Progesterone Capsules Research Articles

Additional Daily Intramuscular Progesterone for Luteal Phase Support does not Improve Live Birth Rates of Programmed Frozen-Thawed Embryo Transfer Cycles

This retrospective cohort study aims to investigate whether additional daily intramuscular progesterone (IMP) for luteal phase support improves live birth rates of programmed frozen-thawed embryo transfer (FET) cycles. The study was conducted at a tertiary level university hospital assisted reproductive technology (ART) center between January 2014 and Jan 2021. Six hundred four infertile patients with single-day 5-6 frozen-thawed blastocyst embryo transfer were enrolled in the study. All patients received either 8% micronized vaginal gel or vaginal progesterone capsules for luteal phase support. Intramuscular progesterone was added to vaginal progesterone depending on the in vitro fertilization (IVF) specialist’s choice. Luteal phase support (LPS) was started 6 days before transfer in frozen-thawed cycles and continued until the end of the first trimester. Cycles were compared depending on vaginal progesterone types (8% gel vs. capsule) and the presence of intramuscular progesterone. The primary outcome was the live birth rate. A total of 604 FET cycles were enrolled. Using 8% micronized progesterone or progesterone capsules did not change the live birth rates (24% vs. 25.9%). As the main result, intramuscular progesterone support with vaginal progesterone compared with only vaginal progesterone did not improve the live birth results (22% vs. 24%). In conclusion, this study demonstrated that routine IMP progesterone given in combination with vaginal progesterone does not improve ART outcomes. This combination may be beneficial in a selective population with a monitored luteal phase. Using any form of vaginal progesterone alone is adequate for LPS.

Resource utilization of expired progesterone medicines as flow improver for waxy crude oils

At present, the treatment of expired medicines mainly involves burning, which means waste of resources and carbon dioxide emissions, and it does not comply with the concept of resource recycling. In this study, in order to explore the resource utilization pathways of expired medicines, progesterone drugs were evaluated as crude oil flow improvers as an example. The results shows that progesterone injection (PI) and progesterone capsule (PC) both act as viscosity reducer and pour point depressant in different crude oil, and 500 ppm PI and 300 ppm PC are the best dosage respectively. 500 ppm PI can reduce the viscosity of HN oil sample by 60.40%, and depress the pour point by 8.5 °C. 300 ppm PC can reduce the viscosity of HN oil by 54.7%, and depress the pour point by 10.9 °C. Furthermore, through DSC and wax crystal morphology analysis, the possible mechanism of this expired medicine as crude oil flow improver was further discussed. Finally, considering the costs of concentration, transportation, treatment, processing and other links, the possible cost of crude oil flow improver was summed up, and its market feasibility was analyzed. This study provides a reference case for the resource utilization of expired medicines.

Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial.

To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Supplementary dydrogesterone is beneficial as luteal phase support in artificial frozen-thawed embryo transfer cycles compared to micronized progesterone alone.

The number of frozen embryo transfers increased substantially in recent years. To increase the chances of implantation, endometrial receptivity and embryo competency must be synchronized. Maturation of the endometrium is facilitated by sequential administration of estrogens, followed by administration of progesterone prior to embryo transfer. The use of progesterone is crucial for pregnancy outcomes. This study compares the reproductive outcomes and tolerability of five different regimens of hormonal luteal phase support in artificial frozen embryo transfer cycles, with the objective of determining the best progesterone luteal phase support in this context. This is a single-center retrospective cohort study of all women undergoing frozen embryo transfers between 2013 and 2019. After sufficient endometrial thickness was achieved by estradiol, luteal phase support was initiated. The following five different progesterone applications were compared: 1) oral dydrogesterone (30 mg/day), 2) vaginal micronized progesterone gel (90 mg/day), 3) dydrogesterone (20 mg/day) plus micronized progesterone gel (90 mg/day) (dydrogesterone + micronized progesterone gel), 4) micronized progesterone capsules (600 mg/day), and (5) subcutaneous injection of progesterone 25 mg/day (subcutan-P4). The vaginal micronized progesterone gel application served as the reference group. Ultrasound was performed after 12-15 days of oral estrogen (≥4 mg/day) administration. If the endometrial thickness was ≥7 mm, luteal phase support was started, up to six days before frozen embryo transfer, depending on the development of the frozen embryo. The primary outcome was the clinical pregnancy rate. Secondary outcomes included live birth rate, ongoing pregnancy, and miscarriage and biochemical pregnancy rate. In total, 391 cycles were included in the study (median age of study participants 35 years; IQR 32-38 years, range 26-46 years). The proportions of blastocysts and single transferred embryos were lower in the micronized progesterone gel group. Differences among the five groups in other baseline characteristics were not significant. Multiple logistic regression analysis, adjusting for pre-defined covariates, showed that the clinical pregnancy rates were higher in the oral dydrogesterone only group (OR = 2.87, 95% CI 1.38-6.00, p=0.005) and in the dydrogesterone + micronized progesterone gel group (OR = 5.19, 95% CI 1.76-15.36, p = 0.003) compared to micronized progesterone gel alone. The live birth rate was higher in the oral dydrogesterone-only group (OR = 2.58; 95% CI 1.11-6.00; p=0.028) and showed no difference in the smaller dydrogesterone + micronized progesterone gel group (OR = 2.49; 95% CI 0.74-8.38; p=0.14) compared with the reference group. The application of dydrogesterone in addition to micronized progesterone gel was associated with higher clinical pregnancy rate and live birth rate and then the use of micronized progesterone gel alone. DYD should be evaluated as a promising LPS option in FET Cycles.

Retracted: Clinical Efficacy of Assisted Reproductive Technology Combined with Progesterone Capsules in the Treatment of Infertility Caused by Diminished Ovarian Reserve and Its Influence on Serum FSH, E2, and LH Levels of Patients.

[This retracts the article DOI: 10.1155/2022/5319172.].

P-678 Does gonadotropin dose adjustment in inadequate ovarian response during controlled ovarian hyperstimulation improve the live birth rates of patients with diminished ovarian reserve?

Abstract Study question Does gonadotropin dose adjustment in inadequate ovarian response during controlled ovarian hyperstimulation improve the live birth rates of patients with diminished ovarian reserve? Summary answer The increasing dose adjustment of the gonadotropin according to the ovarian response during COH in DOR provides similar live birth rates to the fixed-dose group. What is known already Since the poor ovarian response is associated with low pregnancy rates and high cycle cancellation rates, the ovarian response should be predicted, especially for stimulation protocol and gonadotropin dose adjustment before COH is initiated. On the other hand, the predicted gonadotropin dose may not be enough for the ovarian response, and the dose adjustment may be required. Nevertheless, the literature has conflicting results on whether dose adjustment during COH improves the pregnancy results. Study design, size, duration This retrospective cohort study was conducted at a tertiary university hospital's ART (assisted reproductive technologies) center. The electronic database of the ART center was screened between the years 2012-2021, and the DOR patients who underwent ICSI-ET (intra-cytoplasmic sperm injection – embryo transfer) were selected. Bologna criteria were used to determine the diminished ovarian reserve. Patients were divided into two groups depending on the presence of dose adjustment on the first ultrasound control during COH. Participants/materials, setting, methods Women who underwent single–fresh good quality (Gardner A or B) blastocyst transfer and aged between 18-40 years, without male infertility and endometrial pathology were included in, and after exclusion, 498 patients were enrolled in the study. Flexible antagonist protocol was used for COH. A vaginal micronized progesterone capsule (3x200 mg) was prescribed for luteal phase support after oocyte retrieval. Live birth rate was determined as the singleton live birth after the 24th week of pregnancy. Main results and the role of chance There were 188 patients in the dose adjustment (DA) group and 310 patients in the fixed-dose (FD) group. The demographic parameters were similar between the groups (Age, Body Mass Index, Ovarian Reserve Parameters). The mean women age was 33.8+4 in the DA group and 33.6+4.1 in the FD group (p = 0.6). The started gonadotropin dose was similar in both groups (300 IU). The type of gonadotropin was mostly HMG in the DA group (67% in DA vs. 48% in the FD group, p = 0.01). The median dose adjustment on the first control was +75 IU in the DA group, and as expected, the total gonadotropin consumption was significantly higher in the DA group (Median values; 3900 vs. 3000 IU, p &amp;lt; 0.01). The follicle output rates, follicle to oocyte indexes, and the embryology parameters were comparable between the groups (number of picked up oocytes, metaphase-2 oocytes, and 2PN embryos). The positive pregnancy rate was 19.7% (36/188) in the DA group vs. 19.1% (61/310) in the FD Group (p = 0.4). The primary outcome of the study; live birth rates were 12% in the DA group vs. 9% in the FD group, and the results were statistically similar (p = 0.3). Limitations, reasons for caution Retrospective design and the sample size limit the power of the study. Wider implications of the findings Our study showed that the gonadotropin dose adjustment in inadequate ovarian response during COH provides similar live birth rates to the fixed-dose group. In patients with inadequate response, dose adjustment may be a necessary action. Trial registration number Not applicable

Clinical Efficacy of Assisted Reproductive Technology Combined with Progesterone Capsules in the Treatment of Infertility Caused by Diminished Ovarian Reserve and Its Influence on Serum FSH, E2, and LH Levels of Patients.

Objective To explore the clinical efficacy of assisted reproductive technology (ART) combined with progesterone capsules in the treatment of infertility caused by the diminished ovarian reserve (DOR) and its influence on serum FSH, E2, and LH levels of patients. Methods In the manner of retrospective study, the data of 120 patients with infertility caused by DOR admitted to our hospital (February 2019–February 2020) were retrospectively analyzed, and the patients were equally divided into the experimental group and the control group according to the order of admission. All patients underwent in vitro fertilization and embryo transfer (IVF-ET), and the experimental group was received progesterone capsules at the same time. Ovarian-related indexes, follicular development, serum hormone levels, and pregnancy outcomes were compared between both groups. Results After treatment, compared with the control group, ovarian-related indexes and follicular development in the experimental group were conspicuously better (P < 0.001). In the experimental group, the FSH level was (5.99 ± 1.20) U/L, the E2 level was (540.12 ± 3.54) ng/L, and the LH level was (3.10 ± 0.35) U/L after treatment, which was significantly better than those of the control group (P < 0.001). After treatment, compared with the control group, the clinical pregnancy rate in the experimental group was conspicuously higher (P < 0.05), and the abortion rate in the experimental group was conspicuously lower (P < 0.05). No obvious difference was observed in multiple births rate between the two groups (P > 0.05). Conclusion ART combined with progesterone capsules can improve serum hormone levels, ovarian function, follicular development, and clinical pregnancy rate for patients with infertility caused by DOR, which should be applied in practice.

Adding Weekly Intramuscular Progesterone to a Twice Daily Vaginal Progesterone Capsule for Luteal Phase Support in IVF/ICSI Cycles Results in Similar Live Birth Rates.

ObjectiveTo compare pregnancy outcomes in patients undergoing artificial reproductive treatment (ART) and fresh embryo transfer (ET) who received twice-daily vaginal progesterone capsule (Cyclogest) alone verses twice daily vaginal progesterone capsule (Cyclogest) plus weekly intramuscular Hydroxyprogesterone Capronate (Proluton depot) for luteal phase support.MethodsA retrospective cohort study that included 1162 patients who completed fresh ART/ET cycle from January 2015 to April 2018. Vaginal Cyclogest 400 mg twice daily was given to 985 patients following oocytes retrieval; whereas 177 patients received weekly intramuscular Proluton depot 250 mg in addition to twice-daily Cyclogest. The primary outcome was live birth rate. The secondary outcomes included biochemical pregnancy rate, clinical pregnancy, biochemical, and early and late pregnancy loss.ResultsThere was no difference between the twice-daily vaginal progesterone and the addition of weekly intramuscular progesterone injections to the twice-daily vaginal progesterone regarding a positive pregnancy test (40.5% and 46.9%, respectively, p=0.112). There was no statistical difference in live birth rates between the groups (24% for group one, 26% for group two, p=0.582).ConclusionsThe administration of weekly intramuscular progesterone in addition to twice-daily vaginal progesterone capsule for luteal phase support post ART cycle does not result in higher live birth rate.

P–654 What is the best luteal phase support in frozen-thawed embryo transfer cycle?

Abstract Study question What is the best progesterone administration for luteal phase support (LPS) in frozen-thawed embryo transfer cycle? Summary answer Different modes of hormonal luteal phase support do not affect clinical pregnancy rate (CPR) or live birth rate (LBR) in frozen-thawed embryo transfer (FET) cycles. What is known already FET has increased substantially over the last years. To support implantation, endometrial and embryo maturities must be synchronized; therefore, endometrial and follicular maturation are monitored either within the artificial cycle. Estrogen and progesterone are sequentially administered. The optimal endometrial preparation strategy remains unclear; this study aims to compare the reproductive and pregnancy outcomes between five different regimens of hormonal LPS for FET treatment. Study design, size, duration Single centre retrospective cohort study conducted between 2013 and 2019. Included were women (N = 402) aged 18–45 years undergoing FET. After an optimal endometrial preparation and endometrial thickness, the LPS was started. Thereafter, five different progesterone applications were compared: (1) oral dydrogesterone (10mg tid), (2) vaginal progesterone gel (90mg/d), (3) dydrogesterone (10mg tid) plus vaginal progesterone gel (90mg/d), (4) vaginal progesterone capsules (200mg tid), or (5) subcutaneous injection of 25mg daily. Participants/materials, setting, methods An ultrasound was performed 14 days of estrogene ( &amp;gt; =4mg/d) preparation. If the endometrial thickness was ≥7 mm and there was no dominant follicle, luteal support commenced four days before FET. Fourteen days after transformation, a serum beta-hCG test was performed. If positive (&amp;gt; 50 IU/L), a transvaginal ultrasound was performed to confirm clinical pregnancy, defined as gestational sac with fetal heart movement. CPR was assessed and delivery reports for LBR were collected later. Main results and the role of chance In total, 402 patients on an artificial cycle were included (mean age, 35 years (y); range, 26–46 y; standard deviation, 4.1 y). No differences in endometrial thickness and cause of infertility were found between groups. Multivariate logistic regression analysis revealed that the odds ratios (ORs) with 95% confidence intervals (CIs) for the CPR was significantly higher in the dydrogesterone only group (OR, 3.25; 95% CI, 1.7–6.2; p &amp;lt; 0.001) and in the combined group (3) (OR, 7.55; 95% CI, 2.7–21.10; p &amp;lt; 0.001). Statistically significant differences in live birth rate could not be found between the five groups; they were 33%, 54%, 8.3%, 4%, 0% for groups 1, 2, 3, 4, and 5 respectively. Overall satisfaction and tolerability were significantly higher in oral dydrogesterone compared to the vaginal progesterone. Limitations, reasons for caution This is a retrospective single-center study. Also, potentially confounding variables like ethnicity, parity, BMI were not accounted for, possibly contributing to bias. Further prospective randomized studies are needed. Wider implications of the findings: Oral dydrogesterone was found to be effective with equal CPR and LBR. Benefit is well-tolerated and accepted among patients; however we did not observe significant differences in the rates of live birth between the five regimens for used for LPS in women undergoing frozen-thawed embryo transfers. Trial registration number BASEC Switzerland 2020–01527

Quantification Analysis of Progesterone Based on Terahertz Spectroscopy

Progesterone is a natural progestational hormone secreted by the corpus luteum and placenta that protects the growth of the fetus in the early stage. It is also applied to the study on the treatment of human central nervous system diseases, which proved to have high clinical medicinal value. The present detection methods of progesterone concentration, such as high-performance liquid chromatography and enzyme-linked immunosorbent assay, have the disadvantages of high consumption, cumbersome procedures, and expensive equipment. Here, the terahertz spectroscopy is applied to detect the medicinal concentration of progesterone. First, the characteristic peaks of progesterone are 1.24, 1.64, and 2.12 THz, determined by the density functional theory calculation and experimental collection of terahertz spectra. Then, the peak height and peak area of the above characteristic peaks are used to establish a linear correlation model with the concentration of progesterone injection, and the coefficient of determination (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ), in this model, is greater than 0.95. Meanwhile, we adopt Raman spectroscopy technology and got the R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of 0.71, which is not so good as terahertz spectroscopy. Furthermore, multivariate curve resolution-alternating least square is used to analyze the composition of progesterone in progesterone capsules. The result shows that the error rate between the predicted concentration of progesterone and the real one is less than 5%. Therefore, terahertz spectroscopy provides a new way for the detection of progesterone drug content.

Breast effects of oral, combined 17β-estradiol, and progesterone capsules in menopausal women: a randomized controlled trial.

Objective:To evaluate the effect of a single-capsule, bioidentical 17β-estradiol (E2) and progesterone (P4) hormone therapy on mammograms and breasts in postmenopausal women after 1 year of use.Methods:In the 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter REPLENISH trial, postmenopausal women (40-65 y) with moderate to severe vasomotor symptoms and a uterus were randomized to four active daily dose groups of E2/P4 (TX-001HR) or a placebo group. Mammograms were performed and read locally at screening (or ≤6 months before first dose) and at study end using BI-RADS classification. Incidence of abnormal mammograms and breast adverse events was evaluated.Results:All but 8 (0.4%) mammograms at screening were normal (BI-RADS 1 or 2). At 1 year, 39 (2.9%) of the 1,340 study-end mammograms were abnormal (BI-RADS 3 or 4); incidence was 1.7% to3.7% with active doses and 3.1% with placebo. Breast cancer incidence was 0.36% with active doses and 0% with placebo. Breast tenderness was reported at frequencies of 2.4% to 10.8% with active doses versus 0.7% with placebo, and led to eight study discontinuations (1.6% of discontinuations in active groups).Conclusions:In this phase 3 trial of a combined E2/P4, results of secondary outcomes suggest that E2/P4 may not be associated with increased risk of abnormal mammograms versus placebo, and the incidence of breast tenderness was low relative to most of the rates reported in other studies using hormone therapy.

Intravaginal administration of progesterone using a new technique for sustained drug release in goats.

The objective of the present study was to develop and evaluate a sustained release vaginal progesterone (P4) capsule containing a mixture of mucoadhesive polymer and silicone fluid. Goats were administered a gelatin capsule containing 0.4 g of P4 mixed in silicone fluid and either a hydroxypropylmethylcellulose (HM) or polyaclil starch (PA) base. The mean plasma P4 concentrations at 2 and 12 h after administration were significantly higher in goats treated with PA capsules than in those with HM capsules. The plasma P4 concentrations in goats treated with HM capsules increased and remained above 1.0 ng/ml for 96 h after administration, whereas the plasma P4 concentrations in goats treated with PA capsules remained above 1.0 ng/ml for only 24 h after administration. In the next experiment, an HM capsule was attached to a silicone device and inserted in the vagina for 10 days. The plasma P4 concentration remained similar to that of the natural luteal phase for 9 days. These results suggest that a mixture of mucoadhesive polymer and silicone fluid has the potential to be applied clinically as a sustained release base for estrus synchronization or hormonal therapy.

Comparison of oral dydrogesterone and vaginal micronized progesterone for luteal phase support in intrauterine insemination

This study aims to compare the pregnancy outcomes of vaginal micronized progesterone capsules with oral dydrogesterone in subjects with unexplained subfertility who are undergoing IUI in conjunction with ovarian stimulation by using rFSH. A total of 432 patients with unexplained subfertility who underwent IUI in conjunction with ovarian stimulation were enrolled in this retrospective study. Patients were randomized into two groups: (1) dydrogesterone or (2) vaginal micronized progesterone capsules, for luteal phase support. Clinical pregnancy and live birth were the primary outcome measures of the present study. Dydrogesterone was used in 233 participants (54%) and 337 cycles, while 199 participants (46%) and 233 cycles received vaginal micronized progesterone capsule treatment. The proportion of clinical pregnancies (7.4% vs. 10.2%, p = .213), live births (68% vs. 73%, p = .286) were similar in the two groups. Oral dydrogesterone and vaginal micronized progesterone provide similar pregnancy outcomes in terms of clinical pregnancy and live birth rates in women undergoing IUI in conjunction with ovarian stimulation with rFSH. Given the simple and easy administration, lack of safety concerns and better patient tolerability, we suggest that oral dydrogesterone might be preferred for luteal phase support in IUI.

A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause

ABSTRACTIntroduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17β-estradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS.Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus.Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.

020 Bioidentical Combined Estradiol and Progesterone Capsules Improved Vaginal Dryness in Women with Vasomotor Symptoms

020 Bioidentical Combined Estradiol and Progesterone Capsules Improved Vaginal Dryness in Women with Vasomotor Symptoms

SAT-237 Combined Bioidentical Estradiol and Progesterone Capsules Improved Quality of Sleep in Postmenopausal Women with Vasomotor Symptoms

Difficulty sleeping is a common complaint of postmenopausal women. In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL), was shown to reduce moderate to severe hot flush frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. In this analysis, the effect of the E2/P4 capsules on “difficulty sleeping” in postmenopausal women experiencing hot flushes, was assessed by the menopause-specific quality of life (MENQOL) questionnaire and also analyzed by age. The phase 3 REPLENISH trial (NCT01942668), evaluated 4 daily doses of E2/P4 capsules in postmenopausal women (40-65 years, intact uterus) with vasomotor symptoms (VMS). Women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy); women with fewer/less severe VMS were randomized to active E2/P4 doses only for endometrial safety. MENQOL was administered at baseline, week 12, and months 6 and 12. The “difficulty sleeping” item was rated using a 7-item Likert scale ranging from “Not at all bothered” (analysis score of 2) to “Extremely bothered” (analysis score of 8) if difficulty sleeping was experienced, if not experienced, the score for the analysis was set to 1. Changes from baseline to week 12, and months 6 and 12 in all women (MITT population) were analyzed by ANCOVA between each E2/P4 groups vs placebo and stratified by age (pre-specified FDA subgroup; <55 and 55+). Treatment groups in the MITT population (n=1833) were E2/P4 1/100 (n=416), 0.5/100 (n=422), 0.5/50 (n=421), 0.25/50 (n=423) or placebo (n=151). The MITT population had a mean age of 55 years; in the <55-year group (n=927) mean age was 51.2 years and in the ≥55-year group (n=906) mean age was 58.1 years. Mean baseline scores for the “difficulty sleeping” item ranged from 5.1 to 5.8 points. In the MITT population, difficulty sleeping significantly improved from baseline with the three highest E2/P4 doses (1/100, 0.5/100, 0.5/50) compared with placebo at all timepoints (all, P<0.05), except for 0.5/50 at month 6. In women <55 years, the sleep difficulty item significantly improved from baseline at all timepoints with two E2/P4 doses (1/100 and 0.5/50) vs placebo. In women 55+ years, significant improvements from baseline were observed at week 12 with three E2/P4 doses (1/100, 0.5/100, 0.5/50) vs placebo. In REPLENISH, women treated with E2/P4 capsules containing 1 or 0.5 mg E2 demonstrated significant and sustained improvements in the MENQOL difficulty sleeping assessment, especially those <55 years. These data warrant further evaluation.

Drug use in patients with polycystic ovary syndrome at some hospital

Objective To provide some references for optimizing the treatment plans and improving the rational drug use in clinic investigating the drug application in outpatients with polycystic ovary syndrome (PCOS). Methods The data of prescriptions for the outpatients with PCOS treated at our hospital from June to December, 2017 were collected, sorted, and analyzed by Excel software. The DDDs and DDC were calculated; and the medication rationality was evaluated. Results Among the 1 373 prescriptions, the age of most the outpatients ranged from 26 to 30, which accounted for 46.76%. The top 5 therapeutic drugs in the respect of DDDs were ethinylestradione tablet (29.86%), estradiol valerate (17.92%), progesterone capsules (17.26%), metformin enteric-coated tablets (14.64%), and lyophilized powder (12.75%). The combination therapy accounted for 60.96% of all the prescriptions, in which the two-drug combination accounted for 40.13%. Conclusions The drug application for outpatients with PCOS at our hospital is basically reasonable. At present, our hospital mainly applies the hormone-related drugs, and combines with Chinese medicine and other adjuvant drugs to achieve the treatment and prevention of the disease. Key words: Polycystic ovary syndrome; Analysis of drug use; Rational drug use

Vaginal progesterone for the prevention of preterm birth and the risk of gestational diabetes

IntroductionWe aimed to determine whether daily vaginal progesterone use for the prevention of preterm birth has an effect on the incidence of abnormal glucose challenge test or gestational diabetes. Study designA retrospective study in a large referral center. Women with cervical length ≤ 25 mm were given 200 mg vaginal micronized progesterone capsules daily at bed time until 36 weeks` gestation or delivery. Each progesterone-treated woman was matched randomly with three untreated controls. The main outcome measures were; mean plasma glucose level following the glucose challenge test and the rate of abnormal 1-hour glucose challenge test. Secondary outcome was the rate of gestational diabetes. ResultsWe identified 108 progesterone-treated women that were matched by age and BMI to 324 controls during the same time period. The mean plasma glucose level following the glucose challenge test was similar in both groups (115.3 ± 33.8 mg/dL versus 109.2 ± 26.6 mg/dL). Despite a higher rate of an abnormal glucose challenge test in the progesterone-treated group compared to the control group (21.1% vs. 13.9%), it did not reach statistical significance. Similarly, we could not detect any difference in the rate of gestational diabetes in either the study or the control group (2.8% versus 2.5%). ConclusionDaily vaginal progesterone was not associated with higher rates of abnormal glucose challenge test or gestational diabetes. We are in a view that no earlier screening or diagnostic testing for gestational diabetes is required except the standard recommended schedule unless additional risk factors are present.

Demographics and the Placebo Response in the REPLENISH TRIAL: A Study of Vasomotor Symptoms [16OP

INTRODUCTION: High placebo responses (up to 61%) are reported in studies evaluating therapeutic agents for vasomotor symptoms (VMS). Placebo response rates by subgroups from a recently completed positive trial of an investigational combination of 17β-estradiol and progesterone capsule (TX-001HR) are presented. METHODS: REPLENISH was a phase 3, randomized, double-blind, placebo-controlled trial that evaluated safety/efficacy of TX-001HR in postmenopausal women, who had ≥50 moderate to severe hot flushes at baseline. 767 women received one of four TX-001HR daily doses or placebo; frequency and severity of VMS at baseline and weeks 4 and 12 were recorded by diary. Secondary endpoints were responder analyses and menopause-specific quality of life (MENQOL) questionnaire. Subgroup analysis of efficacy was performed on demographics. RESULTS: The placebo response rate was high (55%). Significant differences were observed in the placebo response rates between White (51%) and African American (65%) women at 12 weeks (P=.049). Mean age was similar; more African American women had BMI≥30 kg/m2 (32.4%) vs White (18.7%). More African American women were current smokers than White (41.5% vs 17.6%). Significant differences in responders (≥50% and ≥75%) and the MENQOL Vasomotor Domain were observed for all groups compared to placebo in the White population; no differences noted in African Americans due to high placebo rate. Baseline estradiol levels and compliance rates for African American and White women were similar. CONCLUSION: Large placebo responses occurred and more frequently in African Americans. Understanding factors that contribute to placebo responses are important in designing and assessing the efficacy of medications in clinical trials.

Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: a systematic review and meta-analysis.

ObjectiveTo identify, appraise, and summarize the evidence from randomized controlled trials (RCTs) comparing oral dydrogesterone to vaginal progesterone capsules for luteal-phase support (LPS) in women offered fresh or frozen embryo transfers following in vitro fertilization.MethodsTwo independent authors screened the literature for papers based on titles and abstracts, then selected the studies, extracted data, and assessed the risk of bias. Dydrogesterone and progesterone were compared based on risk ratios (RR) and the precision of the estimates was assessed through the 95% confidence interval (CI).ResultsAn electronic search performed on June 7, 2017 retrieved 376 records, nine of which were papers deemed eligible and included in this systematic review and quantitative analysis. Good quality evidence indicates that oral dydrogesterone provided at least similar results than vaginal progesterone capsules on live birth/ongoing pregnancy (RR=1.08, 95%CI=0.92-1.26, I2=29%, 8 RCTs, 3,386 women) and clinical pregnancy rates (RR 1.10, 95% CI 0.95 to 1.27; I2=43%; 9 RCTs; 4,061 women). Additionally, moderate quality evidence suggests there is no relevant difference on miscarriage rates (RR=0.92, 95%CI=0.68-1.26, I2=6%, 8 RCTs, 988 clinical pregnancies; the quality of the evidence was downgraded because of imprecision).ConclusionsGood quality evidence from RCTs suggest that oral dydrogesterone provides at least similar reproductive outcomes than vaginal progesterone capsules when used for LPS in women undergoing embryo transfers. Dydrogesterone is a reasonable option and the choice of either of the medications should be based on cost and side effects.