hydroxyprogesterone caproate / Generic mfg. - LARVOL DELTA

The current role of progesterone and cervical ultrasound in preventing the risk of preterm birth in the general population." (PubMed, Gynecol Obstet Fertil Senol) - "Seventeen alpha-hydroxyprogesterone caproate, a semi-synthetic progestin, has been disappointing, failing to reduce the risk of spontaneous preterm birth. Moreover, medical-economic analyses are converging to show that universal cervical length screening with vaginal progesterone treatment is cost-effective. Thus, the performance of vaginal ultrasound in selecting a population at risk of premature delivery in the general population due to a short cervix, combined with the effectiveness of treatment with vaginal progesterone to reduce this risk in the case of a short cervix, justifies the implementation of such screening."

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Clarifying Contradictions: Transportability in 17OHP-C Trials and Preterm Birth Outcomes Using Doubly Debiased Machine Learning. (PubMed, Am J Epidemiol) - "trial that identified a benefit of 17-alpha-hydroxyprogesterone caproate (17OHP-C) in reducing the risk of recurrent preterm birth (PTB) (risk difference (RD) -18.6%, 95% confidence interval (CI): -28.2%, -9.2%), a confirmatory trial (PROLONG) identified no benefit of 17OHP-C (RD: 1.2%, 95% CI: -3.0%, 5.3%)...Transporting from Meis to PROLONG did not recover the null point estimate observed in PROLONG, though the confidence interval was wide. Future studies should explore effect heterogeneity PTB."

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Treatment strategies for intra-amniotic infection and/or inflammation in preterm labor cases. (PubMed, Eur J Obstet Gynecol Reprod Biol X) - "We previously reported that 17-alpha-hydroxyprogesterone caproate (17OHP-C) effectively prolonged pregnancy by 4 weeks in PTL cases with mild intra-amniotic inflammation, but not in those with severe intra-amniotic inflammation...However, obstetrical interventions are limited once severe clinical symptoms appear. In addition to the use of drugs to control uterine contractions, antibiotics and/or 17OHP-C may be necessary in the treatment of PTL cases following the accurate assessment of intrauterine infection and/or inflammation is confirmed."

Journal • Alzheimer's Disease • Cerebral Palsy • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Mental Retardation • Obstetrics

Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function. (PubMed, Sci Adv) - "As a steroid hormone, progesterone is thought to modify uterine and placental morphology by altering gene expression, but another direct mode of action has long been suspected...Kir7.1 is also activated by selective steroids, including those used to prevent premature labor, such as 17-α-hydroxyprogesterone caproate and dydrogesterone, revealing their unexpected mode of action. Our results reveal that Kir7.1 is the molecular target of both endogenous and synthetic steroids that control uterine excitability and placental function. Kir7.1, therefore, is a promising therapeutic target to support healthy pregnancy during mid and late gestation."

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Vaginal progesterone for prevention of preterm birth in women with a history of preterm birth regardless of cervical length: an argument against use. (PubMed, Am J Obstet Gynecol MFM) - "However, more recent data suggesting limited efficacy led the US Food and Drug Administration to revoke approval of 17-alpha hydroxyprogesterone caproate (17-OHPC). As such, we argue against the universal use of vaginal progesterone supplementation for the prevention of recurrent preterm birth. VIDEO ABSTRACT."

Journal • Review

Vaginal administration of 17-alpha hydroxyprogesterone caproate appears to be safe in non-pregnant female rats and rabbits. (PubMed, Xenobiotica) - "There was no renal or hepatic toxicity as measured by liver function and kidney function tests.Intravaginal administration of 17-OHPC resulted in low systemic plasma concentrations but substantially higher uterus and adipose tissue concentrations of 17-OHPC. Composition of the formulation affected the tissue distribution of 17-OHPC.Future studies warrant further evaluation of the effect and safety of daily intravaginal administration of 17-OHPC gel in pregnant animals."

Journal • Preclinical • Hepatology

Developmental 17-OHPC exposure disrupts behavior regulated by the mesocorticolimbic dopaminergic system in rats. (PubMed, Pharmacol Biochem Behav) - "The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals with the intention of reducing preterm birth...These results suggest that exposure to 17-OHPC altered aspects of decision-making and latent inhibition in adult male rats, without affecting performance in a measure of spatial learning and memory. Further, the insensitivity of 17-OHPC-exposed males to an Eticlopride-induced increase in omissions suggests a dysfunction in the D2 receptor following exposure to this clinically used synthetic progestin."

Journal • Preclinical • DRD2

Simultaneous determination of 61 hormones in water by solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (PubMed, Se Pu) - "In this study, we established a rapid and high-throughput continuous online method based on solid phase extraction (SPE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 61 hormone components, including 48 glucocorticoids, 1 mineralocorticoid, 4 androgens, and 8 progesterones, in water...Using this method, we successfully detected 10 hormone components (cortisone, fluticasone propionate, ciclesonide, betamethasone dipropionate, clobetasone butyrate, diflucortolone valerate, halobetasol propionate, isoflupredone, difluprednate, and hydroxyprogesterone caproate) in various surface water and groundwater samples collected from the Taihu Basin region...Thus, it exhibits promising potential for tracing targeted hormone residues in water and will be of great value in monitoring and ensuring water safety. Finally, a regional analysis was conducted on the hormone levels in water, and suggestions were..."

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Implications of Developmental 17-OHPC Exposure on the Mesocorticolimbic Serotonergic and Dopaminergic Pathways and Adolescent Mood-Related Behavior in Rats. (PubMed, Dev Psychobiol) - "The synthetic progestin, 17-α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals at risk for recurrent preterm birth during a critical period of fetal mesocorticolimbic serotonergic and dopaminergic pathway development...Developmental 17-OHPC reduced the latency to immobility in males in the forced swim test but did not affect sucrose consumption in a sucrose preference test. These findings suggest that 17-OHPC exerts sex-specific effects on the development of mesocorticolimbic pathways and mood-related behavior in adolescence and highlight the need to investigate effects in adolescent children."

Journal • Preclinical

Progesterone supplementation reduces symptoms of preeclampsia in response to preeclamptic placental CD4+T cells in pregnant nude-athymic rats (ASRI 2024) - "Seventeen hydroxyprogesterone caproate (17-OHPC), a synthetic progesterone, lowered hypertension, CD4+T cells and proinflammatory cytokines while increasing pup weight in the reduced uterine perfusion pressure (PE mimic) rat model. Collectively, these data indicate that placental CD4+ T cells play an important role in the pathophysiology of preeclampsia and 17-OHPC reduces the signs of PE in pregnant nude-athymic rats by reducing maternal blood pressure and AT1-AA."

Preclinical • Cardiovascular • Gynecology • Hypertension • Inflammation • Renal Disease • CD4

Suppression of progesterone by influenza A virus causes sex differential adverse fetal outcomes in mice (ASRI 2024) - "A subset of dams were infected with H1N1 and treated with 17-alpha-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin, or vehicle. In addition to its role in promoting fetal tolerance, P4 is a known regulator of spiral artery remodeling during pregnancy, and thus dysregulation of placental angiogenesis may play a mechanistic role in driving sex-differential adverse outcomes, with a more dramatic impact on placental development in males. These data reflect patterns seen in other pregnancy pathologies, providing mechanistic insight that can be applied to further therapeutic efforts to reduce adverse fetal outcomes caused by influenza."

Adverse events • Preclinical • Developmental Disorders • Gynecology • Infectious Disease • Inflammation • Influenza • Respiratory Diseases • CD80 • IL1B • IL6 • KDM5C • TNFA

The Dosing Regimen for 17-hydroxyprogesterone caproate was Suboptimal Lessons for Future Pharmacotherapy for Pregnant Women. (PubMed, Am J Obstet Gynecol) - "The dosing regimen for 17-hydoxyprogesterone caproate was inadequate. There is a significant inverse relationship between drug concentration and spontaneous preterm birth. Risk is lowest when concentration exceeds 9 ng/ml but 25% of women receiving the 250 mg weekly dose will never reach and maintain this concentration. The drug's long half-life necessitates a loading dose to achieve therapeutic concentrations rapidly. The omission of basic pharmacologic studies to determine the proper dosing may have compromised the effectiveness of 17-hydroxyprogesterone caproate. Future pharmacotherapy trials in pregnancy must first complete fundamental pharmacology studies."

Journal • Obstetrics

Developmental exposure to 17-α-hydroxyprogesterone caproate disrupts decision-making in adult female rats: A potential role for a dopaminergic mechanism. (PubMed, Horm Behav) - "The dopamine transporter inhibitor, methylphenidate (MPH), was administered prior to delay discounting testing. These results suggest that developmental 17-OHPC exposure increased omissions without affecting impulsivity or slowing decision-making. Furthermore, omissions may be regulated, at least in part, by dopaminergic mechanisms."

Journal • Preclinical

Progesterone therapy for prevention of recurrent spontaneous preterm birth in a minority patient population: a retrospective study. (PubMed, BMC Pregnancy Childbirth) - "Progesterone therapy of any type did not reduce the risk of recurrent sPTB < 34 or < 37 weeks' gestation compared to no progesterone therapy."

Journal • Retrospective data

Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin 1 Suppression in Female Mice with Increased Anxiety-Like Behaviors. (PubMed, Neuroendocrinology) - "17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice."

Journal • Preclinical • Gastrointestinal Disorder • Mood Disorders • Psychiatry • CLDN1 • ER • VDR

Concurrent Progestogen and Cerclage to Reduce Preterm Birth: a multicenter international retrospective cohort. (PubMed, Am J Obstet Gynecol MFM) - "Use of progestogen with cerclage was associated with reduced rates of sPTB and early sPTB compared to cerclage alone. Although not powered for subgroups, the strength of evidence for benefit appeared greatest for those with ultrasound or exam-indicated cerclage, and with vaginal progesterone."

Journal • Retrospective data • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Hematological Disorders • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • Retinopathy of Prematurity • Septic Shock

Management of a pregnant woman with a large cervical polyp and moderate genital bleeding in the first trimester. (PubMed, BMJ Case Rep) - "We managed a pregnant woman in her 30s with a large cervical polyp without polypectomy, and we administered probiotics including Clostridium butyricum and 17-alpha-hydroxyprogesterone caproate. As a result, she delivered a healthy baby at 38 weeks."

Journal • Gynecology • Obstetrics

Nationwide status of progestogen treatment to prevent spontaneous preterm birth: A questionnaire survey for childbirth healthcare facilities in Japan. (PubMed, J Obstet Gynaecol Res) - "Due to the current regulations of the Japanese health insurance system, 17α-hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan."

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Challenges in Using Progestin to Prevent Singleton Preterm Births: Current Knowledge and Clinical Advice. (PubMed, Int J Womens Health) - "Progesterone is a natural progestogen while progestins such as 17-alpha-hydroxyprogesterone caproate (17OHP-C) are synthetic steroid hormones. With this decision, there is no current FDA-approved treatment for prevention of spontaneous preterm birth. In this review, we provide a historical context behind the rise and fall of 17OHP-C clinical application, highlight the challenges behind the data supporting progestogen use, and offer suggestions on how to make an impact on preterm birth moving forward."

Journal • Review • Mood Disorders • Obstetrics • Psychiatry

Discontinuation Of Long-Established Hydroxyprogesterone Caproate; Call For Awareness And Drug-Substitutes: A Letter To The Editor. (PubMed, J Pak Med Assoc) - No abstract available

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Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth (clinicaltrials.gov) - P1/2 | N=159 | Terminated | Sponsor: Steve N. Caritis, MD | Phase classification: P2/3 ➔ P1/2 | Completed ➔ Terminated; grant funding cycle ended

Phase classification • Trial termination

Randomized Controlled Trials: Not Always The "Gold Standard" For Evidence in Obstetrics & Gynecology. (PubMed, Am J Obstet Gynecol) - "Some reversals in widely adopted clinical practice have recently been implemented following subsequent studies that contradicted the outcomes of major RCTs; the most notable of these being the withdrawal from the market of 17-hydroxyprogesterone caproate for preterm birth prevention...This Clinical Opinion underscores the limitations of an exclusive reliance on RCTs while disregarding other evidence in determining how best to care for patients. Solutions are proposed that advocate that clinicians adopt a more balanced perspective that considers the entirety of the available medical evidence as well as the individual patient characteristics, needs, and wishes."

Gold standard • Journal • Gynecology • Obstetrics

The end is where we start from: withdrawal of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth. (PubMed, Am J Obstet Gynecol) - No abstract available

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Placental Histology for Targeted Risk Assessment of Recurrent Spontaneous Preterm Birth and Response to 17-alpha hydroxy-progesterone caproate Supplementation. (PubMed, Am J Obstet Gynecol) - "While AI was prevalent among spontaneous preterm births, over half of spontaneous preterm births were not associated with AI. Low grade AI was associated with significantly decreased response to 17-OHPC supplementation. Low grade MVM was associated with 4 fold increase likelihood of 17-OHPC response among those with index deliveries < 36 weeks. Further work is needed to determine whether placental pathological examination can be utilized to target treatment in subsequent pregnancies to prevent rPTB."

Journal • Inflammation • Obstetrics • PGR

Prediction and Prevention of Preterm Birth: Secondary Analysis of a Randomized Intervention Trial. (PubMed, J Clin Med) - "In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We conclude that screening with the PreTRM test followed by interventions for screen-positive pregnancies may prolong pregnancy and reduce NICU LOS, but these observations need to be confirmed by additional research."

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