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Alternative Therapies in Health and... Nov 2017Context • The medical literature on the use of progesterone in postmenopausal women is often confusing and contradictory. Some physicians implicate natural... (Review)
Review
Context • The medical literature on the use of progesterone in postmenopausal women is often confusing and contradictory. Some physicians implicate natural progesterone in an increase in the risk of breast cancer. The chemical structure of natural progesterone (P4) is quite different from chemically altered, synthetic chemicals called progestins, which results in different actions at the cell level. Objective • The research team intended to review the literature to examine the benefits and safety of natural progesterone and determine whether it can cause an increase or decrease in breast cancer risk. Design • A review of the medical literature to examine the benefits and safety of natural progesterone as compared with synthetic progestins. Intervention • Studies examined compared controls not receiving hormone therapy with women receiving estrogen alone and in combination with natural progesterone and with various synthetic progestins, such as medroxyprogesterone acetate-the most commonly used synthetic progestin. Outcome Measures • Outcome measures included factors such as progression and survival of breast and other cancers and other epidemiological and laboratory data. Results • A meta-analysis of 3 studies involving 86 881 postmenopausal women reported that the use of natural progesterone was associated with a significantly lower risk of breast cancer compared with synthetic progestins. Anovulation and low levels of serum progesterone have been associated with a significantly higher risk of breast cancer in premenopausal women. Use of progesterone has been linked to lower rates of uterine and colon cancers and may also be useful in treating other cancers such as ovarian, melanoma, mesothelioma, and prostate. Progesterone may also be helpful in preventing cardiovascular disease and preventing and treating neurodegenerative conditions such a stroke and traumatic brain injury. Conclusions • Physicians should have no hesitation prescribing natural progesterone. The evidence is clear that progesterone does not cause breast cancer. Indeed, progesterone is protective and preventative of breast cancer.
Topics: Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Humans; Progesterone; Progesterone Congeners; Progestins
PubMed: 29055286
DOI: No ID Found -
Clinics in Perinatology Dec 2014Spontaneous preterm labor is a complex process characterized by the interplay of multiple different pathways. Prevention of preterm labor and delivery is also... (Review)
Review
Spontaneous preterm labor is a complex process characterized by the interplay of multiple different pathways. Prevention of preterm labor and delivery is also complicated. The most effective interventions for prevention of preterm birth (PTB) are progestin prophylaxis and lifestyle modifications, with cerclage placement also playing a role in selected populations. Interventions such as activity modification, home tocometry, and routine antibiotic use have fallen out of favor because of lack of effectiveness and possibility of harm. The solution to the problem of PTB remains elusive, and researchers and clinicians must collaborate to find a cure for preterm labor.
Topics: Bed Rest; Cerclage, Cervical; Female; Humans; Pessaries; Pregnancy; Premature Birth; Progestins; Smoking Cessation; Tocolytic Agents
PubMed: 25459773
DOI: 10.1016/j.clp.2014.08.003 -
Drug Metabolism and Disposition: the... Jun 2023Combined oral contraceptives (COCs) are widely used in women of reproductive age in the United States. Metabolism plays an important role in the elimination of estrogens... (Review)
Review
Combined oral contraceptives (COCs) are widely used in women of reproductive age in the United States. Metabolism plays an important role in the elimination of estrogens and progestins contained in COCs. It is unavoidable that a woman using COCs may need to take another drug to treat a disease. If the concurrently used drug induces enzymes responsible for the metabolism of progestins and/or estrogens, unintended pregnancy or irregular bleeding may occur. If the concurrent drug inhibits the metabolism of these exogenous hormones, there may be an increased safety risk such as thrombosis. Therefore, for an investigational drug intended to be used in women with reproductive potential, evaluating its effects on the pharmacokinetics of COCs is important to determine if additional labeling is necessary for managing drug-drug interactions (DDIs) between the concomitant product and the COCs. It is challenging to determine when this clinical drug interaction study is needed, whether an observed exposure change of progestin/estrogen is clinically meaningful, and if the results of a clinical drug interaction study with one COC can predict exposure changes of unstudied COCs to inform labeling. In this review, we summarize the current understanding of metabolic pathways of estrogens and progestins contained in commonly used COCs and known interactions of these COCs as victim drugs and we discuss possible mechanisms of interactions for unexpected results. We also discuss recent advances, knowledge gaps, and future perspectives on this important topic. The review will enhance the understanding of DDIs with COCs and improve the safe and effective use of COCs. SIGNIFICANCE STATEMENT: This minireview provides an overview of the metabolic pathways of ethinyl estradiol and progestins contained in commonly used combined oral contraceptives (COCs) and significant drug interactions of these COCs as victims. It also discusses recent advances, knowledge gaps, future perspectives, and potential mechanisms for unexpected results of clinical drug interaction studies of COCs. This minireview will help the reader understand considerations when evaluating the drug interaction potential with COCs for drugs that are expected to be used concurrently.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Ethinyl Estradiol; Estrogens; Drug Interactions
PubMed: 36963837
DOI: 10.1124/dmd.122.000854 -
Best Practice & Research. Clinical... Oct 2018Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. The only medicinal therapy currently recommended to prevent PTB is prophylactic... (Review)
Review
Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. The only medicinal therapy currently recommended to prevent PTB is prophylactic progestin therapy in the form of micronized progesterone (P4) administered daily via vaginal suppository from the 24th to the 34th week of gestation or 17α-hydroxyprogesterone caproate in oil administered weekly from the 16th to the 36th week of gestation via an intramuscular injection. These therapies decrease the risk of PTB in women with an elevated risk of PTB indicated by a history of PTB or by a short cervix measured by sonography at mid-gestation. The mechanism by which progestin therapy prevents PTB in some women is not clear but may involve non-progestin mechanism and/or supplementation of localized progestin deficiency. Advances in understanding the molecular biology and physiology of P4 signaling via the P4 receptor isoforms in uterine cells reveal novel therapeutic targets; this may improve the effectiveness of progestin therapy to prevent PTB in the majority of pregnancies by targeting key steps in the pathway leading to inflammation-induced parturition.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Administration, Intravaginal; Cervical Length Measurement; Clinical Trials as Topic; Female; Humans; Injections, Intramuscular; Pituitary Gland; Pregnancy; Premature Birth; Progestins; Uterus
PubMed: 29724668
DOI: 10.1016/j.bpobgyn.2018.03.008 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
American Family Physician Feb 2024Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of...
Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of contraception and unintended pregnancies. Clinicians should counsel individuals about the potential for abnormal bleeding at initiation of the contraceptive method. After considering and excluding other potential causes of abnormal uterine bleeding, clinicians can offer treatment options specific to each hormonal contraceptive method. This article includes algorithms to help clinicians treat abnormal uterine bleeding in people using levonorgestrel intrauterine devices, depo-medroxyprogesterone acetate, progestin implant, progestin-only pills, and combined hormonal contraception. For patients with levonorgestrel intrauterine devices, physicians should first ensure that the device is correctly placed within the uterus, then consider nonsteroidal anti-inflammatory drugs as a first-line treatment for abnormal uterine bleeding; estradiol can be used if nonsteroidal anti-inflammatory drugs are ineffective. For depo-medroxyprogesterone acetate or progestin implant users, combined oral contraceptives or nonsteroidal anti-inflammatory drugs may be considered. For patients using norethindrone progestin-only pills, changing to drospirenone progesterone-only pills may help reduce the bleeding. In people using combined hormonal contraception, it may be helpful to increase estrogen content from 20 mcg to 35 mcg per day, decrease the hormone-free interval (from seven to four or five days) in people using cyclic contraception, or start a trial of low-dose doxycycline. For continuous combined contraception users, adding a hormone-free interval of four or five days can help regulate bleeding patterns.
Topics: Pregnancy; Female; Humans; Levonorgestrel; Progestins; Medroxyprogesterone Acetate; Hormonal Contraception; Contraception; Uterine Hemorrhage; Anti-Inflammatory Agents; Contraceptives, Oral, Hormonal
PubMed: 38393800
DOI: No ID Found -
Expert Opinion on Emerging Drugs Dec 2023Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line... (Review)
Review
INTRODUCTION
Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy.
AREAS COVERED
The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis.
EXPERT OPINION
Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.
Topics: Female; Humans; Endometriosis; Hormone Antagonists; Progestins; Estrogens; Gonadotropin-Releasing Hormone; Clinical Trials, Phase II as Topic
PubMed: 38099328
DOI: 10.1080/14728214.2023.2296080 -
BMJ Sexual & Reproductive Health Apr 2021
Topics: Humans; Intrauterine Devices; Progestins; Reproductive Health Services
PubMed: 33850008
DOI: 10.1136/bmjsrh-2021-201095 -
Journal of Neuroendocrinology Jul 2016When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids.... (Review)
Review
When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase, cytochrome P450arom, steroid 5α-reductase and 3α-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.
Topics: Animals; Brain; Estrogens; Humans; Neuroprotective Agents; Progestins; Receptors, Neurotransmitter
PubMed: 27306650
DOI: 10.1111/jne.12402 -
Cancer Medicine Mar 2023Progestins are used as fertility-sparing regimens for young patients with stage 1A endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH)....
BACKGROUND
Progestins are used as fertility-sparing regimens for young patients with stage 1A endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH). CD163 macrophages promote estrogen-dependent EEC development, but whether they induce progestin insensitivity remains unclear. This study aimed to investigate the possible effects of CD163 macrophages on progestin response in AEH/EEC patients.
METHODS
The number of infiltrating CD163 macrophages in progestin-insensitive and -sensitive endometrial lesions was compared. The effects of CD163 macrophages on progestin responses and progesterone receptor (PR) expression in EC cells were evaluated in vitro. ATAC-seq and RNA-seq were combined to identify molecular/biological changes induced by CD163 macrophages in progestin-insensitive EC cells.
RESULTS
Increased CD163 macrophage infiltration was significantly associated with progestin insensitivity and longer treatment durations in AEH/EEC patients. Additionally, the number of CD163 macrophages was negatively correlated with PR expression in AEH/EEC tissues. Furthermore, the CD163 macrophage-mediated microenvironment and secreted cytokines downregulated PR expression and impaired the response of EC cells to medroxyprogesterone acetate (MPA). RNA-seq analysis demonstrated that CD163 macrophages antagonized PR signaling by blocking or even reversing MPA-regulated differential gene expression. Based on RNA-seq and ATAC-seq analyses, extracellular matrix (ECM) signaling and ECM-related transcription factors, FOXF2, POU1F1, and RUNX1were identified to potentially be involved in CD163 macrophage-induced progestin insensitivity in endometrial cancer patients.
CONCLUSIONS
We identified CD163 macrophages as an important mediator of progestin desensitization and an unfavorable factor for the efficacy of fertility-preserving treatment in AEH/EEC patients.
Topics: Female; Humans; Progestins; Chromatin Immunoprecipitation Sequencing; RNA-Seq; Endometrial Neoplasms; Medroxyprogesterone Acetate; Progesterone; Endometrial Hyperplasia; Carcinoma, Endometrioid; Macrophages; Tumor Microenvironment; Forkhead Transcription Factors
PubMed: 36373483
DOI: 10.1002/cam4.5396