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Current Opinion in Obstetrics &... Dec 2022To review the current literature on the multiple types and uses of progestins in reproductive healthcare. (Review)
Review
PURPOSE OF REVIEW
To review the current literature on the multiple types and uses of progestins in reproductive healthcare.
RECENT FINDINGS
Progestins for contraceptive use are available in multiple forms, with the ongoing development of transdermal, intravaginal, and male contraception formulations. Noncontraceptive use of progestins often overlaps with contraceptive indications, which allows for simultaneous multipurpose progestin use, especially in reproductive-aged patients. More studies are needed to determine contraceptive doses of progestins used for noncontraceptive purposes. Side effect profiles of progestins are dependent on their formulation and cross-reactivity with other steroid receptors. Development of newer progestins includes manipulating pharmacologic properties to avoid undesired side effects.
SUMMARY
Progestins have multiple uses in reproductive healthcare, including contraception, menstrual suppression, endometrial protection, and hormonal replacement therapy. The development of progestins for these indications can expand therapy for people with contraindications to estrogen-based hormonal therapy.
Topics: Female; Humans; Male; Adult; Progestins; Contraceptives, Oral, Hormonal; Contraception; Estrogens; Administration, Cutaneous
PubMed: 36036464
DOI: 10.1097/GCO.0000000000000819 -
Best Practice & Research. Clinical... Nov 2020Natural progesterone (P4) has a unique pharmacodynamic activity and safety profile compared to the synthetic progestins. As a result, a class effect does not exist for... (Review)
Review
Natural progesterone (P4) has a unique pharmacodynamic activity and safety profile compared to the synthetic progestins. As a result, a class effect does not exist for both P4 and synthetic progestins, in terms of both their efficacy and safety. Progestogens act at the genomic level by binding to the nuclear receptors and modulating the expression of some target-genes. P4 and the synthetic progestins have a hugely variable affinity for binding not only to the P4 receptors but also to other members of the steroid receptor family including glucocorticoid receptor, androgen receptor and mineralocorticoid receptor. This leads to different and specific pharmacokinetic profiles, clinical pharmacodynamics, safety and efficacy. P4 produced in the luteal phase of the menstrual cycle has several physiological effects regulating menses and, in the pregnant uterus, controlling the development of endometrial receptivity preparing the endometrium for implantation. P4 and its associated metabolites are powerful biological agents through genomic action by the progesterone nuclear receptor with a finely tuned regulatory role throughout pregnancy, from conception until delivery. Extra-nuclear, non-classical mechanisms of action have also been identified, including steroid interactions with some membrane receptors [oxytocin receptors and γ-aminobutyric acid (GABA), and the induction of a direct relaxing effect on uterine contractility by blockage of calcium influx. The extent of activity of P4 on the central nervous system (CNS) is modulated by the route of administration: oral P4 is affected by the presence of bacteria and associated enzymes secreted in the gut, the intestinal wall and by the liver, whereas vaginal P4 is not. P4 and two important metabolites, namely, allopregnanolone (3a,5a-tetrahydroP4) and 3a,5a-tetrahydrodeoxycorticosterone, exert neuroprotective effects on neonates. They are also natural positive modulators of the neuronal GABA receptor, providing a clear pathway to explain the rapid dose-dependent psychopharmacological actions including anxiolytic, antidepressant, anaesthetic, anticonvulsant and analgesic effects. Fundamental structural differences exist between P4 and the synthetic progestins, resulting in different safety profiles when they are used during the menstrual cycle, in early and late pregnancy and in the alleviation of peri- or postmenopausal symptoms.
Topics: Endometrium; Female; Humans; Infant, Newborn; Menstrual Cycle; Pregnancy; Progesterone; Progestins; Receptors, Progesterone; Uterus
PubMed: 32739288
DOI: 10.1016/j.bpobgyn.2020.06.002 -
Presse Medicale (Paris, France : 1983) Nov 2019Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an...
Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an important public health issue. In this perspective, we conducted a review of the risk of hypertension associated with the use of hormonal contraceptives, either combined estrogen-progestin or only progestin. The use of combined hormonal contraceptives, regardless of its type and route of administration, is associated with a slight increase in blood pressure, both systolic and diastolic blood pressures. The frequency of onset of hypertension in women who use combined hormonal contraception is between 0.6% and 8.5%. Progestin-only contraception seems safe with respect to the risk of hypertension. It is therefore important to remember that the use of combined hormonal contraception is contra-indicated in hypertensive women, even well controlled. Finally, we propose a prescription assistance algorithm according to the recommendations of an expert panel. It should be remembered that taking blood pressure at each contraceptive consultation (initial and follow-up) is essential.
Topics: Adolescent; Adult; Blood Pressure; Blood Pressure Determination; Contraception; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Hypertension; Middle Aged; Progestins; Risk Factors; Young Adult
PubMed: 31757732
DOI: 10.1016/j.lpm.2019.07.033 -
Hormone Molecular Biology and Clinical... May 2020Progestational agents are often prescribed to increase the clinical pregnancy rate in assisted reproduction. Progestogens affect implantation, cytokine balance, natural... (Review)
Review
Progestational agents are often prescribed to increase the clinical pregnancy rate in assisted reproduction. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progesterone production from the corpus luteum is essential for reproduction, but assisted reproductive technologies (ART) can impair luteal function. ART cycles can be classified into three, fresh cycles in which there may or may not be luteal insufficiency, agonist or antagonist cycles in which there is luteal insufficiency, and luteal support is essential, and donor cycles, in which there is no corpus luteum, and a luteal phase has to be created. However, there is no adequate diagnostic test for luteal insufficiency. This article summarises the effect of various progestogens, progesterone itself whether administered vaginally, intra-muscularly, rectally or subcutaneously, and the effect of the progestogen, dydrogesterone. The time of commencement and cessation of therapy are also discussed. Progestogens are also often used to treat threatened and recurrent miscarriage. In these patients progestogen supplementation may need to be prolonged. In threatened miscarriage, until after all bleeding stops, and in recurrent miscarriage, at least as long as the luteo-placental shift.
Topics: Clinical Decision-Making; Clinical Trials as Topic; Disease Management; Endometrium; Female; Fertilization in Vitro; Humans; Luteal Phase; Pregnancy; Progesterone; Progestins; Reproductive Techniques, Assisted; Treatment Outcome
PubMed: 32432564
DOI: 10.1515/hmbci-2019-0067 -
BMJ Sexual & Reproductive Health Jan 2023
Topics: Humans; Progestins; Contraception
PubMed: 36198480
DOI: 10.1136/bmjsrh-2022-201666 -
American Family Physician Dec 2022Breastfeeding is universally recognized as the preferred method of infant nutrition, but is sometimes abbreviated because of fear of harm to the infant from maternal...
Breastfeeding is universally recognized as the preferred method of infant nutrition, but is sometimes abbreviated because of fear of harm to the infant from maternal medication. The amount of medication that enters breast milk varies based on the maternal serum concentration and the pharmacologic properties of the medication. When prescribing medications for a breastfeeding patient, those with the lowest risk to the infant should be selected, and dosing should be before the infant's longest sleep interval. Prescribers should use current, accurate resources. LactMed is a convenient, government-sponsored, authoritative resource that lists safety information for many medications and is available free online. When mental health conditions occur during lactation, priority should be given to effectively treating the mother, often with medications that were effective during pregnancy. Most antidepressants are compatible with breastfeeding. Stimulant medications may decrease milk supply. Insulin, metformin, and second-generation sulfonylureas are generally preferred to treat diabetes mellitus during breastfeeding, but newer agents require caution because they have not been studied in lactation. Inhaled and nasal treatments for asthma and allergic rhinitis are unlikely to affect breastfed infants. Acetaminophen and ibuprofen are preferred analgesics during lactation. Maternal opioid use can cause infant sedation. Herbal supplements are concerning for risk of impurities and lack of study of effects on breastfed infants. Nonhormonal and progestin-only contraceptives are preferred over combination oral contraceptives. Contrast for computed tomography or magnetic resonance imaging is not concerning during lactation, but use of radiopharmaceuticals, such as iodine 131, can accumulate in the lactating breast and increase risk to the infant.
Topics: Infant; Pregnancy; Female; Humans; Breast Feeding; Lactation; Milk, Human; Progestins; Contraceptives, Oral
PubMed: 36521462
DOI: No ID Found -
Revista Brasileira de Ginecologia E... Apr 2022
Topics: Contraceptives, Oral; Female; Humans; Progestins
PubMed: 35623623
DOI: 10.1055/s-0042-1748754 -
Neuroendocrinology 2023Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens, testosterone,... (Review)
Review
Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens, testosterone, progesterone and its reduced metabolites such as 5α-dihydro-progesterone and allopregnanolone. Steroids produced by neurons and glia target the nervous system and are called neurosteroids. Progesterone and analog molecules, known as progestogens, have been shown to exhibit neurotrophic, neuroprotective, antioxidant, anti-inflammatory, glial modulatory, promyelinating, and remyelinating effects in several experimental models of neurodegenerative and injury conditions. Pleiotropic mechanisms of progestogens may act synergistically to prevent neuron degeneration, astrocyte and microglial reactivity, reducing morbidity and mortality. The aim of this review is to summarize the significant findings related to the actions of progesterone and other progestogens in experimental models and epidemiological and clinical trials of some of the most prevalent and debilitating chronic neurodegenerative disorders, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We evaluated progestogen alterations under pathological conditions, how pathology modifies their levels, as well as the intracellular mechanisms and glial interactions underlying their neuroprotective effects. Furthermore, an analysis of the potential of natural progestogens and synthetic progestins as neuroprotective and regenerative agents, when administered as hormone replacement therapy in menopause, is also discussed.
Topics: Female; Humans; Progestins; Progesterone; Neuroprotection; Alzheimer Disease; Neurons
PubMed: 35760047
DOI: 10.1159/000525677 -
Annales D'endocrinologie May 2023
Topics: Humans; Progestins; Meningioma; Meningeal Neoplasms
PubMed: 36965850
DOI: 10.1016/j.ando.2023.03.017 -
Gynecological Endocrinology : the... May 2023No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and... (Review)
Review
No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.
Topics: Pregnancy; Adolescent; Humans; Female; Progestins; Hormonal Contraception; Contraception; Contraceptive Agents; Levonorgestrel; Contraceptive Agents, Female
PubMed: 37199597
DOI: 10.1080/09513590.2023.2214626