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European Journal of Obstetrics,... Jun 2022To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments.
METHODS
Medline and Embase databases were searched. Inclusion criteria were studies reporting the pregnancy outcomes of women who had undergone fertility-sparing treatments for endometrial hyperplasia or early endometrioid endometrial cancer. Outcomes explored were pregnancy, miscarriage and livebirth rates according to the type of progestin treatment used. Subgroup analyses according to the type of diagnostic follow-up were also performed. Meta-analyses of proportions using a random effects model were used to combine data.
RESULTS
Twenty-nine studies (1036 women) were included, and 82.8% [95% confidence interval (CI) 72.3-91.2] of women achieved complete remission. Pregnancy rates were 56.3% (95% CI 41.6-70.5) with megestrol (MA) or medroxyprogesterone acetate (MPA), 63.1% (95% CI 37.0-85.6) with levonorgestrel-releasing intrauterine device (LNG-IUD), 57.9% (95% CI 37.7-76.8) with MA or MPA and metformin, 59.8% (95% CI 48.3-70.7) with MPA and LNG-IUD, 15.4% (95% CI 4.3-42.2) with gonadotropin-releasing hormone analogue (GnRHa) combined with LNG-IUD or letrozole, and 40.7% (95% CI 24.5-59.3) with LNG-IUD and GnRHa. Miscarriage rates were 17.4% (95% CI 12.2-23.4), 14.3% (95% CI 6.4-24.7), 57.9% (95% CI 37.7-76.8), 26.9% (95% CI 14.6-39.3), 100% (95% CI 34.0-100) and 18.2% (95% CI 5.1-47.7), respectively, and livebirth rates were 68.8% (95% CI 56.0-80.3), 80.8% (95% CI 69.5-90.0), 69.9% (95% CI 56.1-82.0), 25.97 (95% CI 14.6-39.3), 0% (95% CI 0-66.0) and 81.8% (95% CI 52.3-94.8), respectively. Finally, stratifying the analysis considering the endometrial sampling method alone, the pregnancy rate was 68.6% (95% CI 51.2-83.6; 10 studies, I = 83.5%) in women who underwent hysteroscopy and 60.5% (95% CI 53.4-67.5; 13 studies, I = 39.8%) in women managed with dilatation and curettage biopsy; the miscarriage and livebirth rates were 13.2% (95% CI 8.0-19.5; I = 0%) and 81.2% (95% CI 67.4-91.8; I = 67.3%), respectively, for hysteroscopy, and 25.2% (95% CI 17.8-33.3; I = 15.5%) and 67.5% (95% CI 58.8-75.5; I = 0%), respectively, for dilatation and curettage biopsy.
CONCLUSION
Fertility-sparing treatment in women with endometrial cancer or hyperplasia is associated with an overall good response to therapy, good chance of achieving pregnancy and a good livebirth rate. Diagnostic follow-up with hysteroscopy was associated with a higher pregnancy rate, although this requires confirmation in adequately powered randomized trials.
Topics: Abortion, Spontaneous; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hyperplasia; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Precancerous Conditions; Pregnancy; Pregnancy Outcome
PubMed: 35526471
DOI: 10.1016/j.ejogrb.2022.04.019 -
Menopause (New York, N.Y.) May 2022Long-term sleep disturbances in menopausal women are closely related to cardiovascular disorders, metabolic disorders, and cognitive impairment. At present, hormone... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Long-term sleep disturbances in menopausal women are closely related to cardiovascular disorders, metabolic disorders, and cognitive impairment. At present, hormone therapy (HT) is a standard treatment for menopausal symptoms. However, it remains unclear whether HT can improve sleep quality.
OBJECTIVE
We did a systematic review and meta-analysis to assess the effects of different HT regimens on menopausal sleep quality.
EVIDENCE REVIEW
We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and Web of Science for randomized controlled trials of menopausal HT on sleep disturbances up to June 14,2021. Information about ongoing and unpublished trials was collected by searching WHOICTRP and ClinicalTrials.gov. Our primary outcome was sleep quality with objective measurements. We estimated the standardized mean difference (SMD) using random-effects models.
FINDINGS
We identified a total of 3,059 studies and finally included 15 studies in the meta-analysis. Compared with placebo, HT improved self-reported sleep outcomes (SMD = -0.13; 95% CI, -0.18 to -0.08, P < 0.00001 and I2 = 41%), but not sleep parameters measured by polysomnography. Subgroup analyses according to the regimen of HT showed that 17β-estradiol (17β-E2) (SMD = -0.34; 95% CI, -0.51 to -0.17, P < 0.0001, and I2 = 0%) and conjugated equine estrogens (SMD = -0.10; 95% CI, -0.12 to -0.07, P < 0.00001, and I2 = 0%) improved sleep quality. Moreover, transdermal administration (SMD = -0.35; 95% CI, -0.64 to -0.06, and P = 0.02) was more beneficial than oral (SMD = -0.10; 95% CI, -0.14 to -0.07, and P < 0.00001). In addition, the combination of estrogen and progesterone had a positive effect on sleep disturbance (SMD = -0.10; 95% CI, -0.13 to -0.07, P < 0.00001, and I2 = 0%), while estrogen monotherapy did not. The results showed that estrogen/micronized progesterone (SMD = -0.22; 95% CI, -0.37 to -0.06, P = 0.007, and I2 = 0%) and estrogen/medroxyprogesterone acetate (SMD = -0.10; 95% CI, -0.13 to -0.07, P < 0.00001, and I2 = 0%) could alleviate sleep disturbance.
CONCLUSIONS AND RELEVANCE
HT has a beneficial effect on sleep disturbance to some extent, and the formulations and routes of administration of hormonal agents influence the effect size.
Topics: Estrogens; Female; Hormone Replacement Therapy; Humans; Menopause; Progesterone; Sleep Quality
PubMed: 35102100
DOI: 10.1097/GME.0000000000001945 -
Current Medical Research and Opinion Mar 2022The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms...
OBJECTIVE
The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms and quality of life.
METHODS
A literature search of PubMed, Ovid (MEDLINE and EMBASE), and Web of Science was performed from inception to December 2020. In addition, a targeted search of cited references was also performed. Our search identified 330 articles of which 17 were deemed eligible for full-text review. Eligible studies included randomized control trials, observational studies, and case series with at least 5 cases, investigating the effect of progestin subdermal implants on endometriosis-related pain scores in women of reproductive age with a clinical, radiologic, or surgical diagnosis of endometriosis. Six articles were excluded after the full-text screen.
RESULTS
Eleven articles describing a total of 335 patients were eligible for inclusion. Across all studies, etonogestrel- and segesterone-releasing progestin subdermal implants improved VAS pain scores for cyclic pelvic pain/dysmenorrhea (VAS at baseline ranged from 6.1 to 7.5 cm and after treatment from 1.7 to 4.9 cm, = 121), non-cyclic pelvic pain (baseline VAS 7.2-7.6 cm and after treatment 2.0-3.7 cm, = 96) and dyspareunia (baseline VAS 1.61-8.3 cm and after treatment 1.0-7.1 cm, = 87). Symptom improvement with the progestin subdermal implant was equivalent to treatment with depot medroxyprogesterone acetate (DMPA; average baseline VAS 6.5 and after DMPA treatment 3.0, compared to 2.0 after treatment with the implant) or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS; baseline cyclic and non-cyclic pain scores 7.3 and 7.4 respectively decreased to 1.9 and 1.9 after LNG-IUS treatment). Improvements were also demonstrated in quality-of-life scores (average improvement of 36% in all domains of the Endometriosis Health Profile-30 and significant improvements in social functioning, general health, bodily pain, vitality and mental health domains on the Short Form-36 questionnaire) and sexual function (total sexual function score improved from 24 to 25.35 and 26.25 at 6 and 12 months).
CONCLUSION
Etonogestrel- and segesterone-releasing progestin subdermal implants appear to improve endometriosis-related pain symptoms and quality of life and may provide an additional component in the management of endometriosis. However, this systematic review is limited by the small sample size and heterogeneity in the data. As such, larger prospective randomized trials are needed to guide further management.
PROSPERO REGISTRATION
CRD42021225665.
Topics: Endometriosis; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pelvic Pain; Progestins; Prospective Studies; Quality of Life
PubMed: 35048754
DOI: 10.1080/03007995.2022.2031144 -
Frontiers in Cellular and Infection... 2021Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms,...
BACKGROUND
Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO: CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods.
METHODS
Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive.
RESULTS
We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli.
CONCLUSION
Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.
Topics: Female; Humans; Lactobacillus; Microbiota; Vagina
PubMed: 34869054
DOI: 10.3389/fcimb.2021.732423 -
BMC Women's Health Oct 2021Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use.
METHODS
We searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes.
RESULTS
We identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10-1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider).
CONCLUSIONS
Self-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.
Topics: Community Health Workers; Contraceptive Agents, Female; Female; Humans; Injections; Medroxyprogesterone Acetate; Self Administration
PubMed: 34627229
DOI: 10.1186/s12905-021-01495-y -
Journal of Gynecology Obstetrics and... Sep 2021To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in patients with poor ovarian response and to find an optimal ovulation induction protocol for such patients.
METHOD
A literature search of PubMed, Medline, EBSCO, Cochrane Library, Vip.com, CNKI, and the Wanfang database was conducted to find case-control studies of PPOS with medroxyprogesterone acetate and other traditional stimulation regimens for ovulation induction in patients with poor ovarian response. The period of time searched was from the database establishment to August 2020. Patients in the experimental group underwent PPOS and those in the control group underwent another program (e.g., the gonadotropin-releasing hormone antagonist protocol). RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of sixteen case-control studies (one of them is randomized controlled trial), with 4422 induction cycles, were included. All the included patients met the 2011 Bologna diagnostic criteria for poor ovarian response. The numbers of mature eggs, available embryos, optimal embryos, and the rate of cumulative pregnancies in the PPOS group were all better than those in the control group (P<0.05). There was a lower Serum luteinizing hormone on the day of human chorionic gonadotropin (HCG) injection and a lower rate of cycle cancellation in the PPOS group (P<0.05). No other differences between PPOS and other treatments were statistically significant.
CONCLUSION
PPOS can reduce the need for cycle cancellation, improve the follicles and embryos, and improve the pregnancy rate and thus, can present an effective choice for IVF/ICSI-ET in patients with poor ovarian response.
Topics: Adult; Case-Control Studies; Contraceptive Agents, Hormonal; Female; Humans; Medroxyprogesterone Acetate; Ovary; Ovulation Induction; Treatment Outcome
PubMed: 33387677
DOI: 10.1016/j.jogoh.2020.102049 -
BMJ Supportive & Palliative Care Mar 2021Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy... (Meta-Analysis)
Meta-Analysis
AIMS
Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.
METHODS
PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.
RESULTS
80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.
CONCLUSIONS
Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.
Topics: Adrenal Cortex Hormones; Androgens; Appetite; Appetite Stimulants; Cachexia; Comparative Effectiveness Research; Drug Therapy, Combination; Gastrointestinal Agents; Ghrelin; Humans; Medroxyprogesterone; Megestrol Acetate; Minimal Clinically Important Difference; Neoplasms; Network Meta-Analysis; Randomized Controlled Trials as Topic; Terminal Care; Weight Gain
PubMed: 33246937
DOI: 10.1136/bmjspcare-2020-002601 -
The Cochrane Database of Systematic... Nov 2020Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013.
OBJECTIVES
To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials.
SELECTION CRITERIA
All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size.
AUTHORS' CONCLUSIONS
Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.
Topics: Adult; Antineoplastic Agents, Hormonal; Bias; Contraceptives, Oral; Desogestrel; Female; Goserelin; Humans; Intrauterine Devices, Medicated; Leiomyoma; Leuprolide; Levonorgestrel; Lynestrenol; Medroxyprogesterone Acetate; Menstruation; Middle Aged; Nandrolone; Norethindrone Acetate; Premenopause; Progestins; Randomized Controlled Trials as Topic; Tumor Burden; Uterine Neoplasms
PubMed: 33226133
DOI: 10.1002/14651858.CD008994.pub3 -
Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review.Menopause (New York, N.Y.) Nov 2020Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in...
IMPORTANCE
Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in combination with estrogen therapy. Although monotherapy with progestins has been used as treatment of menopausal symptoms in women with contraindications to estrogens, the optimal route, and dosage of progestin monotherapy has not been established.
OBJECTIVE
To assess whether progestin as a standalone treatment is effective for treating vasomotor and mood symptoms associated with menopause.
EVIDENCE REVIEW
We conducted a systematic review using PubMed and Embase databases from January 1980 to January 2020. We included randomized controlled trials (RCTs) that investigated different forms of progestin for the treatment of vasomotor or mood symptoms associated with menopause.
FINDINGS
A systematic search of 892 studies identified seven RCTs involving a total of 601 patients. The available literature was heterogeneous in terms of formulation and dose of progesterone; administration ranged from 5 to 60 mg of transdermal progesterone, 10 to 20 mg oral medroxyprogesterone acetate, and 300 mg of oral micronized progesterone. Duration of treatment also differed between studies, ranging from 21 days to 12 months (median: 12 wks). Three of seven RCTs reported that progestin therapy led to an improvement of vasomotor symptoms (VMS) in postmenopausal women. The largest study administering oral progestin using 300 mg micronized progesterone reported a 58.9% improvement in VMS (vs 23.5% in placebo group, n = 133), whereas the largest study using transdermal progesterone reported no improvement (n = 230). No study reported an improvement of mood symptoms. Side effects, such as headaches and vaginal bleeding, were significant in five of seven RCTs and led to discontinuation of treatment in 6% to 21% of patients.
CONCLUSIONS AND RELEVANCE
A beneficial effect was reported in some trials with the transdermal route at longer duration and with oral treatment at higher doses for VMS for progesterone-only therapy. This report may help to inform future studies of progestin-only therapy for the treatment of menopausal symptoms.
Topics: Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Menopause; Progestins
PubMed: 33109992
DOI: 10.1097/GME.0000000000001676 -
Human Reproduction Update Jan 2021Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression.
OBJECTIVE AND RATIONALE
This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified.
SEARCH METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included.
OUTCOMES
Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = -648, 95% CI = -746 to -550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET.
WIDER IMPLICATIONS
Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles.
Topics: Female; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Pregnancy; Pregnancy Rate; Progestins; Reproductive Techniques, Assisted
PubMed: 33016316
DOI: 10.1093/humupd/dmaa040