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  1. Wahabi HA, Fayed AA, Esmaeil SA, Bahkali KH
    Cochrane Database Syst Rev, 2018 Aug 06;8(8):CD005943.
    PMID: 30081430 DOI: 10.1002/14651858.CD005943.pub5
    BACKGROUND: Miscarriage is a common complication encountered during pregnancy. It is defined as spontaneous pregnancy loss before 20 weeks' gestation. Progesterone's physiological role is to prepare the uterus for the implantation of the embryo, enhance uterine quiescence and suppress uterine contractions, hence, it may play a role in preventing rejection of the embryo. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. This update of the Cochrane Review first published in 2007, and previously updated in 2011, investigates the evidence base for this practice.

    OBJECTIVES: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage.

    SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (8 August 2017) and reference lists of retrieved trials.

    SELECTION CRITERIA: Randomised, quasi-randomised or cluster-randomised controlled trials, that compared progestogen with placebo, no treatment or any other treatment for the treatment of threatened miscarriage in women carrying singleton pregnancy.

    DATA COLLECTION AND ANALYSIS: At least two review authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data and graded the body of evidence.

    MAIN RESULTS: We included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes.Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone.Treatment of preterm birth with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence).We are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence).

    AUTHORS' CONCLUSIONS: The results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.

    Matched MeSH terms: Progestins/adverse effects; Progestins/therapeutic use*
  2. Hawariah A, Stanslas J
    Anticancer Res, 1998 Nov-Dec;18(6A):4383-6.
    PMID: 9891496
    Previous studies have shown that a styrylpyrone derivative (SPD) from a local tropical plant had antiprogestin and antiestrogenic effects in early pregnant mice models (Azimahtol et al. 1991). Antiprogestins and antiestrogens can be exploited as a therapeutic approach to breast cancer treatment and thus the antitumor activity of SPD was tested in three different human breast cancer cell lines that is: MCF- 7, T47D and MDA-MB-231, employing, the antiproliferative assay of Lin and Hwang (1991) slightly modified. SPD (10(-10) - 10(-6) M) exhibited strong antiproliferative activity in estrogen and progestin-dependent MCF-7 cells (EC50 = 2.24 x 10(-7) M) and in hormone insensitive MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but caused only partial inhibition of the estrogen- insensitive T47D cells (EC50 = 1.58 x 10(-6) M). However, tamoxifen showed strong inhibition of MCF-7 cells (EC50 = 1.41 x 10(-6) M) and to a lesser extent the T47D cells (EC50 = 2.5 x 10(-6) M) but did not affect the MDA-MB-231 cells. SPD at 1 microM exerted a beffer antiestrogenic activity than 1 microM tamoxifen in suppressing the growth of MCF-7 cells stimulated by 1 nM estradiol. Combined treatment of both SPD and tamoxifen at 1 microM showed additional inhibition on the growth of MCF-7 cells in culture. The antiproliferative properties of SPD are effective on both receptor positive and receptor negative mammary cancer cells, and thus appear to be neither dependent on cellular receptor status nor cellular hormone responses. This enhances in vivo approaches as tumors are heterogenous masses with varying receptor status.
    Matched MeSH terms: Progestins/pharmacology
  3. Goh TH, Hariharan M
    Contraception, 1983 Oct;28(4):329-36.
    PMID: 6667621
    Blood haemoglobin and serum ferritin levels were measured at the initial visit and 12 months following sterilization and IUD insertion. Ferritin levels were unaltered in Progestasert users after 12 months but haemoglobin values increased though not significantly. Ferritin levels fell in Multiload Cu 250 users and in sterilized women; haemoglobin levels were also observed to fall but significantly only in the latter group. Iron-deficiency anaemia was prevalent at initial contact and there appeared to be an increased risk subsequently in Multiload Cu 250 users and in those who were sterilized. Screening and monitoring for anaemia is indicated. From the viewpoint of iron status, the Progestasert is preferable to the Multiload Cu 250 but it suffers the major disadvantages of needing frequent replacement and of causing menstrual disturbances which might compromise its acceptability. Menstrual blood loss studies may help explain why anaemia develops after sterilization.
    Matched MeSH terms: Progestins/administration & dosage*
  4. Othman Z, Shafin N, Zakaria R, Hussain NH, Mohammad WM
    Menopause, 2011 Nov;18(11):1219-24.
    PMID: 21926932 DOI: 10.1097/gme.0b013e31821e2044
    The aim of this study was to evaluate the verbal learning and memory performance of postmenopausal women who received tualang honey (Agro Mas) in comparison with women receiving estrogen plus progestin therapy and untreated controls.
    Matched MeSH terms: Progestins/administration & dosage; Progestins/pharmacology
  5. Tan PC, King AS, Vallikkannu N, Omar SZ
    Arch Gynecol Obstet, 2012 Mar;285(3):585-90.
    PMID: 21796421 DOI: 10.1007/s00404-011-2026-3
    To evaluate the effect of a single 250-mg dose of 17 alpha-hydroxyprogesterone caproate (17-OHPC) intramuscularly as adjunct to nifedipine tocolysis in preterm labor.
    Matched MeSH terms: Progestins/administration & dosage*; Progestins/adverse effects
  6. Shafin N, Zakaria R, Hussain NH, Othman Z
    Menopause, 2013 Jun;20(6):661-6.
    PMID: 23715378 DOI: 10.1097/GME.0b013e31827758c6
    The aim of this study was to examine the association between changes in blood oxidative stress level/activity and changes in memory performance among postmenopausal women.
    Matched MeSH terms: Progestins/administration & dosage*
  7. Pandian RU
    Maturitas, 2009 Dec;65 Suppl 1:S47-50.
    PMID: 20005647 DOI: 10.1016/j.maturitas.2009.11.016
    Threatened miscarriage is a common problem during pregnancy.
    Matched MeSH terms: Progestins/therapeutic use*
  8. Rahman RA, Atan IK, Ali A, Kalok AM, Ismail NAM, Mahdy ZA, et al.
    BMC Pregnancy Childbirth, 2021 May 10;21(1):368.
    PMID: 33971828 DOI: 10.1186/s12884-021-03838-x
    BACKGROUND: Spontaneous preterm birth is a global issue that contributed to perinatal morbidities and mortalities worldwide. The study aimed to describe the experience at UKM Medical Center in managing women at high risk for spontaneous preterm birth using the Arabin pessary.

    METHODS: This is a retrospective observational study involving 58 pregnancies from 1st January 2013 to 31st December 2019. Inclusion criteria were previous mid-trimester miscarriage and/or preterm birth, previous cervical surgery or short cervical length on routine sonogram. The demographic data, characteristics of each pregnancy and details of outcomes and management were described.

    RESULTS: The majority of women were Malay with mean age and body mass index of 32.9 ± 4.2 years and 27.1 ± 6.3 kg/m2 respectively. The most frequent indications for Arabin pessary insertion were previous mid-trimester miscarriage (46.4%) and early preterm birth (17.2%). A total of 73.4% of these women had the pessary inserted electively at a mean cervical length of 31.6 ± 9.1 mm at median gestation of 15.0 weeks. They were managed as outpatient (56.9%), inpatient (24.1%) or mixed (19.0%) with combination of progestogen (81.0%) and 53.4% received antenatal corticosteroids. Spontaneous preterm birth at or more than 34 weeks gestation occurred in 74.1% with birthweight at or more than 2000 g (82.4%). Despite cervical funneling in 12 women (20.7%), 66.7% delivered at or later than 34 weeks gestation and 2 (16.7%) resulted in miscarriage.

    CONCLUSIONS: Insertion of the Arabin pessary is beneficial to prevent spontaneous preterm birth in pregnant women who are at high risk. In particular, early insertion and close monitoring allows the best possible outcomes.

    TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov ( NCT04638023 ) on 20/11/2020.

    Matched MeSH terms: Progestins/therapeutic use*
  9. Zainul Rashid MR, Lim JF, Nawawi NH, Luqman M, Zolkeplai MF, Rangkuty HS, et al.
    Gynecol Endocrinol, 2014 Mar;30(3):217-20.
    PMID: 24552449 DOI: 10.3109/09513590.2013.860960
    Gestational hypertension (GH) remains one of the main causes of high maternal and perinatal morbidity and mortality worldwide with the highest incidence among primigravidae of about 10%-15%. However, it was noted that the incidence of GH in primigravidae who conceived following assisted reproductive technique (ART) or intrauterine insemination (IUI) supplemented with dydrogesterone during the first trimester was low.

    Study site: Obstetrics and Gynecology
    Department, Pusat Perubatan Universiti Kebangsaan Malaysia PPUKM
    Matched MeSH terms: Progestins/therapeutic use*
  10. Jaffar Ali, Hamid Arshat, Khalid Hassan, Noor Laily Abu Bakar
    Malays J Reprod Health, 1983 Jan;1(1):60-8.
    PMID: 12279891
    Matched MeSH terms: Progestins
  11. Jamaludin J, Nordin NM, Mohamad N, Etta KM
    Malays J Reprod Health, 1988 Jun;6(1):65-9.
    PMID: 12281593
    Subcutaneous body fat and Quetelet's Indices (QI) of 52, 18-29 year old normal female volunteers were determined. These body mass indices were then grouped according to the phase of each subject's menstrual cycle, early or late follicular and early or late luteal phase. The subcutaneous body fat is 27.07 +or- 1.0% in the early follicular but drops to 24.68 +or- 1.84% in the late follicular phase. The value then rises significantly higher than that in the late follicular phase to 30.14 +or- 1.15% (P0.02) in the early luteal drops to 27.17 +or- 0.55% towards the level of the early follicular phase (P0.05). Variations in the values of QI during each menstrual cycle exactly mirror those for subcutaneous body fat. The fall in the 2 body mass indices during the late follicular phase coincides somewhat with the established preovulatory LH and FSH surges as well as the high levels of estrogen of this period. On the other hand the significant rise in the 2 parameters during the early luteal phase coincides with the marked rise in the ratio of progesterone to estrogen. Clearly, increased levels of progesterone relative to estrogen appear to cause an increase in the body fat during each menstrual cycle. The implication of this finding for women on contraceptive pills which are predominantly progesterone and those whose normal menstrual cycle is "interrupted" at the early luteal phase by a successful fertilization raises very interesting questions with regards to prediction of ovulation.
    Matched MeSH terms: Progestins
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