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Global Health, Science and Practice Apr 2024Couple-years of protection (CYP) is an indicator that allows for monitoring and evaluating of family planning (FP) program performance through simple calculations. The... (Review)
Review
BACKGROUND
Couple-years of protection (CYP) is an indicator that allows for monitoring and evaluating of family planning (FP) program performance through simple calculations. The CYP for each contraceptive method is calculated by multiplying the number of contraceptive commodity units distributed to clients over a 1-year period by a conversion factor that quantifies the duration of contraceptive protection provided per unit distributed. CYP calculations across methods were previously updated in 2000 and 2011, resulting in changes in methodology, factor inclusion, and specific methods. Since the 2011 update, changes and additions to the modern contraceptive method mix required new CYP conversion factors for 4 methods of contraception: Levoplant implant, progestin-only pills (POPs), Caya diaphragm, and the hormonal intrauterine device.
METHODS
We conducted literature reviews of both published and gray literature and consulted with experts to identify updated data on continuation rates, duration of efficacy, and method effectiveness for the 4 methods. New CYP conversion factors were calculated for the 4 methods either by using the same calculation used previously for the method considering new data or, for new methods, using calculations for similar methods.
RESULTS
New CYP conversion factors were assigned to the 4 methods of contraception covered in this update: Levoplant, 2.5 CYP per implant inserted; POPs, 0.0833 CYP per pack (i.e., 12 cycles per CYP); Caya diaphragm, 1 CYP per device, and hormonal intrauterine device, 4.8 CYP per device inserted.
CONCLUSIONS
CYP is an important indicator for FP programs. As new methods of contraception are developed and new evidence is generated for current methods, the indicator may need to be updated. A standard process for updating and documenting future CYP updates is recommended.
Topics: Humans; Female; Contraception; Family Planning Services; Intrauterine Devices
PubMed: 38589048
DOI: 10.9745/GHSP-D-23-00388 -
Advanced Science (Weinheim,... Jun 2024The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond...
The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin-refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38-dependent IDH1 Thr 77 phosphorylation (pT77-IDH1). pT77-IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1-produced α-ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38-dependent pT77-IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy.
Topics: Female; Humans; Endometrial Neoplasms; Progestins; Drug Resistance, Neoplasm; Mice; Isocitrate Dehydrogenase; Animals; Phosphorylation; Cell Line, Tumor; Disease Models, Animal
PubMed: 38582508
DOI: 10.1002/advs.202310208 -
Reproductive Biology Jun 2024Women may be more susceptible to infections in the luteal phase, supposedly as a consequence of the hormone progesterone and its immunosuppressive action. While...
Women may be more susceptible to infections in the luteal phase, supposedly as a consequence of the hormone progesterone and its immunosuppressive action. While immunosuppression may be important for successful oocyte implantation and pregnancy, it makes women more vulnerable to pathogens. According to theory, to compensate for reduced immunocompetence, women in the luteal phase exhibit proactive behavioral responses, such as disgust and avoidance of disease-associated stimuli, to minimize contagion risk. However, previous studies yielded inconsistent results, and did not account for accompanying proactive immune responses, like the increase of secretory immunoglobin A (sIgA). Here, we assessed the proactive immune response and feelings of disgust associated with disease cues in the comparison of 61 woman with a natural menstrual cycle (31 in the follicular and 30 in the luteal phase) and 20 women taking hormonal contraception (HC). Women rated disease vulnerability and disgust propensity, watched a video displaying people with respiratory symptoms, which was evaluated for its disgust-evoking potential and contagiousness, and provided saliva samples for hormone and sIgA analysis. Women with HC reported a heightened vulnerability to disease compared to naturally cycling women, whereas both the feeling of disgust and the sIgA increase elicited by the disease video were similar across groups, regardless of progesterone. We found a u-shaped relationship between progesterone and baseline sIgA in naturally cycling women, with its nadir during ovulation. Overall, our data do not support a compensatory relationship between the proposed progesterone-induced immunosuppression and heightened disgust or a proactive sIgA response.
Topics: Humans; Female; Adult; Progesterone; Young Adult; Saliva; Immunoglobulin A, Secretory; Luteal Phase; Menstrual Cycle; Disgust
PubMed: 38581902
DOI: 10.1016/j.repbio.2024.100880 -
Toxicology and Applied Pharmacology May 2024Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line...
BACKGROUND
Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues.
METHODS
Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA.
RESULTS
Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands.
CONCLUSION
These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.
Topics: Animals; Female; Topiramate; Rats, Sprague-Dawley; Acetazolamide; Endocrine Disruptors; Rats; Estrus; Luteinizing Hormone; Fructose; Pituitary Gland; Progesterone; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Estradiol; Ovary
PubMed: 38580201
DOI: 10.1016/j.taap.2024.116919 -
Frontiers in Endocrinology 2024Progesterone-primed cycles effectively suppress the pituitary LH surge during ovarian stimulation in oocyte donors and in the infertile population. Particularly in...
Micronized natural progesterone (Seidigestan) vs GnRH antagonists for preventing the LH surge during controlled ovarian stimulation (PRO_NAT study): study protocol of a randomized clinical trial.
INTRODUCTION
Progesterone-primed cycles effectively suppress the pituitary LH surge during ovarian stimulation in oocyte donors and in the infertile population. Particularly in oocyte donors, the use of synthetic progesterone (progestins) has been explored in prospective clinical trials, showing mixed results. This trial was designed to determine whether the use of micronized natural progesterone is as effective as the GnRH-antagonist protocol in terms of the number of mature oocytes (MII) retrieved in oocyte donation cycles as a primary outcome, and it also aims to explore the corresponding results in recipients as a secondary outcome.
METHODS
We propose a prospective, open-label, non-inferiority clinical trial to compare a novel approach for oocyte donors with a control group, which follows the standard ovarian stimulation protocol used in our institution. A total of 150 donors (75 in each group) will be recruited and randomized using a computer algorithm. After obtaining informed consent, participants will be randomly assigned to one of two ovarian stimulation protocols: either the standard GnRH antagonist or the oral micronized natural progesterone protocol. Both groups will receive recombinant gonadotropins tailored to their antral follicle count and prior donation experiences, if any. The primary outcome is the number of mature metaphase II (MII) oocytes. Secondary measures include treatment duration, pregnancy outcomes in recipients, as well as the economic cost per MII oocyte obtained in each treatment regimen. Analyses for the primary outcome will be conducted in both the intention-to-treat (ITT) and per-protocol (PP) populations. Each donor can participate only once during the recruitment period. The estimated duration of the study is six months for the primary outcome and 15 months for the secondary outcomes.
DISCUSSION
The outcomes of this trial have the potential to inform evidence-based adjustments in the management of ovarian stimulation protocols for oocyte donors.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier, NCT05954962.
Topics: Female; Humans; Pregnancy; Gonadotropin-Releasing Hormone; Hormone Antagonists; Ovulation Induction; Progesterone; Progestins; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 38577571
DOI: 10.3389/fendo.2024.1350154 -
Clinical Obstetrics and Gynecology Jun 2024The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk... (Review)
Review
The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.
Topics: Humans; Female; Pregnancy; Progesterone; Premature Birth; Administration, Intravaginal; Cervix Uteri; Progestins; Randomized Controlled Trials as Topic; Cervical Length Measurement; Infant, Newborn; Respiratory Distress Syndrome, Newborn
PubMed: 38576410
DOI: 10.1097/GRF.0000000000000867 -
Reproductive Biology and Endocrinology... Apr 2024The present study aimed to examine the effects of progranulin and omentin on basic ovarian cell functions. For this purpose, we investigated the effects of the addition...
The present study aimed to examine the effects of progranulin and omentin on basic ovarian cell functions. For this purpose, we investigated the effects of the addition of progranulin and omentin (0, 0.1, 1, or 10 ng/ml) on the viability, proliferation, apoptosis and steroidogenesis of cultured rabbit ovarian granulosa cells. To determine the importance of the interrelationships between granulosa cells and theca cells, we compared the influence of progranulin and omentin on progesterone and estradiol release in cultured granulosa cells and ovarian fragments containing both granulosa cells and theca cells. Cell viability, proliferation, cytoplasmic apoptosis and release of progesterone and estradiol were measured by Cell Counting Kit-8 (CCK-8), BrdU incorporation, cell death detection, and ELISA. Both progranulin and omentin increased granulosa cell viability and proliferation and decreased apoptosis. Progranulin increased progesterone release by granulosa cells but reduced progesterone output by ovarian fragments. Progranulin decreased estradiol release by granulosa cells but increased it in ovarian fragments. Omentin reduced progesterone release in both models. Omentin reduced estradiol release by granulosa cells but promoted this release in ovarian fragments. The present observations are the first to demonstrate that progranulin and omentin can be direct regulators of basic ovarian cell functions. Furthermore, the differences in the effects of these adipokines on steroidogenesis via granulosa and ovarian fragments indicate that these peptides could target both granulosa and theca cells.
Topics: Female; Animals; Rabbits; Progesterone; Progranulins; Adipokines; Ovary; Granulosa Cells; Estradiol; Apoptosis; Cells, Cultured; Cell Proliferation
PubMed: 38575956
DOI: 10.1186/s12958-024-01215-9 -
PloS One 2024Sex steroid hormones are important not only for reproduction but also for many aspects of women's health, including the risk of breast cancer. Physical activity has been...
OBJECTIVES
Sex steroid hormones are important not only for reproduction but also for many aspects of women's health, including the risk of breast cancer. Physical activity has been shown to influence sex hormone levels in women. This study aimed to investigate a relationship between the average daily number of steps and the sex hormone (estradiol and progesterone) levels in premenopausal women.
MATERIALS AND METHODS
Data were collected from 85 healthy, urban women of reproductive age who performed at least 180 minutes/week of moderate physical activity for two complete menstrual cycles. Physical activity was measured using wrist bands. Estradiol and progesterone concentrations were measured in daily-collected saliva samples in the second menstrual cycle.
RESULTS
There was a significant negative association between the average number of steps taken daily and salivary progesterone levels after adjusting for potential confounding factors (age, BMI). Women who took more than 10,000 steps a day had significantly lower progesterone levels compared to women who took less than 10,000 steps. The association between physical activity and estradiol levels was statistically insignificant.
DISCUSSION
Our results indicate that taking at least 10,000 steps a day reduces progesterone levels, but this intensity of physical activity may not be high enough to affect estradiol levels. Daily step tracking is a valuable element of health promotion, but currently recommended levels of physical activity may not be high enough for healthy premenopausal women to significantly reduce both sex hormone levels and thus their risk of postmenopausal breast cancer.
Topics: Female; Humans; Progesterone; Gonadal Steroid Hormones; Estradiol; Breast Neoplasms; Menstrual Cycle
PubMed: 38573970
DOI: 10.1371/journal.pone.0299580 -
The Journal of Maternal-fetal &... Dec 2024To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage.
METHODS
A randomized, controlled trial study was conducted among pregnant Thai women at the gestational age of six to less than 20 weeks who visited King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand with threatened miscarriage from August 2021 to August 2022. These pregnant women were randomized to receive oral dydrogesterone 20 mg per day or placebo twice a day until one week after vaginal bleeding stopped or otherwise for a maximum of six weeks.
RESULTS
A total of 100 pregnancies were recruited. Fifty of them were assigned to receive oral dydrogesterone and 50 were assigned to receive placebo. The rate of continuing pregnancy beyond 20 weeks of gestational age was 90.0% (45 out of 50 women) in the dydrogesterone group and 86.0% (43 out of 50 women) in the placebo group ( = 0.538). The incidence of adverse events did not differ significantly between the groups.
CONCLUSION
Oral dydrogesterone 20 mg/day could not prevent miscarriages in women with threatened miscarriage.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Abortion, Threatened; Double-Blind Method; Dydrogesterone; Progestins; Thailand
PubMed: 38570191
DOI: 10.1080/14767058.2024.2333929