Normal Progesterone Levels Research Articles

O-147 Role of serum progesterone levels and subcutaneous progesterone supplementation in endometriosis patients undergoing artificial cycle frozen embryo transfer

Abstract Study question Is there any impact of serum progesterone levels and subcutaneous progesterone supplementation on live birth rate in endometriosis patients undergoing Artificial Cycle-Frozen Embryo Transfer (AC-FET)? Summary answer Endometriosis patients have comparable progesterone levels before transfer to those without endometriosis. Progesterone supplementation results in similar live birth rate (LBR) to the general population. What is known already Progesterone (P4) resistance is a hallmark of uterine alterations in endometriosis. This disease could disrupt balance between progesterone and estrogen signaling pathways, resulting in estrogen dominance and progesterone resistance at the receptor level, which warrants a deeper exploration for adjusting dosages when performing AC-FET. A recent retrospective study highlights the potential significance of a progesterone threshold when using vaginal and intramuscular progesterone systematically in AC-FET, correlating with a significantly higher LBR for endometriosis-patients. However, no current studies have compared LBR according to P4 the day before blastocyst-transfer and progesterone supplementation in endometriosis versus non-endometriosis-patients undergoing AC-FET with standard vaginal treatment. Study design, size, duration This is a retrospective cohort study including 985 cycles undergoing autologous AC-FET with standard vaginal progesterone treatment (600 mg/day) at a university-affiliated fertility center from January 2019 to December 2022. 168 cycles were from patients with confirmed endometriosis. LBR was evaluated in both groups based on P4 levels the day before transfer. Progesterone supplementation via SC injection (25 mg/day) was administered when levels were deemed low (<10.6 ng/mL based on our previously published research). Participants/materials, setting, methods Endometrial preparation involved oral estrogens at 6 mg daily from the begging of menstrual cycle. Micronized vaginal progesterone (600 mg/day) was added when thickness reached 7 mm. P4 was measured before embryo transfer; supplementation (25 mg SC injection) was added if < 10.6 ng/mL. FET occurred 6 days after initiating luteal phase support. Treatment continued until the pregnancy test. If pregnant, treatment ceased at 10 weeks of amenorrhea. Main results and the role of chance Comparisons between endometriosis and non-endometriosis groups revealed similar baseline characteristics regarding age, BMI, parity, number of embryos transferred, and embryo quality. The number of cycles with levels ≥10.6 ng/mL before transfer were comparable between patients with and without endometriosis (aOR 0.98, 95% CI 0.65-1.47) according to a multivariable logistic regression analysis adjusting for age, BMI, and prior progesterone levels <10.6ng/mL the day before transfer. Unadjusted findings demonstrated equivalent clinical pregnancy, miscarriage, and live birth rates in endometriosis compared to non-endometriosis patients. A subsequent multivariable logistic regression analysis to analyze LBR was conducted, considering four groups: Group 1: Endometriosis with progesterone <10.6ng/mL and SC supplementation (51 patients) Group 2: Endometriosis with progesterone ≥10.6ng/mL (117 patients) Group 3: Non-endometriosis with progesterone <10.6ng/mL and SC supplementation (274 patients) Group 4: Non-endometriosis with progesterone ≥10.6ng/mL (543 patients) Adjusted for age, BMI, and embryo quality, Group 1 was considered as the reference. Results showed comparable live birth rates between the reference group and Group 2 (aOR 0.79, 95% CI 0.36-1.74), Group 3 (aOR 0.91, 95% CI 0.45-1.8), and Group 4 (aOR 1.9, 95% CI 0.71-2.74). Subcutaneous supplementation for endometriosis patients with P4<10.6ng/mL the day before embryo transfer led to similar LBR compared to the other groups. Limitations, reasons for caution The main limitation of this study is the single-center retrospective approach. While the total number of endometriosis patients is 168, the representation of endometriosis patients in group 1 may be a study limitation. Furthermore, all endometriosis stages were analyzed together although this may be clinically distinct entities. Wider implications of the findings Endometriosis patients have the same risk to have P4<10.6ng/mL the day before FET as non-endometriosis patients. Vaginal progesterone, with subcutaneous supplementation if necessary, appears user-friendly, leading to a comparable live birth rate to that of patients with normal progesterone levels before transfer, regardless of endometriosis status. Trial registration number not applicable

Effect of slightly elevated progesterone on hCG trigger day on clinical pregnancy rate in GnRH-ant IVF/ICSI cycles

BackgroundIt was been agreed that significantly elevated progesterone level on the hCG trigger day have detrimental effect on clinical outcomes in IVF/ICSI cycles. However, few studies explored whether slightly elevated progesterone level also same impact on clinical outcomes.MethodsWe retrospectively studies the effect of slightly elevated progesterone level on outcomes of IVF/ICSI in GnRH-ant cycles. Propensity score matching was used to confounding variables. The women were divided into two groups according to the progesterone level: Group 1: < 1.0 ng/ml; Group 2: 1.0 ng/ml–1.5 ng/ml. Then compare the clinical pregnancy rate (CPR) between the two groups.ResultA total of 847 IVF/ICSI cycles were included in the present study. The average CPR per transfer cycle was 51.7%. CPR of group 1 was 55.22%, significantly higher than that of group 2 (40.66%, P = 0.013). Progesterone level on the day of hCG injection was further evaluated at threshold increments of 0.1 ng/ml, and the CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml.ConclusionThe slight elevation progesterone level on the hCG trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended.SummaryThe present retrospective study aimed to evaluate the effect of slightly elevated progesterone (1.0 ng/ml ~ 1.5 ng/ml) on outcomes of IVF/ICSI in GnRH-ant cycles. Slightly elevated progesterone level leaded to significant lower clinical pregnancy rate (CPR) that that of group with normal progesterone level (40.66% vs. 55.22%, P = 0.013). The CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml. So slightly elevated progesterone level on the trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended.

The effect of hormone therapy on the condition of the mammary glands in women with menstrual disorders of endocrine origin

The objective: to study the effect of stimulating hormone therapy on the condition of the mammary glands depending on the initial endocrine status of women with menstrual disorders in the background and after ovulation stimulation.Materials and methods. The study selected a group of 130 patients (n=130) of reproductive age (mean age 27±2,3 years), which by the nature of menstrual disorders are divided into 2 subgroups: 1 subgroup (n=57) – women with regular menstrual rhythm and insufficiency of the luteal phase (ILP), 2 subgroup (n=73) – women with secondary amenorrhea and oligomenorrhea on the background of chronic anovulation. All patients complained of no pregnancy for an average of 4±1,2 years. After a comprehensive assessment of the reproductive system and hormone-dependent organs, women received the proposed treatment with estrogen-progestogen drug, bromocriptine and ovulation stimulation with clomifene citrate.Results. During the preparatory (diagnostic) phase of the study it was found that in 1 subgroup in 89,5% of patients with concomitant diseases of the pelvic organs and only endocrine disorders of the ILP type in 10,5%. In women of 2 subgroup, the frequency of combined pathology was 23,3%, and endocrine disorders – 76,7%. These results confirmed the need for laparoscopic and hysteroscopic examination of all patients with infertility in addressing the issue of ovulation stimulation. After short cycles (3 months) of monophasic estrogen-progestogen therapy, 31,6% of patients with ILP and 17,1% with anovulation had a positive effect on reducing the incidence of pain in the mammary glands, with the most sensitive to therapy were patients with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components. When resuming biphasic ovulatory cycles with clomifene citrate stimulation, only 5,7% of women complained of breast pain during the first 1–2 cycles. No additional foci in the subgroups were detected, and previously diagnosed fibroadenomas did not increase.Conclusion. Analyzing the obtained data, a positive effect of different types of hormone therapy on the condition of the mammary glands in patients with menstrual and reproductive dysfunction, in particular with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components, is structures most sensitive to normal progesterone levels. Despite the lack of negative dynamics on the background of ovulation stimulation and restoration of normal mammary gland structure after therapy in women with menstrual disorders of endocrine origin, menstrual cycle regulation and dynamic monitoring of the mammary glands are shown to prevent the development of hyperplastic processes.

Luteal Phase in Assisted Reproductive Technology.

Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment of pregnancy. During the LP, the corpus luteum (CL) secretes progesterone and some other hormones that are essential to prepare the uterus for implantation and further development of the embryo, the function known as uterine receptivity. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, but also in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. LPD is particularly frequent in treatments using assisted reproductive technology (ART). Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. Altogether, these treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL. In addition to problems of endometrial receptivity for embryos, LPD also leads to dysfunction of the local uterine immune system, with an increased risk of embryo rejection, abnormally high uterine contractility, and restriction of uterine blood flow. There are two alternatives of LPD prevention: a direct administration of exogenous progesterone to restore the physiological progesterone serum concentration independently of the CL function, on the one hand, and treatments aimed to stimulate the CL activity so as to increase endogenous progesterone production, on the other hand. In case of pregnancy, some kind of LP support is often needed until the luteal–placental shift occurs. If LPD is caused by defective response of the endometrium and uterine immune cells to normal concentrations of progesterone, a still poorly defined condition, symptomatic treatments are the only available solution currently available.

Association of hepatitis E seropositivity and altered progesterone levels in pregnant women of low socioeconomic status from capital region of Pakistan.

To investigate the seroprevalence of hepatitis E virus infection, risk factors and its association with progesterone levels in pregnant women from low socioeconomic background. The cross-sectional study was conducted in Rawalpindi and Islamabad, Pakistan, from January to July 2012, and comprised pregnant asymptomatic healthy females from different clinics and hospitals of the twin cities. Data was collected using a predesigned demographic questionnaire to determine socioeconomic status. Prevalence of anti-hepatitis E virus antibodies and progesterone levels were determined using enzyme-linked immunosorbent assay kits. Of the 90 women, 35(39%) were in the 21-25 year age group, and 55(61%) belonged to low socioeconomic background. The overall prevalence of seropositive hepatitis E virus immunoglobulin-G was 54(60%) and immunoglobulin-M was 12(13.3%). In the first trimester, the levels of progesterone were higher in patients positive for immunoglobulin-M compared to immunoglobulin-G (p<0.001). Low socioeconomic status appeared to be a potential risk factor associated with high hepatitis E virus seroprevalence and alterations in the normal progesterone levels during pregnancy.

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.

The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

Correlation analysis of serum progesterone with clinical indicators and common traditional Chinese medicine syndrome types in male type 2 diabetic patients

To analyze the correlation of serum progesterone (PROG) level with blood biochemical parameters and common traditional Chinese medicine (TCM) syndromes in male patients with type 2 diabetes mellitus (T2DM). We collected the clinical data of 192 male patients with T2DM, who were admitted in the Department of Endocrinology, Nanjing Hospital of Chinese Medical Affiliated to Nanjing University of Chinese Medicine between January, 2018 and March, 2019. The general clinical data, C-peptide level, blood glucose level, glycated hemoglobin (HbA1c), HOMA, blood lipid level, and sex hormones were compared between the patients with normal PROG and elevated PROG levels and also between the patients with two common TCM syndromes, namely qi and Yin deficiency syndrome and damp- heat accumulation in the spleen syndrome. We further compared the sex hormones, C-peptide level, HOMA, HbA1c, and blood glucose level among the patients with the two TCM syndromes having normal or elevated PROG levels. Compared with those in patients with normal PROG level, BMI, C-peptide, HOMA-β, and HOMA2-IR were significantly lowered and HOMA-IS, E2, and T were significantly increased in patients with elevated PROG level; no statistical differences were found in age, disease duration, waist-to-hip ratio (WHR), smoking history, blood pressure, blood glucose, blood lipids, HbA1c, LH, FSH or PRL between the two groups. Compared with the patients with damp-heat accumulation syndrome group, the patients with qi and Yin deficiency syndrome were older and had a longer disease duration, a greater BMI, and higher levels of PROG, C-Peptide, HOMA-β, HOMA2-IR and HOMA-IS, but the smoking history, WHR, HbA1c, blood glucose, and sex hormone levels were comparable between the two groups. Among the 4 groups of patients with different PROG levels and TCM syndromes, significant differences were found in the levels of C-peptide, HOMA-β, HOMA-IS, HOMA2-IR, PROG, E2, T, LH and FSH, and the patients with qi and Yin deficiency syndrome as well as an elevated PROG level had the lowest C-peptide level, HOMA-β and HOMA2-IR and the highest HOMA-IS, PROG, E2, T, LH and FSH. An elevated PROG level is closely related to islet cell dysfunction and TCM syndrome types in male patients with T2DM.

Successful embryo transfer from Hokkaido native pony after artificial insemination with frozen semen.

There has been no report of equine embryo transfer in Japan for the last 24 years. Our objective was to establish an effective protocol for embryo transfer in domestic horse. A Hokkaido native pony was bred by deep-horn artificial insemination with frozen semen from a Connemara pony. Embryo collection was performed using a non-surgical method on day 7. Two embryos were obtained from three flushes (67% recovery) and were transferred fresh into crossbred recipient mares. Both recipient mares were diagnosed pregnant (100% pregnancy rate) 5 days after embryo transfer and had normal progesterone levels until the end of the observation on day 35 of gestation. This is the first successful embryo transfer in Japan by artificial insemination using frozen semen. Embryo transfer technology could be extremely useful in improving the productivity of Japanese domestic and special riding horses.

Seipin deficiency leads to defective parturition in mice.

Seipin is an integral endoplasmic reticulum membrane protein encoded by Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2/Bscl2) gene. Seipin deficiency results in lipodystrophy, diabetes, muscle hypertrophy, and male infertility in both human and mouse. Seipin function in female reproduction is unknown. Bscl2-/- dams had normal embryo implantation and body weight gain during pregnancy but reduced delivery rates from 2nd to 4th pregnancies and reduced numbers of pups delivered from 1st to 4th pregnancies. Characterization of first pregnancy revealed increased gestation period and parturition problems, including uterine prolapse, difficulty in delivery, undelivered fetuses, and undelivered tissues in Bscl2-/- females. Bscl2-/- uterine weight was comparable to control at 3 weeks old but significantly increased with myometrial hypertrophy at 10 months old. In situ hybridization revealed relatively low level of Bscl2 mRNA expression in myometrium throughout pregnancy and postpartum but high level of expression in uterine luminal epithelium, suggesting that systemic effect (e.g. elevated glucose and insulin levels) rather than local seipin-deficiency in myometrium might be a main contributing factor to myometrial hypertrophy. On near-term gestation day 18.5 (D18.5), Bscl2-/- females had normal levels of serum progesterone and 17β-estradiol, indicating functional ovary and placenta. Proliferating Cell Nuclear Antigen (PCNA) staining showed minimal myometrial cell proliferation in both D18.5 Bscl2+/+ and Bscl2-/- uteri. There was strong LC3 immunostaining in Bscl2+/+ and Bscl2-/- peripartum myometrium and increased LC3 staining in Bscl2-/- peripartum uterine luminal epithelium, suggesting a potential role of seipin in regulating autophagy in uterine luminal epithelium but not myometrium. This study demonstrates an association of seipin with myometrium and parturition.

The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium

To evaluate the effects of high progesterone prior to oocyte retrieval on the genomic profile of peri-implantation endometrium, we conducted this single-center, prospective cohort study. Depending on whether or not the progesterone level on the day of hCG administration and the day after hCG administration were elevated, a total of 20 women undergoing IVF treatment who did not have fresh embryo transfer were included: Group 1 refers to subjects with normal progesterone level on both days; Group 2 refers to subjects with normal progesterone level on the day of hCG administration and high progesterone level on the day after hCG administration; Group 3 refers to subjects with high progesterone level on the day of hCG administration and normal progesterone level on the day after hCG administration; Group 4 refers to subjects with high progesterone level on both days. Five subjects were included in each group. Endometrial samples were obtained 7days after hCG administration. We found that high progesterone level prior to oocyte retrieval predominantly affected components of the NK cell mediated cytotoxicity pathway in the endometrium and that significant differences were only seen when progesterone measurements on both the day of and day after hCG administration were considered together.

Prognostic role of hyperhomocysteinemia in prolonged pregnancies according to the ROC-analysis findings

Objective: To evaluate the clinical and prognostic role of homocysteine in pregnant women with prolonged pregnancy. To study the features of delayed delivery and perinatal outcomes in this case, we analysed 96 pregnant women with prolonged delivery during 2013-2015., who gave birth to children in the period of 41-42 weeks. As a control group we examined 41 pregnant women, who, for clinical and demographic characteristics, did not differ from the comparison group, but with delivery in time 37-40 weeks. Thus, depending on the patient's gestational age they were divided into 2 groups: group 1 included 41 patients, delivering with the term of gestation 37-40 weeks, group 2 – 96 patients, delivering after 41- 42 weeks of pregnancy. The level of homocysteine in the group with prolonged pregnancy (10,76 mmol/L) exceeded the figure in the control group significantly (7,72 mmol/L) (p&lt;0.05). Risk assessment by ROC-analysis and logistic regression allows to calculate the critical value of homocysteine (9,5 mmol/L) which is associated with a high risk of complications (area under the ROCcurve is more than 90 %). The proposed method for predicting complications by using homocysteine serum level has a very high sensitivity (87,5 %), specificity (84,21 %), positive and negative predictive significance (85,37 % and 86,49 %, respectively) relative to the diagnosis of high risk complications of prolonged pregnancy. Women with high homocysteine reliably showed adverse changes in the functioning of the fetoplacental complex. According to the chi-squared, the homocysteine level over 9,5 mmol/L recorded statistically significantly fewer pregnant women with normal levels of progesterone (χ2=17,2 at p&lt;0,01). According to the conducted regression analysis of the relationship between size of homocysteine and pulsation index (PI) cord statistically approximated logarithmic regression model (exponential) type pulsation index PI=-0,04+0,89*log10(homocysteine). Designed interdependence which is gradually growing exponentially, shows that more than half the dispersion characteristics pulsation index (PI) cord can be explained by the change in the concentration of homocysteine blood, and the greatest growth function was observed in the range of more than 14 mg/l of homocysteine, where in most cases there were a disorder in the uterine blood flow (PI over 1 IU).

93 BLASTOCYST BISECTION TO MULTIPLY BIOPSIED AND VITRIFIED BOVINE EMBRYOS

Dairy cattle breeding schemes increasingly integrate embryo-based genomic selection to accelerate genetic gain. In contrast to the single offspring produced with conventional animal-based genomic selection, multifactorial IVF between elite parents increases genotypes for selection. Genetically superior embryos are identified from biopsies, and only those with the desired genotypes are transferred. To manage the logistics of such schemes, and enable seasonally born progeny, the cryo-preservation of embryos after biopsy and before embryo transfer is critical. Here, we compare 2 methods of cryo-preserving biopsied Day 7 blastocysts and report results from bisecting blastocysts to increase the number of selected embryos for transfer. Abattoir-sourced oocytes were matured in vitro and fertilized with sperm from a single sire. Embryos were cultured for 7 days in a modified Synthetic Oviduct Fluid medium. Approximately 15 cells were biopsied from the mural trophectoderm of grade 1 and 2 blastocysts in Embryo Hold medium minus BSA, using a micro-surgical blade (Bioniche Animal Health, Athens, GA, USA). Following biopsy, each blastocyst was cultured in Embryo Hold with 3 mg mL−1 BSA for ~2 h at 38.5°C to allow for re-expansion. In Experiment 1, embryos were randomly assigned to 1 of 2 cryo-preservation treatments: conventional slow freezing or the Cryologic vitrification method (CVM). Slow freezing entailed freezing in 1.5 M ethylene glycol and 0.1 M sucrose. The CVM involved a 2-step vitrification protocol, with 15% of both ethylene glycol and dimethyl sulphoxide in the final solution comprising Embryo Hold, 20% FCS, 1 M sucrose, and 0.1 mM Ficoll (GE Healthcare). Selected embryos were thawed/warmed and transferred in pairs to the uterine horn ipsilateral to the corpus luteum of each synchronized recipient heifer. In Experiment 2, each biopsied blastocyst was individually vitrified using CVM. Following warming, blastocysts were bisected into approximately equal halves. After ~2 h recovery, pairs of demi-embryos were transferred to recipients categorized with either normal (&gt;2.5, &lt;7 ng mL−1) or low (≥2, &lt;2.5 ng mL−1) plasma progesterone concentrations on Day 5 after oestrus. Embryo survival in both experiments was monitored by ultrasonography of fetal heartbeats up to Day 65 of gestation. Statistical significance was determined using Fisher’s exact test. In Experiment 1, embryo survival on Day 65 was significantly greater with CVM than slow freezing (25/54 = 46% v. 9/54 = 17%; P = 0.002). In Experiment 2, there was no significant difference in the number of fetuses as a percentage of original blastocysts, regardless of normal versus low progesterone levels (13/22 = 59% v. 4/9 = 44%, respectively). In conclusion, vitrification is superior for cryo-preserving biopsied blastocysts, possibly reducing cryo-damage compared with conventional slow freezing, and achieves rates of in vivo development similar to fresh IVF embryos. Embryo bisection potentially provides only a modest increase in the probability of generating a calf from each valuable, genomically selected embryo. Improving embryo competency and other methods of multiplication may maximize this likelihood.

Expression of VEGF angiogenic factors in uterine natural killer cell around the time of embryo implantation of women with high or normal progesterone level prior to oocyte retrieval

To investigate the relationship between uterine natural killer (uNK) cell number and the expression of VEGF angiogenic factors in uNK cell in women with high or normal progesterone level prior to oocyte retrieval.

Progesterone Therapy, Endothelial Function and Cardiovascular Risk Factors: A 3-Month Randomized, Placebo-Controlled Trial in Healthy Early Postmenopausal Women

BackgroundProgesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation.Methods and ResultsWe conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003–2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1–11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55±4 years, body mass index 25±3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487±189%, n = 18) compared with placebo (408±278%, n = 16) (95% CI diff [−74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (−0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo.ConclusionsResults indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change).Trial RegistrationClinicalTrials.gov NCT00152438

Androgen-producing steroid cell ovarian tumor in a young woman and subsequent spontaneous pregnancy

To describe the presentation and fertility sparing treatment of a young woman found to have a steroid cell tumor not otherwise specified (NOS) and her spontaneous pregnancy and delivery shortly after surgery. A 20-year-old Hispanic female presented with hirsuitism, virilization, and elevated androgen levels (testosterone 328ng/dL) and was wrongly diagnosed with polycystic ovarian syndrome. Four months later she sought a second opinion. Her androgens were as follows: testosterone level 485ng/dL, androstenedione 1,738ng/dL and DHEA 1,459ng/dL. She had normal levels of progesterone, estradiol, and DHEA-SO4. On transvaginal ultrasound she had a solid-appearing right ovarian mass. She underwent fertility sparing surgery with a laparoscopic right oophorectomy. Gross and histological pathology confirmed a benign steroid cell tumor NOS. She had rapid normalization of all androgens 13days after surgery. She had spontaneous resumption of menses 4months later. She conceived despite using emergency contraception approximately 9months following surgery and delivered a healthy boy at term without complication. Prompt evaluation for an androgen producing tumor should be performed when testosterone levels are greater than 200ng/dL. Pregnancy following removal of this rare tumor has not previously been reported.

Premenstrual Dysphoric Disorder and the Brain

Premenstrual Dysphoric Disorder and the Brain

Efficacy of treatment of vulva cancer patients and analysis of their hormonal status.

e21127 Background: hormonodependency of vulva is wellknown. This broughtusto study hormonal status of vulva cancer patients depending on treatment efficacy Methods: we present comparative analysis of hormonal status of vulva cancer patients in two groups: group 1 (50 patients) without relapse of the disease in 5-year period, and group 2 (35 patients) with relapse developed within the first year. Blood concentrations of testosterone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone were determined in all patients under study by means of radiometric methods. Estrone, estradiol, estriol with subsequent calculation of their sum were determined in daily urine by Brown method. Results: In the presence of effect (group 1) initial total amount of estrogens was twice as large than in its absence. In group 1 estradiol concentration exceeded the corresponding parameter of group 2 by three times(7.6±0.6 &amp; 1,4±0.3,p&lt;0.001). The amount of secreting estriol at positive result was almost twice higher than in cases of absence of the effect(10.02±1.7 &amp; 4.6±0.49, p&lt;0.001). The groups differed by secretion levels of follicle-stimulating and luteinizing hormones. Blood concentration of these hormones was lower in negative results that in positive. Distinct differences were also observed in progesterone and prolactin levels. In the group with positive result of treatment progesterone concentration was much higher than in the group without treatment effect. On the contrary, prolactin concentration in group 1 was significantly less than in group 2. The highest degree of reliability of quantitative indices related to treatment efficacy was observed for progesterone. Positive result of corresponding treatment may be predicted at normal initial progesterone level, and negative result at its low level (3-4 times lower than the norm). Another parameter - blood concentration of prolactin - can be used almost with the same degree of reliability. Conclusions: results of the study allow to suggest an existence of interrelation between treatment efficacy of vulva cancer patients and functional activity of hypophysis-gonadal system. Some of its parameters may be used to predict results of complex treatment of vulva cancer patients.

Pseudohypoaldosteronism Masquerading as Congenital Adrenal Hyperplasia

A 15-day- old male infant presented with features suggestive of congenital adrenal hyperplasia (CAH). But on detailed investigation, he had normal 17-OH Progesterone and high aldosterone levels. Infant also had right sided hydronephrosis and associated urinary tract infection. Hence, a diagnosis of secondary pseudohypoaldosteronism was made. There was good response to sodium chloride supplementation and he was thriving well on follow up. While evaluating any infant with suspected CAH, one should consider secondary pseudohypoaldosteronism, especially when risk factors like urinary tract obstruction or UTI coexists.

Suppression of Follicular Rupture With Meloxicam, A Cyclooxygenase-2 Inhibitor: Potential for Emergency Contraception

The preferred treatment for emergency contraception at present is the synthetic progestogen levonorgestrel. Although this drug is widely available, women in some countries have little access to it due to restrictions imposed by conservative groups. Recent evidence has shown that levonorgestrel may have no contraceptive effect when taken after the ovulatory process has been triggered; this suggests that contraceptive failures with this drug may result from delayed administration. A number of studies have provided evidence that nonsteroidal anti-inflammatory drugs and specifically, cyclooxygenase-2 (COX-2) inhibitors, can prevent or delay follicular rupture. In a recent placebo controlled, double-blind, crossover study, daily administration of a partially selective COX-2 inhibitor, meloxicam, for 5 days at the onset of the luteinizing hormone (LH) surge significantly delayed follicular rupture. One advantage of using a COX-2 inhibitor to prevent or delay follicular rupture and inhibit the LH surge in comparison with using levonorgestrel is that COX-2 inhibition does not suppress the luteal phase. Accordingly, meloxicam should maintain the normal oscillations of ovarian steroids and preserve normal menstrual cycles. Other benefits of using COX-2 inhibitors include their accessibility over-the-counter in many countries and low cost as well as their improved safety profile with short-term treatment in women of reproductive age compared with steroid hormones. This single center, randomized, Phase I, double-blind, crossover study assessed the efficacy of meloxicam administered during the late follicular phase to prevent or delay follicular rupture when given very close to or after the LH started. The study subjects—27 healthy surgically sterilized volunteers (18―40 years old) with regular menstrual cycles—received oral doses of meloxicam 15 or 30 mg/d for 5 consecutive days starting when the leading follicle had reached 18 mm diameter. The participants underwent 3 cycles—first a drug-treatment cycle, a resting cycle, and then a second drug-treatment cycle. The primary study outcomes were the occurrence of follicular rupture, serum levels of LH, progesterone and estradiol, and the incidence of adverse events. Of the 27 volunteers, 22 completed the study. Dysfunctional ovulation occurred in 50% (11/22) of the cycles in women treated with the 15 mg/d dose and in 91 % of the cycles in women receiving the 30 mg/d dose (P = 0.0068). All women had normal progesterone levels during luteal phase; the mean maximal value was 42 ± 4.1 nmol/L for the 15 mg/d group and 46.8 ± 2.6 nmol/L for the 30 mg/d group. No changes were found in menstrual cycle length or in LH and estradiol levels. Serious adverse events were not observed. The findings of this pilot study suggest that the administration of meloxicam 30 mg/d for 5 consecutive days during the late follicular phase is effective, safe, and may be an alternative to levonorgestrel for emergency contraception.

Loss of Cannabinoid Receptor CB1 Induces Preterm Birth

BackgroundPreterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Methods and FindingsExploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.ConclusionsCB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in aberrant corticotrophin-releasing hormone and corticosterone activities prior to parturition, suggesting that CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis.