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Nature Communications Jun 2024Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to...
Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.
Topics: Humans; Female; Pregnancy; China; Maternal Exposure; Adult; Premature Birth; Pregnancy Trimester, First; Prospective Studies; Pregnancy Outcome; Dydrogesterone; Progesterone; Birth Cohort; Infant, Newborn; Abortion, Spontaneous; Stillbirth; Infant, Low Birth Weight; Longitudinal Studies; Incidence; Young Adult
PubMed: 38906856
DOI: 10.1038/s41467-024-49623-0 -
Frontiers in Endocrinology 2024To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives...
INTRODUCTION
To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction.
METHODS
Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test.
RESULTS
Following levonorgestrel gavage, serum free T and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (=0.013 and 0.043). After desogestrel gavage, the serum free T and free T levels were lower in the experimental group than that in the control group (=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid.
DISCUSSION
Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.
Topics: Animals; Female; Rats, Wistar; Rats; Progestins; Thyroid Gland; Levonorgestrel; Desogestrel; Thyroxine; Thyroid Hormones; Thyroid Function Tests
PubMed: 38904035
DOI: 10.3389/fendo.2024.1362774 -
Scientific Reports Jun 2024We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl... (Randomized Controlled Trial)
Randomized Controlled Trial
We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .
Topics: Humans; Female; Adult; Ethinyl Estradiol; Androstenes; Young Adult; Adolescent; Contraceptives, Oral, Combined; Ovulation Inhibition; Single-Blind Method; Middle Aged; Norpregnenes; Ovulation; Cervix Mucus
PubMed: 38898193
DOI: 10.1038/s41598-024-64753-7 -
BMC Women's Health Jun 2024The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females.
OBJECTIVE
To determine the effects of exercise on sex steroid hormones in eumenorrheic females.
METHODS
This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone.
RESULTS
Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I = 94%)].
CONCLUSION
A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals.
TRIAL REGISTRATION NUMBER
The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.
Topics: Humans; Female; Progesterone; Exercise; Testosterone; Estrogens; Gonadal Steroid Hormones; Randomized Controlled Trials as Topic; Estradiol
PubMed: 38890710
DOI: 10.1186/s12905-024-03203-y -
Journal of the Endocrine Society May 2024Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal...
CONTEXT
Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal contraception has on telomere length, a marker of the risk for complications.
OBJECTIVE
To investigate the relative telomere length (RTL) in AYA with T1D (AYA-T1D) and healthy young women (AYA-C) after 18 months of combined oral contraception use (COC) with ethinyl estradiol/desogestrel, or a subdermal etonogestrel implant (IM).
METHODS
A nonrandomized prospective study was performed in which 39 AYA-T1D and 40 AYA-C chose the COC or the IM. RTL was measured by monochrome multiplex-quantitative PCR in DNA from peripheral blood mononuclear cells (PBMC). The impact of contraceptives and clinical variables on RTL was assessed using lineal regression analysis.
RESULTS
Longer RTL compared to baseline was observed in AYA-T1D ( < .05) and AYA-C ( .01) after using the IM. However, the total of AYA and the AYA-C group treated with COC decreased RTL after 18 months of treatment compared to baseline ( < .05). The type of contraceptive used was determinant for the changes in RTL compared to baseline in all subjects and controls (006). For AYA-T1D, HbA1c levels were not associated with RTL, but the high-sensitivity C-reactive protein was negatively related with the changes in RTL at 18 months compared to baseline (standardized : 0.230, .003).
CONCLUSION
IM was associated with longer RTL in AYA-T1D and AYA-C. In contrast, a shortening of telomere length in PBMC was observed after using COC.
PubMed: 38883396
DOI: 10.1210/jendso/bvae091 -
European Journal of Sport Science Jun 2024We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and...
We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid-thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = -0.44 to -0.50, p < 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = -0.45 to -0.64, p < 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify "phase-based testing"; however, kinetic or kinematic outputs may be altered in NM athletes.
PubMed: 38877892
DOI: 10.1002/ejsc.12151 -
BMC Pregnancy and Childbirth Jun 2024The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent...
Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment.
OBJECTIVE
The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model.
METHODS
Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing.
RESULTS
Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed.
CONCLUSION
Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth.
Topics: Female; Pregnancy; Progesterone; Dysbiosis; Vagina; Placenta; Mice; Humans; Animals; Uterus; Microbiota; Premature Birth; Disease Models, Animal; Progestins
PubMed: 38877443
DOI: 10.1186/s12884-024-06595-9