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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 -
Neuroscience Letters Jan 2021Progesterone acts on neurons directly by activating its receptor and through metabolic conversion to neurosteroids. There is emerging evidence that progesterone exerts... (Review)
Review
Progesterone acts on neurons directly by activating its receptor and through metabolic conversion to neurosteroids. There is emerging evidence that progesterone exerts excitatory effects by activating its cognate receptors (progesterone receptors, PRs) through enhanced expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Progesterone metabolite 5α,3α-tetrahydro-progesterone (allopregnanolone, THP) mediates its anxiolytic and sedative actions through the potentiation of synaptic and extrasynaptic γ-aminobutyric acid type-A receptors (GABARs). Here, we review progesterone's neuromodulatory actions exerted through PRs and THP and their opposing role in regulating seizures, catamenial epilepsy, and seizure exacerbation associated with progesterone withdrawal.
Topics: Animals; Anticonvulsants; Epilepsy; GABA-A Receptor Antagonists; Humans; Neurons; Progesterone; Receptors, GABA-A; Receptors, Progesterone
PubMed: 33421486
DOI: 10.1016/j.neulet.2020.135619 -
Best Practice & Research. Clinical... Nov 2020Mood and anxiety disorders are vastly overrepresented in women, and one important contributor to these differences is the fluctuation in sex steroids in women during the... (Review)
Review
Mood and anxiety disorders are vastly overrepresented in women, and one important contributor to these differences is the fluctuation in sex steroids in women during the reproductive years. Considerable evidence supports a role for abnormal sensitivity to these hormonal fluctuations for some women, who develop mood symptoms associated with reproductive transitions. This chapter presents evidence of the role of endogenous progesterone and its metabolites in such mood symptoms, and then goes on to cover the evidence concerning exogenous progesterone's effects on mood. Overall, the literature does not support an association between exogenous progesterone and negative mood in the general population, but does indicate that subset of women may be vulnerable to such effects. Research is lacking on women with psychiatric illness.
Topics: Affect; Female; Humans; Mood Disorders; Progesterone; Reproduction
PubMed: 32723604
DOI: 10.1016/j.bpobgyn.2020.06.001 -
Hormones and Behavior Feb 2013Numerous studies aimed at identifying the role of estrogen on the brain have used the ovariectomized rodent as the experimental model. And while estrogen intervention in... (Review)
Review
Numerous studies aimed at identifying the role of estrogen on the brain have used the ovariectomized rodent as the experimental model. And while estrogen intervention in these animals has, at least partially, restored cholinergic, neurotrophin and cognitive deficits seen in the ovariectomized animal, it is worth considering that the removal of the ovaries results in the loss of not only circulating estrogen but of circulating progesterone as well. As such, the various deficits associated with ovariectomy may be attributed to the loss of progesterone as well. Similarly, one must also consider the fact that the human menopause results in the precipitous decline of not just circulating estrogens, but in circulating progesterone as well and as such, the increased risk for diseases such as Alzheimer's disease during the postmenopausal period could also be contributed by this loss of progesterone. In fact, progesterone has been shown to exert neuroprotective effects, both in cell models, animal models and in humans. Here, we review the evidence that supports the neuroprotective effects of progesterone and discuss the various mechanisms that are thought to mediate these protective effects. We also discuss the receptor pharmacology of progesterone's neuroprotective effects and present a conceptual model of progesterone action that supports the complementary effects of membrane-associated and classical intracellular progesterone receptors. In addition, we discuss fundamental differences in the neurobiology of progesterone and the clinically used, synthetic progestin, medroxyprogesterone acetate that may offer an explanation for the negative findings of the combined estrogen/progestin arm of the Women's Health Initiative-Memory Study (WHIMS) and suggest that the type of progestin used may dictate the outcome of either pre-clinical or clinical studies that addresses brain function.
Topics: Animals; Brain; Cognition; Cytoprotection; Humans; Neuroprotective Agents; Progesterone; Progesterone Congeners; Receptors, Progesterone
PubMed: 22732134
DOI: 10.1016/j.yhbeh.2012.06.003 -
Climacteric : the Journal of the... Aug 2018Estradiol (E2) is women's dominant 'bone hormone' since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent... (Meta-Analysis)
Meta-Analysis Review
Estradiol (E2) is women's dominant 'bone hormone' since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent the rapid (3-week) bone resorption that causes most adult BMD loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone (P4) is E2's physiological partner, collaborating with E2 in every cell/tissue; its bone 'job' is to increase P4-receptor-mediated, slow (3-4 months) osteoblastic new bone formation. When menstrual cycles are normal length and normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically normal cycles commonly have ovulatory disturbances (anovulation, short luteal phases) and low P4 levels; these are more frequent in teen and perimenopausal women and increased by everyday stressors: energy insufficiency, emotional/social/economic threats and illness. Meta-analysis shows that almost 1%/year spinal BMD loss occurs in those with greater than median (∼31%) of ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures requires the reversal of stressors, detection and treatment of teen-to-perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized progesterone. Low 'Peak Perimenopausal BMD' is likely the primary risk for fragility fractures in later life. Progesterone plus estradiol or other antiresorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. Randomized controlled trials are still needed to confirm progesterone's important role in women's bone formation.
Topics: Aging; Bone Density; Estradiol; Female; Humans; Menopause; Menstrual Cycle; Osteoporosis; Progesterone; Risk
PubMed: 29962257
DOI: 10.1080/13697137.2018.1467400 -
Endocrine Apr 2006Estrogen and progesterone are two steroid hormones whose biology has been greatly studied within the confines of reproductive function. As a consequence, the effects of... (Review)
Review
Estrogen and progesterone are two steroid hormones whose biology has been greatly studied within the confines of reproductive function. As a consequence, the effects of these hormones on the brain have focused primarily on the hypothalamus. Growing evidence, however, forces us to recognize that various extrahypothalamic brain regions, including the cerebral cortex and hippocampus, are equally important targets of these hormones. As such, hormones are involved in numerous aspects of brain function, and elicit effects ranging from the regulation of mood and cognition to the regulation of neuronal survival. While estrogen exerts neuroprotective effects in various experimental models, the potential for progesterone as a protective agent has, until recently, been greatly understudied. Here, we review the data from various laboratories including our own that support the protective role of progesterone and describe the multiplicity of mechanisms by which progesterone elicits these protective effects. Finally, we contrast the neurobiology of progesterone with that of the clinically used progestin, medroxyprogesterone acetate (MPA), and suggest that the "natural" progesterone may be the better choice when considering which progestin to use for future therapeutic/ palliative purposes in CNS-related disorders.
Topics: Animals; Brain; Humans; Medroxyprogesterone Acetate; Neuroprotective Agents; Progesterone
PubMed: 16785602
DOI: 10.1385/ENDO:29:2:271 -
Climacteric : the Journal of the... Aug 2018
Topics: History, 20th Century; History, 21st Century; Humans; Progesterone
PubMed: 29991304
DOI: 10.1080/13697137.2018.1462910 -
Seizure Dec 2018The anti-seizure effects of progesterone family compounds have long been known. Over the years, however, most studies have focused on progesterone and on its secondary... (Review)
Review
The anti-seizure effects of progesterone family compounds have long been known. Over the years, however, most studies have focused on progesterone and on its secondary metabolite allopregnanolone (ALLO), with less attention being paid to its primary metabolite 5a-dihydroprogesterone (DHP). Here we review animal and clinical studies related to the anti-seizure effects of progesterone and its 5a neuroactive metabolites, including DHP and ALLO. Progesterone and its reduced metabolites all have demonstrated seizure-suppression effects in animal models - except in models of absence seizures - with the common side effects of sedation and ataxia. Progesterone and ALLO have also shown anti-seizure effects in clinical trials. A large Phase III trial has revealed that female patients with premenstrual exacerbations of seizures benefit most from progesterone therapy. A liquid suspension of ALLO has also been tested in patients with supra-refractory status epilepticus with some success in a small phase II trial. ALLO's C3 methyl analog ganaxolone is under development as an anti-seizure drug. Progesterone's anti-seizure effects are mostly independent of its genomic receptors and are, in large part, due to its active metabolites. ALLO is a potent allosteric modulator of GABA receptors. Other membrane receptors are thought to be involved in the DHP's anti-seizure actions, but their exact nature is not yet known. Potential drawbacks to the development of progesterone family compounds as anti-seizure drug are their endocrine effects. These compounds might form a basis for the future development of novel anti-seizure drugs, however, with hormonal side effects being mitigated through rational drug design.
Topics: 20-alpha-Dihydroprogesterone; Animals; Anticonvulsants; Humans; Pregnanolone; Progesterone; Seizures
PubMed: 30391663
DOI: 10.1016/j.seizure.2018.10.012 -
Neuroscience Jun 2013While the effects of progesterone in the CNS, like those of estrogen, have generally been considered within the context of reproductive function, growing evidence... (Review)
Review
While the effects of progesterone in the CNS, like those of estrogen, have generally been considered within the context of reproductive function, growing evidence supports its importance in regulating non-reproductive functions including cognition and affect. In addition, progesterone has well-described protective effects against numerous insults in a variety of cell models, animal models and in humans. While ongoing research in several laboratories continues to shed light on the mechanism(s) by which progesterone and its related progestins exert their effects in the CNS, our understanding is still incomplete. Among the key mediators of progesterone's beneficial effects is the family of growth factors called neurotrophins. Here, we review the mechanisms by which progesterone regulates one important member of the neurotrophin family, brain-derived neurotrophic factor (BDNF), and provides support for its pivotal role in the protective program elicited by progesterone in the brain.
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Humans; Neuroprotective Agents; Progesterone
PubMed: 23036620
DOI: 10.1016/j.neuroscience.2012.09.056 -
Biochemical Pharmacology Apr 2022There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals,... (Review)
Review
There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals, such as bisphenol A, and pesticides, such as DDT. These endocrine-disrupting chemicals influence steroid-mediated physiology in humans and other vertebrates by competing with steroids for receptor binding sites, disrupting diverse responses involved in reproduction, development and differentiation. Here I discuss that due to evolution of the progesterone receptor (PR) and mineralocorticoid receptor (MR) after ray-finned fish and terrestrial vertebrates diverged from a common ancestor, each receptor evolved to respond to different steroids in ray-finned fish and terrestrial vertebrates. In elephant shark, a cartilaginous fish that diverged before the separation between ray-finned fish and terrestrial vertebrates, both progesterone and 17,20β-dihydroxy-progesterone activate the PR. During the evolution of ray-finned fish and terrestrial vertebrates, the PR in terrestrial vertebrates continued responding to progesterone and evolved to weakly respond to 17,20β-dihydroxy-progesterone. In contrast, the physiological progestin for the PR in zebrafish and other ray-finned fish is 17,20β-dihydroxy-progesterone, and ray-finned fish PR responds weakly to progesterone. The MR in fish and terrestrial vertebrates also diverged to have different responses to progesterone. Progesterone is a potent agonist for elephant shark MR, zebrafish MR and other fish MRs, in contrast to progesterone's opposite activity as an antagonist for aldosterone, the physiological mineralocorticoid for human MR. These different physiological ligands for fish and terrestrial vertebrate PR and MR need to be considered in applying data for their disruption by chemicals in fish and terrestrial vertebrates to each other.
Topics: Aldosterone; Animals; Progesterone; Receptors, Mineralocorticoid; Sharks; Zebrafish
PubMed: 35149051
DOI: 10.1016/j.bcp.2022.114951