard IM preparation within a donor egg program.
                Prospective randomized trial.
                Donor egg program at a university assisted reproductive therapy program (Jones Institute for Women's Health).
                Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve.
                Women were randomized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement. Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed. Subjects with residual ovarian function received a GnRH agonist. In the IM treatment group, 100 mg was administered from cycle days 15 to 27. In the vaginal treatment group, Crinone 8%, a polycarbophil-based gel preparation containing 90 mg of micronized progesterone, was administered twice daily from the evening of day 14.
                Endometrial histology, serum levels of progesterone (on days 13, 17, 20, 24, and 26), the occurrence of pregnancy, implantation rate, and pregnancy outcome.
                Fifty-four women randomized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET. Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group. Endometrial histology was "in phase" for all subjects in both groups. Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups, respectively. The ongoing pregnancy rate (PR) of 31% (17/54) and implantation rate of 23% in the subjects receiving Crinone was not statistically different from the IM progesterone group's ongoing PR of 22% (4/18) and implantation rate of 18%.
                Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered. To find out the effect of estradiol with progesterone for luteal phase support in IVF-ICSI cycles.
                Patients were accepted for treatment in the ART unit of Selcuk University, Meram Faculty of Medicine, between January 2001 and March 2003. The study was done in a prospective manner. The age range of 252 women was 19-41 years and the total number of cycles was 310. All patients were treated with a long ovulation induction protocol. Patients were treated and divided into two groups in a randomized manner: group I used only 600 mg/day divided into three equal doses of micronized progesterone vaginally, and group II used transdermal estradiol 100 microg/day + 600 mg/day vaginal micronized progesterone.
                310 ICSI cycles were carried out in 252 infertile couples between January 2001 and March 2003. From 22 of these cycles, oocytes were retrieved but no embryos were developed. In the remaining 288 cycles there were embryo transfers. All embryo development was achieved by ICSI treatment. In 148 out of 288 cycles, the luteal phase was supported only by vaginal micronized progesterone (group I). On the other hand, the remaining 140 cycles received vaginal micronized progesterone plus transdermal estradiol 100 microg/day (group II). The number of beta-hCG-positive results in group I and group II were 20 (13.5 %) and 54 (38.5%) respectively.
                Adding estradiol to progesterone for luteal phase support in ICSI-ET cycles may increase implantation and pregnancy rates.
                Copyright (c) 2004 S. Karger AG, Basel. In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) This study aimed to compare the efficacy of micronized progesterone administered as luteal support following ovulation induction for in-vitro fertilization (IVF)- embryo transfer in cycles using gonadotrophin-releasing hormone agonist, either orally (200 mgx4/day) or vaginally (100 mgx2/day) and to characterize the luteal phase hormonal profile during such treatments. A total of 64 high responder patients requiring intracytoplasmic sperm injection due to male factor infertility were prospectively randomized into two treatment groups. Patients treated orally or vaginally were comparable in age (31.9 +/- 6.1 versus 30.6 +/- 5.2; mean +/- SD), number of oocytes retrieved (17 +/- 8.2 versus 18 +/- 7.0), and number of embryos transferred (3.1 +/- 1.2 versus 2.7 +/- 0.9) per cycle. Following low dose vaginal treatment, a significantly higher implantation rate (30.7 versus 10.7%, P < 0.01), but similar clinical pregnancy rate (47.0 versus 33.3%) and ongoing pregnancy rate (41.1 versus 20.0%) was observed, compared with oral treatment. In conception cycles, luteal serum progesterone and oestrogen concentrations did not differ between the treatment groups. In non-conception cycles, late luteal progesterone concentrations were significantly lower following vaginal treatment. As low dose micronized progesterone administered vaginally is simple, easy and well tolerated, it could be recommended as the method of choice for luteal support, especially for high responder patients at risk for ovarian hyperstimulation syndrome. A series of 105 patients with metastatic prostatic cancer, having progressed on first-line hormonal treatment, were randomised to high-dose medroxyprogesterone acetate (MPA) 1000 mg i.m. daily for 15 days, followed by 1000 mg weekly (53 patients), or to estramustine 280 mg per os twice daily (52 patients). The treatment was discontinued because of side effects in 3 of 51 evaluable MPA-treated patients and in 8 of 51 evaluable estramustine-treated patients. Progression-free survival was short in both groups and no statistically significant difference between them was observed. After 1 year, 70% of the patients had died and there was no statistically significant difference between the 2 treatments in the cumulative observed survival rates. According to modified SPCG criteria, remissions lasting from 12 to 56 weeks were noted in 13 MPA-treated patients and in 4 estramustine-treated patients. This difference was statistically significant. After cross-over, 6 of 33 patients in the MPA group had a remission compared with 1 of 24 in the estramustine group. It was concluded that the response rate, considering both subjective and objective response criteria, was better with MPA and the side effects were fewer. Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens. All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol-17 beta in combination with either norethisterone acetate 1 mg (group A) or 0.5 mg (group B) or megestrol acetate 5 mg (group C) or 2.5 mg (group D). The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A. The endometrium was atrophied in nearly all biopsies. Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate. It is concluded that a continuous oestradiol-progestogen combination can be used for long-term treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered. Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron, 2 x 5 mg daily for 12 days each month).
                One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months.
                With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group.
                Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.
The trials did not show that progesterone is an effective treatment for PMS nor that it is not. Neither trial distinguished a subgroup of women who benefited, nor examined claimed success with high doses.