Progesterone In Women Research Articles

Cervical Pessary Versus Vaginal Progesterone in Women With a Singleton Pregnancy, a Short Cervix, and No History of Spontaneous Preterm Birth at Less Than 34 Weeks’ Gestation: Open Label, Multicentre, Randomized, Controlled Trial

Cervical Pessary Versus Vaginal Progesterone in Women With a Singleton Pregnancy, a Short Cervix, and No History of Spontaneous Preterm Birth at Less Than 34 Weeks’ Gestation: Open Label, Multicentre, Randomized, Controlled Trial

Social Orientation in the Luteal Phase: Increased Social Feedback Sensitivity, Inhibitory Response, Interpersonal Anxiety and Cooperation Preference.

Cyclical fluctuations of the ovarian hormones estrogen (E2) and progesterone (PROG) have multiple effects on reproduction and development. However, little is known about the roles of E2 and PROG in women's social behaviors. Here, based on evolutionary theory suggesting social sensitivity and inhibition ability are conductive to maintaining social relationships, we provide evidence for the association between menstrual phases and social orientation. In Study 1, 78 women provided saliva samples and reported their intensity of behavioral activation/inhibition system (BAS/BIS) and interpersonal sensitivity at either of two phases of the menstrual cycle: late follicular phase (FP), and mid-luteal phase (LP). A significant between-subject association emerged, revealing that women with higher PROG levels reported higher levels of social feedback sensitivity, and women with relatively high PROG levels showed a positive association between their E2 levels and inhibitory response. In Study 2, 30 women reported their interpersonal anxiety and finished the social value orientation (SVO) measures at both late FP and mid-LP. A significant within-person effect emerged: women in the mid-LP, which is characterized by higher PROG levels, reported higher levels of interpersonal anxiety and SVO. In sum, these findings revealed that women's social orientation could fluctuate naturally with ovarian hormones across the menstrual cycle.

A Randomized Trial of Progesterone in Women With Bleeding in Early Pregnancy

(N Engl J Med. 2019;380(19):1815–1824) This study aimed to determine whether the controversial use of progesterone therapy in women with early bleeding in pregnancy could result in a higher incidence of live births than use of a placebo. It was a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women received vaginal suppositories of progesterone, or a placebo, from presentation of bleeding to 16 weeks to determine if progesterone therapy helps improve pregnancy outcomes for women with vaginal bleeding in early pregnancy.

Progesterone for Threatened Abortion (a Commentary on a Randomized Trial of Progesterone in Women With Bleeding in Early Pregnancy

(N Engl J Med. 2019;380(19):1867–1868) Threatened abortion is a condition in which a pregnant woman experiences bleeding through the vagina and closed cervix before a fetus has reached a viable gestational age. Although most women who experience bleeding early in their pregnancies do not experience miscarriage, there remains a justifiable interest in determining treatments to improve the chances of a healthy live-born baby from such a high-risk pregnancy. The original study was to determine whether the widely accepted hormonal treatment method of progesterone effectively produces the desired live births.

A Randomized Trial of Progesterone in Women With Bleeding in Early Pregnancy

(Abstracted from N Engl J Med 2019;380:1815–1824) The hormone progesterone plays a critical role in preparing the endometrium for implantation of the embryo and continues to be produced throughout pregnancy. Historically, progesterone supplementation has been initiated during early pregnancies to prevent miscarriages in asymptomatic women who have a history of recurrent miscarriages or to rescue a pregnancy in women who have started to bleed during early pregnancy.

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy

BackgroundBleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.ResultsA total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups.ConclusionsAmong women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.)

SAT-018 Differences In Assay Results Can Be Traced To The Metabolism Of Administered Progesterone In Women Taking Progesterone Supplementation

Hormone replacement therapy (HRT) is useful in peri- and post-menopausal women to alleviate symptoms using a variety of HRT strategies to deliver estrogen either orally or transdermally and oral progesterone. However, the various assays available to measure steroid hormones have rapidly improved, evolving from antibody-based testing to highly specific tandem mass spectrometry methods. Recently, we observed mismatches in the results of anonymized patient samples submitted for progesterone measurement using immunoassays (IA) and tandem mass spectrometry (MS) methods with progesterone results being lower in the MS assays and higher in the IA measured on the same samples. We hypothesized that these differences could reflect the accumulation of progesterone metabolites in patients following the administration of supplemental oral progesterone such that the IA was unable to distinguish progesterone from its metabolites. To explore this hypothesis, we conducted a prospective observational study to examine progesterone levels in cycling premenopausal women (on no therapy, n = 2), premenopausal women (receiving oral progesterone, n = 4), and postmenopausal women (on progesterone replacement, n = 10). Women provided a baseline (8 AM) serum measurement, and +1, +2, and +4 hour samples. All subjects took their progesterone dose immediately after the baseline sample. In spontaneously cycling premenopausal women, the progesterone measurements of IA and MS (0, 1, 2 and 4 hours) were highly correlated. In all progesterone supplemented individuals, the MS baseline progesterone levels were lower than the IA values. Following administration of progesterone, progesterone levels in both methods rose, peaking at 1-2 hours after administration and then falling. The magnitude of this increase varied between methods and individuals receiving the same dose of supplemental progesterone. However, the magnitude of increase was always higher in the IA assay. MS analysis of these samples showed the presence of the progesterone metabolites, 20 alpha- and 5 alpha-dihydroprogesterone. The presence of these two metabolites and other as-yet-untested metabolites most likely explains the different progesterone values measured in the IA and MS assays in progesterone supplemented individuals. These findings reinforce the need to recognize the capabilities of the assays used and the kinetics with which administered progesterone is metabolized in order to guide patient dosing.

Progesterone and women's anxiety across the menstrual cycle

Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

BackgroundProgesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.MethodsWe conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation.ResultsA total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significant between-group differences in the rate of adverse events.ConclusionsProgesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.)

Facial coloration tracks changes in women's estradiol

Red facial coloration is an important social cue in many primate species, including humans. In such species, the vasodilatory effects of estradiol may cause red facial coloration to change systematically during females' ovarian cycle. Although increased red facial coloration during estrus has been observed in female mandrills (Mandrillus sphinx) and rhesus macaques (Macaca mulatta), evidence linking primate facial color changes directly to changes in measured estradiol is lacking. Addressing this issue, we used a longitudinal design to demonstrate that red facial coloration tracks within-subject changes in women's estradiol, but not within-subject changes in women's progesterone or estradiol-to-progesterone ratio. Moreover, the relationship between estradiol and facial redness was observed in two independent samples of women (N = 50 and N = 65). Our results suggest that changes in facial coloration may provide cues of women's fertility and present the first evidence for a direct link between estradiol and female facial redness in a primate species.

Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.

The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.

Treatment of Premenstrual Syndrome with Progesterone in Women with Polycystic Ovary Syndrome

Introduction: Premenstrual Syndrome (PMS) is defined as a group of disorders characterized by emotional and physical symptoms that occur in the luteal phase of the menstrual cycle and subside following menstruation. The reported prevalence of severe PMS is variable between 3% and 24%. Etiology of PMS remains unknown but cyclical ovarian activity and the effect of estradiol and progesterone on the neurotransmitters serotonin and gammaaminobutyric acid appear to be key factors. One hypothesis that the cause of PMS is the deficiency of progesterone and its derivatives. Polycystic Ovary Syndrome (PCOS) is characterized with chronic anovulation and oligo-ovulation. Due to this there is a distinct deficiency of progesterone and its derivatives in PCOS. The aim of this study was to investigate the efficiency of progesterone therapy for PMS in woman with PCOS. Materials and methods: A randomized double blind controlled trial was performed on 60 women with PCOS and PMS. In the study group (progesteron group = group A, n=30), progesteron in a total amount of 300 mg was prescribed for a per day basis on three times a day, and in the control group (placebo group=group B, n=30) placebo capsules, which were completely similar to progesteron capsules were prescribed from day 15 to day 25. The severity and duration of symptoms were compared in both groups before treatment and 3 months after the beginning of treatment with Visual Analog Scala (VAS). Participants were requested to answer questions about their recurrent experience of 16 symptoms during the premenstrual phase. Data were analyzed using the Statistical Package for Social Science (SPSS, version 15.0). Results: We investigated 60 females (mean age progesterone group / placebo group= 26.6 ± 2,5/ 27 ± 1,8years; range = 18-35 years). Two or more premenstrual symptoms were detected in 95.5% of the participants. The most frequent symptoms are depression, anxiety, abdominal bloating, mood swings, breast tenderness. Statistical significant decline was seen in progesterone treatment group in depression, irritablity, anxiety, mood swing, abdominal bloating, sleeplessness, felt hopeless, breast tenderness, less interest in usual activities symptoms. Conclusion: In this study comparing progesterone therapy with placebo for PMS in women with PCOS, we found that women had much lower depression, irritability, anxiety, mood swing, abdominal bloating, sleeplessness, felt hopeless, breast tenderness, less interest in usual activities symptoms during progesterone treatment.

Opioid action: Analysis of the impact of ovarian steroids on pharmacokinetics of morphine using population pharmacokinetics

Gender related differences have been documented in the analgesic effect received from morphine in both human and animal studies. Pharmacodynamic factors have been investigated to explain these differences, but pharmacokinetic factors could also differ between males and females. Morphine and steroid hormones are both metabolized by a similar pathway and different levels of steroid hormones have been shown to alter the metabolism of morphine. This study investigates the effect of covariates such as subject demographics and biochemical data, including steroid hormone level, on the pharmacokinetics of oral morphine in post-menopausal women. Plasma concentration levels of morphine were modeled using a population pharmacokinetic approach (WinNonMix, Pharsight Corp, Mountain View CA) after a standardized dose. The data was initially modeled with a one-compartment, first order pharmacokinetic model with no lag time and with no covariates. Systematically, the covariates were added to the model. Adjusting the model for the individual covariates of age or endogenous steroid levels reduced the error in the pharmacokinetic model. The covariate adjustments that provided the largest error reduction were estrogen and progesterone. The greatest error reduction was found using progesterone alone as a covariate for V/F, volume of distribution divided by bioavailability. The results showed that systemic levels of progesterone affect the pharmacokinetics of oral morphine in post-menopausal women. If this correlation applies also to the level of analgesia experienced in elderly women, dosing regimen of morphine may need to be adjusted in respect to the women's progesterone level. Supported by NIH R03AG16509-01. Gender related differences have been documented in the analgesic effect received from morphine in both human and animal studies. Pharmacodynamic factors have been investigated to explain these differences, but pharmacokinetic factors could also differ between males and females. Morphine and steroid hormones are both metabolized by a similar pathway and different levels of steroid hormones have been shown to alter the metabolism of morphine. This study investigates the effect of covariates such as subject demographics and biochemical data, including steroid hormone level, on the pharmacokinetics of oral morphine in post-menopausal women. Plasma concentration levels of morphine were modeled using a population pharmacokinetic approach (WinNonMix, Pharsight Corp, Mountain View CA) after a standardized dose. The data was initially modeled with a one-compartment, first order pharmacokinetic model with no lag time and with no covariates. Systematically, the covariates were added to the model. Adjusting the model for the individual covariates of age or endogenous steroid levels reduced the error in the pharmacokinetic model. The covariate adjustments that provided the largest error reduction were estrogen and progesterone. The greatest error reduction was found using progesterone alone as a covariate for V/F, volume of distribution divided by bioavailability. The results showed that systemic levels of progesterone affect the pharmacokinetics of oral morphine in post-menopausal women. If this correlation applies also to the level of analgesia experienced in elderly women, dosing regimen of morphine may need to be adjusted in respect to the women's progesterone level. Supported by NIH R03AG16509-01.

Th1 (IFN-γ), Th2 (IL-10) and TGF-β1 Secretion in Response to Trophoblast and Progesterone in Women with Unexplained Recurrent Pregnancy Loss and Fertile Controls

Th1 (IFN-γ), Th2 (IL-10) and TGF-β1 Secretion in Response to Trophoblast and Progesterone in Women with Unexplained Recurrent Pregnancy Loss and Fertile Controls

Resetting the thermoregulatory set-point by endogenous estradiol or progesterone in women.

Resetting the thermoregulatory set-point by endogenous estradiol or progesterone in women.

Effect of Postovulatory Treatment with a Luteinizing Hormone-Releasing Hormone Analog on the Plasma Level of Progesterone in Women

(des-Gly-NH2(10),Pro-ethylamide9) luteinizing hormone-releasing hormone (LH-RH) (100 microgram) was administered subcutaneously once daily for 5 days during the postovulatory period in six women with regular menstrual cycles. Plasma levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone were measured daily by radioimmunoassay from the ovulatory stage to menses. Suppression of plasma progesterone occurred during the treated luteal phase as compared with that of the control luteal phase. This finding suggests that repetitive, massive, endogenous luteinizing hormone or massive, exogenous, LH-RH itself during the early luteal phase of the cycle may induce functional luteolysis.

Plasma Progesterone in Women with a History of Recurrent Early Abortions

Basal body temperature, vaginal hormonocytology, and plasma progesterone concentrations were studied serially in consecutive menstrual cycles of 8 normal subjects and of 10 patients with a history of recurrent early abortions. The menstrual patterns and characteristics of basal body temperature of the patients did not differ significantly from those of control subjects. The mean plasma progesterone concentrations at the midluteal phase of the study cycles of three patients were below those of the lower limit of the control group (4 ng/ml). The results of this study support the conviction that an inadequate luteal phase is more likely to occur in women with a history of recurrent early abortions.

Luteinizing Hormone and Progesterone in Women Under Postcoital Contraception with d-Norgestrel

Luteinizing hormone (LH) and progesterone (Pg) levels in blood were measured simultaneously by radioimmunoassay during 53 menstrual cycles in order to investigate the effect of 400 μg of D -norgestrel, administered postcoitally, on pituitary and ovarian function. Of 31 control cycles, 2 appeared to be anovulatory, since the LH peak and subsequent Pg elevation were absent. Twenty-nine cycles showed typical LH surges in the middle of the cycle, followed by a manifold Pg increase. Twelve women received 5 to 13 tablets of D-norgestrel. A total absence or at least marked suppression of LH and Pg elevations was observed. In a third group, D-norgestrel was administered on scheduled days. Each woman ingested one to four tablets between the 6th and 18th days of the cycle. Two or more tablets disturbed LH and Pg ovulatory patterns. Of four women who received a tablet on day 10, one failed to show characteristic ovulatory patterns and three exhibited a delay in the time of the LH and Pg increase. These results demonstrate that D-norgestrel in a postcoital regimen alters pituitary and ovarian function, strongly suggesting an antiovulatory effect.