Use Of Progestagens Research Articles

The potential of biodegradable polymers: Chitosan, polyethylene glycol, and polycaprolactone as materials for progesterone intravaginal devices

<p><span lang="EN-US">For several decades, a protocol based on the use of progestagens has been used to manage livestock reproduction with minimal alterations. Recently, researchers have gained insight into the short-term use of progestagen protocols lasting 5-7 days, which has been found to reduce the incidence of vaginitis and obviate the use of antibiotics. Additionally, this approach enables the reutilization of silicone-based devices such as CIDRs after a thorough biosecurity assessment. However, these devices have certain limitations. At the end of the treatment, they must be disposed of and cannot be reused, necessitating a re-evaluation of their use for technical and societal reasons, including animal health and welfare, food safety, and environmental impact.</span><span lang="EN-US">A chitosan-PEG intravaginal implant formulation released progesterone for a period of four days, corresponding to the degradation time of the implant in the vagina. The use of a simple melting and molding process for the combination of PCL-PEG-chitosan implants has been observed to result in degradation of both simulated vaginal fluid and vaginal tissue of cows. The development of intravaginal devices made from biodegradable polymers is considered a potential solution because these materials would degrade within the body, eliminating the need for removal and leaving no residue. These devices are safe for animals and the environment.</span></p>

The Relationship between the Prevalence of Cesarean Sections and Progesterone (Duphaston) Usage during Pregnancy

Background: Progesterone plays a crucial part in ovulation, implantation, and pregnancy, among other reproductive processes.This is related to progesterone's role in controlling cyclical changes in decidualization and proliferation, which regulate uterine function during the menstrual cycle. Progesterone is necessary for the development of decidual tissues. In the event of fertilization, high levels of progesterone in the blood are crucial for maintaining pregnancy by promoting uterine growth and inhibiting the effects of factors that cause myometrial contraction. During a cesarean section, the fetus is delivered via a surgical incision made in the woman's abdomen (laparotomy) and in her uterus (hysterotomy). The likelihood of experiencing health issues following a cesarean birth is somewhat increased due to the high number of caesarean sections performed globally in comparison to spontaneous births. Method: 65 pregnant women participated in this cross-sectional study, which ran from October 1, 2022, to March 20, 2023, in the gynecological department of Salah Al Deen General Hospital in the Salah al Deen governorate and in Diyala. Result: As in result of questioners in pregnancies take the progesterone as stabilizer About 75.4% of participants were delivered by cesarean section and only 24.6% were delivered by normal vaginal delivery . Conclusion: The regular use of progestagens for the treatment of impending miscarriage may have contributed to the increased rate of cesarean sections among the participants.

Use of progestagens to preserve pregnancy: modern approaches

Review objectives: to summarize current and clinical data on the role of progesterone support in women at risk of miscarriage and premature pregnancy according to the standards of evidence-based medicine. Control of plasma progesterone levels is a fundamental tool for managing the effectiveness of assisted reproductive technologies. The association of a low level of serum progesterone with lower rates of current pregnancy and live birth in cycles of assisted reproductive technologies was revealed. Patients with low serum progesterone on the day of embryo transfer need individualized support of the luteal phase, which involves adding additional doses of progesterone to standard regimens.
 Vaginal micronized progesterone is currently believed to be the only progestogen that increases the likelihood of a live birth in women with bleeding in early pregnancy which has one or more miscarriages.
 Vaginal progesterone can be considered for patients with a high risk of miscarriage in the following modes: with vaginal bleeding and a history of one or more miscarriages (threatened miscarriage) – 400 mg twice a day, starting with the detection of vaginal bleeding up to 16 full weeks of pregnancy; with a history of three or more pregnancy losses of unknown etiology (habitual miscarriage) – asymptomatic patients — 200 mg twice a day up to 12 full weeks of pregnancy; patients with vaginal bleeding – 400 mg 2 times a day up to 16 weeks of pregnancy. Currently, there is no evidence of the effectiveness other forms of progesterone and other doses.
 Conclusions. Vaginal micronized progesterone demonstrated: high efficiency as a standard of luteal phase support; increasing the chance of a live birth in women with a double risk factor for miscarriage (vaginal bleeding in the 1st trimester and ≥1 previous miscarriage); the absence of safety problems for the fetus and the health of newborns when used in the early and late stages of pregnancy.

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

SummaryBackgroundPublished findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.MethodsPrincipal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.FindingsDuring prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.InterpretationIf these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.FundingCancer Research UK and the Medical Research Council.

Hormonal protocols for early resynchronization of ovulation in ewes: The use of progestagens, eCG, and inclusion of early pregnancy diagnosis with color Doppler ultrasound

This study aimed to evaluate 1) the effect of inserting an intravaginal sponge containing medroxyprogesterone during the late luteal phase on the corpus luteum (CL) function and endogenous production of P4; 2) the effectiveness of two different equine chorionic gonadotrophin (eCG) doses on synchronization of ovulations for a resynchronization treatment; and 3) the inclusion of an early pregnancy diagnosis in an early resynchronization protocol for ovulation in ewes. For all studies, the synchronization protocol was based on a short-term protocol of six days of progestogen treatment plus one dose of prostaglandin F2alpha, one dose of eCG, and gonadorelin acetate after sponge withdrawal. For the first study, the ewes were mated with fertile rams; a second sponge was inserted in half of these ewes 12 days later, and blood samples were collected daily for six days, until sponge withdrawal. For the second study, the ewes were not mated, and received a second sponge during the same period, after which they were divided into three groups according to eCG dose (0, 200, or 300 IU). In the third study, all ewes were artificially inseminated and received the second sponge during the same period. At sponge withdrawal, pregnancy was diagnosed by color Doppler ultrasonography (DUS) of the CL, and only non-pregnant ewes were re-inseminated two days later. In the first study, serum progesterone values were similar regardless of whether an intravaginal sponge had been inserted. In the second study, the ovulation time was more concentrated in those ewes which received 200 IU of eCG. In the third study, there was no difference between the experimental groups (with or without a previous pregnancy diagnosis) in pregnancy rate at the first insemination, accumulated pregnancy rate, and pregnancy loss. The insertion of an intravaginal sponge impregnated with medroxyprogesterone acetate did not affect the endogenous production of P4. The application of 200 IU of eCG provided the best result with regard to the synchronization of ovulations in the resynchronization treatment. Also, the inclusion of an early pregnancy diagnosis with DUS is useful and improves the general results of resynchronization programs, shortening the total working period.

What can I give to calm this stallion down?

What can <scp>I</scp> give to calm this stallion down?

Preovulatory progestagen treatment in mares fails to delay ovulation

The major objective of this study was to determine whether short-term preovulatory progestagen treatment of mares could effectively delay ovulation. Secondary objectives were to determine the effect such supplementation had on signs of estrus, follicular growth, postovulatory luteal function and pregnancy rate. Thirteen cyclic mares of different breeds were used in this study during the natural breeding season. Once mares were confirmed in estrus with a follicle of 35mm in diameter, they were assigned in random order to receive no treatment (control), placement of a progesterone-impregnated controlled intravaginal drug releasing device (CIDR) for 2days, or oral altrenogest treatment (0.044mg/kg/d) for 2days. Transrectal ultrasonography and teasing with a vigorous stallion were performed daily. Mares were inseminated every 48h after the end of experimental treatment (progestagen groups) or beginning when the follicular diameter was 35mm (control group) with fresh extended semen of a single fertile stallion. Each mare was followed for 3–5 cycles, allowing each treatment to be applied one or two times.Neither CIDR nor altrenogest treatment delayed ovulation. Treatment had no effect on follicular growth rate or the size of the ovulatory follicle immediately preceding ovulation. Both forms of progestagen treatment effectively abolished estrous behavior within 24h. Estrous response to the stallion returned to the control level after cessation of treatment. Similarly, a reduction in endometrial edema was detected during progestagen treatment, which returned to normal after cessation of treatment. Altrenogest treatment tended to reduce the chance of pregnancy (P=0.09) compared to the control group. The use of progestagens to delay ovulation in mares lacks efficacy and may threaten successful establishment of pregnancy.

Progestagens and anti-progestagens for pain associated with endometriosis

Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices. To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis. We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011. We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis. We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself. The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006). There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.

Caractéristiques et déterminants de l’initiation d’un traitement progestatif oral dans la cohorte française E3N

To describe the characteristics and determinants of initiation of use of progestagens alone - i.e. without concomitant use of estrogen - among French premenopausal women. Forty-one thousand six hundred and three women from the French E3N cohort were included in our analyses. Prevalence of use was calculated from 1992 to 2005. Determinants of progestagens alone initiation were investigated prospectively from 1992 to 2005, using multivariable Cox proportional hazards models. Fifty-eight per cent of women who had reached menopause between 1992 and 2005 ever used progestagens alone during their premenopause. Between 1992 and the end of 1990s, the increase in the prevalence of progestagens alone use in our cohort was close to 50%. Initiation of progestagens alone was significantly associated with a high level of education (postgraduate compared to high-school graduate: Hazard ratio [HR]: 1.09 95% confidence interval [CI]: 1.01-1.18), with a normal body mass index (overweight and obese women compared to normal-weight women: HR=0.84, 95% CI: 0.79-0.90 and HR=0.79, 95% CI: 0.69-0.89 respectively), history of gynecological disorders (mastalgia, benign breast disease and benign uterine or ovarian disease [HR=1.38, 95% CI: 1.27-1.49, HR=1.18, 95% CI: 1.13-1.24 and HR=1.60, 95% CI: 1.52-1.68 respectively]) and with recent gynaecological screening (as measured by recently performed mammogram or Pap smear HR=1.11, 95% CI: 1.05-1.17 and HR=1.38, 95% CI: 1.27-1.49 respectively). Since, at least in France, use of progestagens alone at premenopause is common, evaluation of its risks and benefits is of public health importance.

215 DELETERIOUS EFFECTS OF PROGESTAGEN TREATMENT ON FUNCTIONALITY OF PREOVULATORY FOLLICLES IN SHEEP

The use of progestagen for 14 days in protocols for estrus synchronization has been reported to affect conception rate in sheep. We evaluated the effects of progestagen treatment on the growth pattern and follicular function of preovulatory follicles (PF) and their implication for subordinated follicles (SF). Adult female sheep were randomly assigned to the following estrus synchronization groups: 1) FGA (n = 7), which received an intravaginal device of fluorogestone acetate sponges (Chronogest®, Intervet International, Boxmeer, the Netherlands) for 14 days, or 2) PGF (n = 7), which received 3 i.m. administrations of 125 μg of cloprostenol (Estrumate®, Mallinckrodt Vet GmbH, Friesoythe, Germany) 10 days apart. The third cloprostenol administration in the PGF group was given at the same time of sponge withdrawal in the FGA group (Day 0 = day of sponge withdrawal). Ultrasonographic examinations of the ovaries for assessment of follicular development were carried out daily from Days 0 to 2 by using a scanner (Aloka SSD500) equipped with a 7.5-MHz transducer adapted for transrectal examinations. Follicular function was evaluated in terms of estradiol secretion, and blood samples were taken every 12 h to determine plasma estradiol concentration from Days 0 to 2. Ovaries from all females in both groups were recovered by ovariectomy on Day 2 to determine apoptosis by immunohistochemistry for active caspase-3 in granulosa cells from SF of 3 to 5 mm in diameter. Additionally, SF were histologically classified as healthy, early, or advanced atretic. Data were analyzed by Student t-test and Pearson correlation. The total number of PF observed on Day 2 was 15 and 12 for the PGF and FGA groups, respectively. The 90.9 and 93.3% of PF recorded in the PGF and FGA groups, respectively, on Day 2 was retrospectively identified on Day 0. The 33.6 and 46.6% of those follicles from the PGF and FGA groups, respectively, corresponded to follicles &gt;5 mm in diameter. Although mean diameter of PF was higher in the FGA group than in the PGF group (5.4 ± 0.4 mm v. 4.5 ± 0.4 mm, respectively; P &lt; 0.01) on Day 0, PF diameter was similar between groups on Day 2. Plasma estradiol concentration was significantly higher (P &lt; 0.05) in the PGF group on Day 1 (3.1 ± 0.2 pg/mL v. 1.7 ± 0.2 pg/mL in the FGA group) but did not differ between groups on Day 2. The growing pattern of the PF in the PGF group significantly (P &lt; 0.05) affected the total number of SF, and there was a tendency (P = 0.08) for an increase of the total number of healthy follicles in the same group. In addition, advanced atretic follicles from the FGA group were significantly higher than those observed in the PGF group (P &lt; 0.001). Additionally, caspase-3 immunoreactivity was higher in the FGA group than in the PGF group (P &lt; 0.05) and it was associated with the largest SF in both groups. All of these finding are indicative of the presence of aged follicles with an extended permanence in the ovary. We concluded that the use of progestagen for 14 days in protocols for estrus synchronization in sheep affects the growth pattern and functionality of the preovulatory follicle during the follicular phase and may have a deleterious consequence on oocyte competence. CYCITAGL2005-02669 and DID-D-2007-03 UACh.

Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder

The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy. Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary outcome measure was daily symptom ratings for mood and physical symptoms. The highest dose of estradiol in combination with progesterone was associated with the most pronounced symptom recurrence, both in comparison with a lower dose of estradiol together with progesterone and estradiol-only treatment. Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.

The use of progesterone and other progestational agents to prevent spontaneous preterm labour and preterm birth

Background: Preterm birth is the major cause of perinatal mortality and morbidity in the developed world, making a huge impact on healthcare costs. There is accumulating evidence that the prophylactic use of progestagens is able to reduce significantly the incidence of low birth weight and preterm birth. Objectives: to emphasise the importance of preterm birth; to review the role of progesterone in inducing myometrial quiescence which prevent preterm labour and preterm birth; to review the published literature and planned future research on the use of progestagens for the prevention of preterm birth. Methods: A review of the published literature using accepted search engines. Results/conclusions: Progestagens have been demonstrated to reduce the incidence of low birth weight and preterm birth. Many questions remain unanswered, particularly the long-term safety concerns and also whether the use of progestagens results in improved neonatal and childhood outcomes.

Progestagens Use Before Menopause and Breast Cancer Risk According to Histology and Hormone Receptors

In a previous study, we found a positive association between premenopausal use of progestagens and breast cancer risk. We conducted the present study to assess the risk of breast cancers defined by their histology and hormone receptors status. We evaluated the association between progestagen-only intake (except for mini pills) before menopause and after the age of 40 years and invasive breast cancer risk in 67,057 women participating in the French E3N cohort study. Histologically confirmed invasive breast cancers (2,264) were identified through biennial self-administered questionnaires completed from 1992 to 2002. Risk estimates were calculated using the Cox proportional hazard model. We found an increased risk of lobular carcinoma associated with premenopausal use of progestagens among both current and past users [hazard ratio (HR), 1.51; 95% confidence interval (95% CI), 1.02-2.24 and HR, 1.38; 95% CI, 1.08-1.75, respectively]. Among current users, the use of progestagens for 4.5 years or more was associated with an increased risk of estrogen receptor-positive/progesterone receptor-positive carcinomas (HR, 1.68; 95% CI, 1.05-2.68), whereas current use of progestagens for <4.5 years was associated with an increase in the estrogen receptor-positive/progesterone receptor-negative carcinoma risk (HR, 1.61; 95% CI, 1.05-2.46). The premenopausal use of progestagens after the age of 40 years may be preferentially associated with the risk of lobular breast cancer and differentially affect the risk of breast cancer according to the hormone receptor status.

Oral progestagens before menopause and breast cancer risk

We examined the relationship between use of progestagen-only before menopause (except for mini-pills) after the age of 40 and invasive breast cancer risk in 73 664 women from the French E3N cohort study (mean age at start of follow-up, 51.8 years; mean duration of follow-up, 9.1 years). A total of 2390 cases of invasive breast cancer were diagnosed during follow-up. Risk estimates were calculated using the Cox proportional hazard model. Overall, ever use of progestagen before menopause was not significantly associated with risk (relative risk (RR): 1.01, 95% confidence interval: 0.93–1.11). However, we observed a significant increase in risk associated with the duration of use (P-value for trend: 0.012), current use of progestagens for longer than 4.5 years being significantly associated with risk (RR: 1.44, 95% confidence interval: 1.03–2.00). Prolonged use of progestagens after the age of 40 may be associated with an increased risk of breast cancer and the subject needs to be investigated further.

Progesterone/Progestagens to Prevent Preterm Birth: When and How

Prematurity is a leading cause of neonatal morbidity and mortality, accounting for most part of the deaths of infants without congenital anomalies. Also, the cost of neonatal intensive care and long-term care for infants born preterm is enormous. The medical, psychological, and economic burdens of preterm births are very important. In spite of advances in obstetrical care, the rate of preterm delivery in industrialized countries (approximately 10%) has not decreased over the past 40 years. In fact, it has increased slightly, partly due to the use of assisted reproductive technologies and to the rise of indicated preterm deliveries for maternal or fetal reasons Progesterone (P) is the primary factor of uterine quiescence that permits the physical distension of the uterine muscle throughout pregnancy. In all species, except humans, a drop in P levels precedes labor, whereas P levels remain constant in humans until delivery. Yet the labor inducing properties of anti P products such as RU-486 have led to hypothesize a functional P withdrawal prior to labor in humans. In spite of early trials suggesting a benefit with progesterone/ progestagens in preventing premature labor, the doubts in its efficacy, particularly linked to the very weak concentrations of exogenous administration compared to the high levels of endogenous P, have dissuaded its use in obstetrics for some years. Two recent studies, however, give a new momentum towards the use of progestagens for the prevention of premature delivery in a particular high-risk population: women with a prior preterm birth. Nevertheless, the use of progestagens in other populations at risk for preterm delivery should not be encouraged outside of clinical trials. In this review article we will discuss the indications for progesterone for prevention of preterm delivery, as well as the formulations to use.

Effects of progestagens and prostaglandin analogues on ovarian function and embryo viability in sheep

Current study assessed differences in the response of sheep to estrus synchronization either by the administration of two doses of prostaglandin or by the insertion of an intravaginal progestagen sponge. The preovulatory follicular dynamics and estradiol secretion, the ovulatory response and progesterone secretion and the number and quality of embryos were studied in 27 ewes treated with two doses of 100 μg of cloprostenol, 10 days apart, and in 29 sheep treated with progestagen sponges for 14 days. Percentage of sheep responding to the synchronization treatments with signs of estrus behaviour was similar between both groups (81.5% versus 72.4%, respectively). The use of progestagen resulted in a higher diameter of the largest follicle (6.6 ± 0.2 versus 5.9 ± 0.2, P < 0.05), and a lower number of small (6.7 ± 0.3 versus 9.6 ± 0.4, P < 0.005) and total follicles (10.3 ± 0.3 versus 12.9 ± 0.4, P < 0.005). However, mean plasma estradiol concentration during the follicular phase was higher in cloprostenol treated sheep ( P < 0.005). The mean ovulation rate was similar in both treatments (1.7 ± 0.2 versus 1.7 ± 0.3), but progesterone concentration during the early luteal phase was again higher in sheep treated with cloprostenol ( P < 0.05). The mean number of retrieved oocytes/embryos was very similar in both treatments (1.2 ± 0.2 versus 1.4 ± 0.2) and showed similar fertilization rates (70.6% versus 66.7%), but, although differences did not reach statistical significance, final viability rate was higher in cloprostenol than in progestagen treated ewes (58.9% versus 46.1%, P = 0.07). Current results give new evidences supporting the negative effects of progestagens on the functionality of ovulatory follicles and support the development of new protocols for assisted reproduction including the use of prostaglandin analogues.

In this issue

In this issue

A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer

Objective The goal of this study was to determine response rate and evaluate toxicity of LY353381 (arzoxifene) in patients with recurrent or advanced endometrial cancer (EC). Methods A phase II, open-labeled study with arzoxifene was performed at 13 centers. Patients with measurable recurrent/advanced EC not amenable to curative therapies were eligible if either the primary tumor or recurrent tumor was ER+ and/or PR+. If receptor status could not be determined, patients with well or moderately well-differentiated EC were also permitted. Prior use of salvage chemotherapy was not allowed; however, prior use of progestagens was permitted and patients were stratified by prior exposure to progestagen. Patients received 20 mg/day PO, and were treated for at least 8 weeks in the absence of disease progression or unacceptable toxicity. Efficacy was based on the frequency of complete (CR) and partial (PR) responses, and a 95% confidence interval (CI) was calculated. The Kaplan–Meier method was used to analyze time to progression and duration of response. Results From February 1999 through April 2001, 37 patients were entered of whom 34 received treatment. Efficacy was evaluated for the 29 patients who received at least 4 weeks of therapy and at least one tumor response assessment. Safety was assessed in all 34 patients who received any drug. Thirty patients were defined as progestagen sensitive, and 4 patients were defined as progestagen failures. Twenty-six patients were ER+, and 22 were PR+. Nine (1 CR + 8 PR) of 29 patients responded (31%, CI 25–51%), with a median duration of response of 13.9 months. All 9 responses occurred in progestagen-sensitive patients. Two additional patients (one from each progestagen cohort) had stable disease for ≥6 months. The median progression-free interval was 3.7 months (CI 1.9–6.6 months) for all 29 patients. Toxicity was minimal with no grade 3–4 toxic effects, and 9 patients had only grade 1–2 toxic effects (7 grade 1, 2 grade 2). Hot flashes were the most common toxic effect and, in all 3 reported cases, were grade 1. Conclusions Arzoxifene has demonstrated a high response rate with the longest median duration of response reported in a phase II trial of this patient population. The ease of administration and extremely favorable toxicity profile make this an agent warranting further evaluation.

The importance of osmotic pressure for the quality of fresh, cooled, and cryopreserved equine spermatozoa

The major objective of this study was to determine whether short-term preovulatory progestagen treatment of mares could effectively delay ovulation. Secondary objectives were to determine the effect such supplementation had on signs of estrus, follicular growth, postovulatory luteal function and pregnancy rate. Thirteen cyclic mares of different breeds were used in this study during the natural breeding season. Once mares were confirmed in estrus with a follicle of 35 mm in diameter, they were assigned in random order to receive no treatment (control), placement of a progesterone-impregnated controlled intravaginal drug releasing device (CIDR) for 2 days, or oral altrenogest treatment (0.044 mg/kg/d) for 2 days. Transrectal ultrasonography and teasing with a vigorous stallion were performed daily. Mares were inseminated every 48 h after the end of experimental treatment (progestagen groups) or beginning when the follicular diameter was 35 mm (control group) with fresh extended semen of a single fertile stallion. Each mare was followed for 3–5 cycles, allowing each treatment to be applied one or two times.Neither CIDR nor altrenogest treatment delayed ovulation. Treatment had no effect on follicular growth rate or the size of the ovulatory follicle immediately preceding ovulation. Both forms of progestagen treatment effectively abolished estrous behavior within 24 h. Estrous response to the stallion returned to the control level after cessation of treatment. Similarly, a reduction in endometrial edema was detected during progestagen treatment, which returned to normal after cessation of treatment. Altrenogest treatment tended to reduce the chance of pregnancy (P = 0.09) compared to the control group. The use of progestagens to delay ovulation in mares lacks efficacy and may threaten successful establishment of pregnancy.

Progestagen reduces cancer risk in HRT.

Progestagen use for ten or more days per cycle can reduce the excess risk of endometrial cancer associated with longterm postmenopausal oestrogen use.