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Best Practice & Research. Clinical... Nov 2020This chapter explores the role of progesterone and progestogens in the management of abnormal uterine bleeding (AUB). Progestogens are used to regulate intermenstrual... (Review)
Review
This chapter explores the role of progesterone and progestogens in the management of abnormal uterine bleeding (AUB). Progestogens are used to regulate intermenstrual bleeding and decrease heavy menstrual bleeding (HMB) in women of reproductive age or who are perimenopausal. In menopausal women, progesterones and progestogens prevent endometrial hyperplasia and aim to reduce the development of endometrial cancer. We hope to make clear current best practice including preparation, specific benefits and risks. Progesterone also acts in concert with other hormones to affect breast, cardiovascular system, lipid profile and bone. We hope to explain how its unintended side effects may be used beneficially or may cause intended side effects.
Topics: Female; Humans; Menorrhagia; Metrorrhagia; Progesterone; Progestins; Uterine Hemorrhage
PubMed: 32698992
DOI: 10.1016/j.bpobgyn.2020.05.004 -
Frontiers in Neuroendocrinology Oct 2020Estradiol is the "prototypic" sex hormone of women. Yet, women have another sex hormone, which is often disregarded: Progesterone. The goal of this article is to provide... (Review)
Review
Estradiol is the "prototypic" sex hormone of women. Yet, women have another sex hormone, which is often disregarded: Progesterone. The goal of this article is to provide a comprehensive review on progesterone, and its metabolite allopregnanolone, emphasizing three key areas: biological properties, main functions, and effects on mood in women. Recent years of intensive research on progesterone and allopregnanolone have paved the way for new treatment of postpartum depression. However, treatment for premenstrual syndrome and premenstrual dysphoric disorder as well as contraception that women can use without risking mental health problems are still needed. As far as progesterone is concerned, we might be dealing with a two-edged sword: while its metabolite allopregnanolone has been proven useful for treatment of PPD, it may trigger negative symptoms in women with PMS and PMDD. Overall, our current knowledge on the beneficial and harmful effects of progesterone is limited and further research is imperative.
Topics: Emotions; Female; Humans; Pregnanolone; Premenstrual Dysphoric Disorder; Progesterone
PubMed: 32730861
DOI: 10.1016/j.yfrne.2020.100856 -
The Journal of Allergy and Clinical... Dec 2023Progestogen hypersensitivity (PH) is a heterogeneous disease characterized by diverse cutaneous manifestations, bronchospasm, and/or anaphylaxis. Possible triggers...
Progestogen hypersensitivity (PH) is a heterogeneous disease characterized by diverse cutaneous manifestations, bronchospasm, and/or anaphylaxis. Possible triggers include ovarian progesterone and exogenous progestogens. The timing of symptoms is critical to diagnose PH: during the luteal phase of the menstrual cycle for the endogenous form and after exposure to progestins for exogenous PH. Diagnostic modalities such as progesterone skin testing have low sensitivity and specificity for PH. When exogenous PH is suspected, the allergist should consider a progestogen challenge. Treatment strategies should be tailored for each patient, including symptom-directed therapies, ovulation suppression, and progesterone desensitization. Future studies should explore the mechanisms of PH, validation of diagnostic criteria, and standardization of treatment strategies.
Topics: Female; Humans; Progestins; Progesterone; Desensitization, Immunologic; Anaphylaxis; Menstrual Cycle
PubMed: 37579875
DOI: 10.1016/j.jaip.2023.07.050 -
Pathology Oncology Research : POR Jan 2020Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as... (Review)
Review
Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed againts the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: 'HRT is advanageous' (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); 'HRT is neutral' (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); 'HRT is relatively contraindicated' for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); 'HRT is diasadvantageous and thus contraindicated' (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).
Topics: Breast Neoplasms; Cancer Survivors; Estrogens; Female; Genital Neoplasms, Female; Hormone Replacement Therapy; Humans; Neoplasms; Neoplasms, Second Primary; Progesterone
PubMed: 30617760
DOI: 10.1007/s12253-018-00569-x -
American Journal of Obstetrics and... Aug 2020Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in... (Review)
Review
Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.
Topics: Abortion, Habitual; Abortion, Threatened; Administration, Intravaginal; Female; Humans; Pregnancy; Pregnancy Trimester, First; Progesterone; Progestins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32008730
DOI: 10.1016/j.ajog.2019.12.006 -
International Journal of Molecular... Jul 2022Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial... (Review)
Review
Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
Topics: Female; Hormones; Humans; Infant, Newborn; Pregnancy; Progesterone; Progestins
PubMed: 35887338
DOI: 10.3390/ijms23147989 -
International Journal of Molecular... Oct 2021The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name... (Review)
Review
The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means "promoting gestation", this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.
Topics: Abortion, Spontaneous; Female; Gonadotropin-Releasing Hormone; Humans; Immune System; Menstrual Cycle; Pregnancy; Premenstrual Syndrome; Progesterone; Tryptophan
PubMed: 34681696
DOI: 10.3390/ijms222011039 -
International Journal of Molecular... Nov 2022Progesterone is the ovarian steroid produced by the granulosa cells of follicles after the LH peak at mid-cycle. Its role is to sustain embryo endometrial implantation... (Review)
Review
Progesterone is the ovarian steroid produced by the granulosa cells of follicles after the LH peak at mid-cycle. Its role is to sustain embryo endometrial implantation and ongoing pregnancy. Other biological effects of progesterone may exert a protective function in supporting pregnancy up to birth. Luteal phase support (LPS) with progesterone is the standard of care for assisted reproductive technology. Progesterone vaginal administration is currently the most widely used treatment for LPS. Physicians and patients have been reluctant to change an administration route that has proven to be effective. However, some questions remain open, namely the need for LPS in fresh and frozen embryo transfer, the route of administration, the optimal duration of LPS, dosage, and the benefit of combination therapies. The aim of this review is to provide an overview of the uterine and extra-uterine effects of progesterone that may play a role in embryo implantation and pregnancy, and to discuss the advantages of the use of progesterone for LPS in the context of Good Medical Practice.
Topics: Pregnancy; Female; Humans; Progesterone; Beginning of Human Life; Lipopolysaccharides; Luteal Phase; Reproductive Techniques, Assisted
PubMed: 36430614
DOI: 10.3390/ijms232214138 -
Lancet (London, England) Mar 2021Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.
METHODS
We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.
FINDINGS
Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.
INTERPRETATION
Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.
FUNDING
Patient-Centered Outcomes Research Institute.
Topics: 17-alpha-Hydroxyprogesterone; Administration, Intravaginal; Decision Making, Shared; Female; Humans; Infant, Newborn; Injections, Intramuscular; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Premature Birth; Progesterone; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 33773630
DOI: 10.1016/S0140-6736(21)00217-8 -
Medicine and Science in Sports and... Dec 2019The aim of this review is to provide methodological recommendations for menstrual cycle research in exercise science and sports medicine based on a review of recent... (Review)
Review
INTRODUCTION
The aim of this review is to provide methodological recommendations for menstrual cycle research in exercise science and sports medicine based on a review of recent literature. Research in this area is growing but often reports conflicting results, and it is proposed that some of this may be explained by methodological issues.
METHODS
This review examined the menstrual cycle verification methods used in recent literature on exercise performance over the menstrual cycle identified through a literature search of PubMed and SportDiscus from 2008 until 2018.
RESULTS
Potential changes over the menstrual cycle are likely related to hormone fluctuations; however, only 44% of the selected studies measured the actual concentrations of the female steroid hormones estrogen and progesterone. It was shown that the likely inclusion of participants with anovulatory or luteal phase-deficient cycles in combination with small participant numbers has affected results in recent menstrual cycle research and, consequently, our understanding of this area.
CONCLUSION
To improve the quality of future menstrual cycle research, it is recommended that a combination of three methods is used to verify menstrual cycle phase: the calendar-based counting method combined with urinary luteinizing hormone surge testing and the measurement of serum estrogen and progesterone concentrations at the time of testing. A strict luteal phase verification limit of >16 nmol·L for progesterone should be set. It is also recommended that future research should focus on the inclusion of the late follicular estrogen peak. It is envisaged that these methodological recommendations will assist in clarifying some of the disagreement around the effects of the menstrual cycle on exercise performance and other aspects of exercise science and sports medicine.
Topics: Athletic Performance; Body Temperature; Estrogens; Exercise; Female; Humans; Luteinizing Hormone; Menstrual Cycle; Progesterone; Research Design; Saliva; Sports
PubMed: 31246715
DOI: 10.1249/MSS.0000000000002073