Variations In Estradiol Levels Research Articles

O-074 Dual trigger is not superior to GnRH Agonist alone for final oocyte maturation in elective fertility preservation. A Randomized Controlled Trial

Abstract Study question Is Dual trigger for final oocyte maturation associated with a higher number of mature (MII) oocytes compared to GnRH-a trigger alone in elective fertility preservation? Summary answer Adding hCG to GnRH-a for triggering final oocyte maturation does not increase the number of MII oocytes in elective fertility preservation cycles. What is known already Triggering final oocyte maturation represents a key step in ovarian stimulation. In good prognosis patients undergoing oocyte cryopreservation, the current standard approach involves the administration of a single bolus of GnRH-agonist 36 hours before the pick-up. Previous studies have shown a higher number of MII oocytes when Dual Trigger (hCG+ GnRH-a) is performed, compared to recombinant human chorionic gonadotropin (rhCG) alone. Nevertheless, a notable gap exists in the literature, as no studies have investigated the potential additional benefit in final oocyte maturation when dual trigger is compared to GnRH-a alone. Study design, size, duration This is a randomized controlled superiority trial including elective oocyte cryopreservation cycles performed in a University Hospital. A total of 109 women were enrolled in this study between October 2021 to April 2023 with a 1:1 allocation. Eligible patients were ≤40 years old, with an antral follicular count (AFC)<20 and anti-Mullerian hormone (AMH)≤3ng/ml. Patients were randomized to final oocyte maturation triggering with Triptorelin 0,2mg or a dual trigger (Triptorelin 0.2 mg + 250 ug rhCG). Participants/materials, setting, methods Controlled ovarian stimulation was performed using 225-300IU/day of rFSH alfa or beta, or equivalent rFSH delta (15-20μg), tailored to ovarian reserve and BMI. LH surge was suppressed through a progestin-primed ovarian stimulation (PPOS) protocol, with oral administration of micronized progesterone (200mg daily) from the beginning of ovarian stimulation until the trigger day. The primary outcome was the number of MII oocytes. Comparisons are presented as estimated mean difference (EMD) and corresponding 90% confidence interval (CI). Main results and the role of chance Overall, 104 patients were analyzed, 51 in the Dual trigger group and 53 in the control arm (GnRH-a). We found no statistically significant differences in the number of retrieved oocytes comparing Dual Trigger group (8.71 ± 4.90) and GnRH-a group (9.51 ± 5.19). Similarly, the number of MII oocytes demonstrated no significant differences, with 6.86 ± 4.40 in the Dual Trigger group compared to 7.87±4.40 in the GnRH-a group (EMD -1.01 [90%CI: -2.44;0.43]). Exploring the hormonal profile there were no notable variations in estradiol levels (2064.60 ± 890.50 pg/ml vs. 2494.41 ± 1341.05 pg/ml), progesterone levels (7.78 ± 3.88 ng/ml vs. 8.94 ± 5.10 ng/ml), LH (56.28 ± 26.83 IU/L vs. 63.41 ± 32.50 IU/L), and FSH (31.14 ± 7.86 IU/L vs. 31.53 ± 9.89 IU/L) on the day following the trigger. Notably, neither group exhibited any case of Ovarian Hyperstimulation Syndrome (OHSS). Limitations, reasons for caution The sample size was calculated to detect differences on the number of MII oocytes. Therefore, results for secondary outcomes (number of oocytes retrieved and hormonal profile) should be interpreted with caution. Wider implications of the findings Adding hCG to GnRH-a for triggering final oocyte maturation does not confer any additional benefits in elective fertility preservation in term of MII oocytes compared to the administration of GnRH-a alone. Trial registration number NCT04992468

Impaired inhibition after delta-9-tetrahydrocannabinol in women not related to circulating estradiol levels

Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), impair cognitive processes, including the ability to inhibit inappropriate responses. However, responses to cannabinoid drugs vary widely, and little is known about the factors that influence the risk for adverse effects. One potential source of variation in response to cannabinoids in women is circulating ovarian hormones such as estradiol and progesterone. Whereas there is some evidence that estradiol affects responses to cannabinoids in rodents, little is known about such interactions in humans. Here, we investigate whether variations in estradiol levels across the follicular phase of the menstrual cycle modulate the effect of THC on inhibitory control in healthy women. Healthy female occasional cannabis users (N = 60) received THC (7.5 mg and 15 mg, oral) and placebo during either the early follicular phase, when estradiol levels are low, or the late follicular phase, when estradiol levels are higher. They completed a Go/No Go (GNG) task at the time of peak drug effect. We hypothesized that the effects of THC on GNG performance would be greater when estradiol levels were elevated. As expected, THC impaired GNG task performance: it increased response time and errors of commission/false alarms and decreased accuracy, relative to placebo. However, these impairments were not related to estradiol levels. These results suggest that THC-induced impairments in inhibitory control are not affected by cycle-related fluctuations in estradiol levels.

Estradiol variability is associated with brain structure in early adolescent females

One-third of adolescents are diagnosed with a psychiatric disorder by age 16, with female adolescents twice as likely to experience an internalizing (i.e., depression or anxiety) disorder as their male peers. Individual differences in pubertal factors may partially underlie this disparity, potentially via the role of pubertal hormones in shaping brain development. While research has examined links between estradiol levels and brain structure, individual variation in estradiol levels has not been considered. Using longitudinal data from 44 female adolescents (baseline age M = 11.7; follow-up age M= 13.3), we examined associations between both average estradiol and estradiol variability, and brain gray matter structure at baseline. We used a hypothesis-driven region of interest (ROI) approach focusing on subcortical and ventromedial prefrontal regions, in addition to an exploratory whole-brain analysis. We also investigated whether brain structure mediated the association between estradiol measures and internalizing (i.e., anxious and depressive) symptoms at follow-up. ROI analyses revealed a significant negative association between estradiol variability and thickness of the right medial orbitofrontal cortex (OFC, β = −0.39, FDR corrected p = .010). There were, however, no significant associations between average estradiol or estradiol variability and internalizing symptoms, nor was there evidence of mediation. Our results indicate that increased variation in estradiol levels across a month is associated with decreased cortical thickness in a brain region implicated in emotion processing, although implications for mental health are unclear. Findings, however, highlight the importance of considering individual variation in estradiol when examining links to brain development.

Determination of estradiol and progesterone content in capsules and creams from compounding pharmacies.

Objectives:To analytically characterize the doses of estradiol and progesterone found in compounded combined forms of oral capsule and transdermal cream formulations, and determine the consistency of the hormone formulations within a batch.Methods:Prescriptions for combined estradiol/progesterone capsules (0.5 and 100 mg, respectively) and creams (0.5 and 100 mg/g, respectively) were sent to 15 custom-compounding pharmacies. Estradiol and progesterone levels were measured by radioimmunoassays. Hormone levels were measured in 2 capsules and 2 creams from each pharmacy; 10 capsules from 3 pharmacies; and top/middle/bottom layer of cream containers to assess consistency. The magnitude and sources of variation for the measurements were examined by analysis of variance models.Results:Thirteen pharmacies filled the prescriptions. Measured estradiol levels were 0.365 to 0.551 mg for capsules and 0.433 to 0.55 mg/g for creams, and progesterone levels were 90.8 to 135 mg for capsules and 93 to 118 mg/g for creams. Greater variations in estradiol levels were observed between pharmacies for estradiol in capsules than in creams; however, measured estradiol levels within pharmacies were more consistent in the capsules than the creams. Similar results were obtained for progesterone levels.Conclusion:The variations in estradiol and progesterone levels observed in compounded hormone therapy formulations justify concerns regarding risks as a result of variability, which have been outlined by The North American Menopause Society, the American College of Obstetricians and Gynecologists, and the US Food and Drug Administration (FDA) in their statements regarding compounded hormone use. These data support the need for an US FDA-approved bioidentical hormone therapy.Supplemental Digital Content is available in the textVideo Summary: Supplemental Digital Content 1.

Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study

Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency.

Sex hormones modulate neurophysiological correlates of visual temporal attention

The functional cerebral asymmetry (FCA) in processing targets within rapid serial visual presentation (RSVP) streams has been reported to fluctuate across the menstrual cycle, with identification of the second of two closely spaced targets being impaired when both targets occur in the left or the right hemifield stream during the luteal phase, while during the menstrual phase identification of the second target is only impaired for target pairs presented in the right hemifield stream. This fluctuation has been proposed to result from variations in estradiol levels. The current study used EEG to investigated whether the cycle-related fluctuation in RSVP target identification FCA relates to changes in early, stimulus-driven, bottom-up or in later, top down-driven aspects of FCA. While the former would be expected to become evident in the early visual evoked potentials (VEPs) P1 or N1, the latter would be evident in later event-related potentials (ERPs) such as N2pc or P3. Women performed a dual-stream RSVP task once during the menstrual phase and once during the follicular phase. Estradiol levels were determined from saliva samples. In contrast to previous findings, FCA in RSVP target identification was not affected by cycle phase. However, the impairment in second-target identification when targets where closely spaced was generally smaller during the menstrual phase than during the follicular phase. This effect was matched by shorter peak latencies of P1 VEPs for the menstrual phase, and by a reduction in the latency of the second-target P3 ERP for closely spaced relative to widely spaced target pairs, again for the menstrual phase. Results suggest that in a dual-stream RSVP setup, target identification, early stage stimulus processing, and target consolidation are affected by cycle phase, but that the asymmetry of these effects does not differ between menstrual and follicular phase. The observed cycle-related modulations in neurophysiology and behavior could relate to the effects of estradiol on the locus ceruleus norepinephrine (LC-NE) system, which is known to play a major role in arousal, attention and stress response.

Impact of the estrus cycle and reduction in estrogen levels with aromatase inhibition, on renal function and nitric oxide activity in female rats

Estradiol increases mRNA and/or protein expression of the nitric oxide synthase (NOS) isoforms in a variety of tissues including kidney. In this study we determined the relationship between cyclical variations in estradiol levels and renal function and total NO production in the virgin female rat. In addition, we used an aromatase inhibitor (Anastrozole), to inhibit synthesis of estradiol from testosterone. Estradiol levels were higher in proestrus vs. diestrus, and were markedly suppressed by 7 days treatment with aromatase inhibitor. There was no difference in total NO production (from urinary and plasma nitrate + nitrite = NO X) between proestrus and diestrus but aromatase inhibition resulted in increases in total NO production. The renal cortical NOS activity and protein abundance also increased in aromatase-inhibited female rats. There were no differences in blood pressure (BP) in any group but the renal vascular resistance (RVR) was low in proestrus, increased in diestrus and did not change further after aromatase inhibition. In summary, the cyclical changes in renal function correlate with estradiol but not NO levels. Pharmacologic castration with aromatase inhibition leads to a marked increase in total and renal NOS. This contrasts to earlier work where surgical castration causes decreased NOS.

Habitual physical activity and estradiol levels in women of reproductive age

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

Diurnal growth hormone responses to dextroamphetamine in normal young men and postmenopausal women

(1) D-amphetamine stimulates growth hormone (GH) secretion, probably through its catecholaminergic effects. (2) In normal post-menopausal women we found the GH response to dextroamphetamine to be small and significantly less than that seen in young normal men. (3) In post-menopausal women but not in young men, the GH response to amphetamine was significantly higher in the evening than in the morning. (4) The reduced GH responses to dextroamphetamine in postmenopausal women may be due to sex difference, hypoestrogenism, or to reduced brain catecholamines associated with age. (5) The diurnal variation of the GH response to d-amphetamine in post-menopausal women may reflect a diurnal variation in hypothalamic nor-adrenergic activity higher in the evening, which was not masked by a reciprocal variation in estradiol levels.