1,721,045 research outputs found
Androgen replacement therapy and cardiovascular function.
No full textAndrogens play a primary role in female physiopathology. The age-related decline in the production of ovarian and adrenal androgens may significantly affect women's health. Scanty studies have been designed to establish whether androgen deficiency might directly affect cardiovascular biology and whether it might be a risk factor for cardiovascular disease in women during reproductive aging. The present short review examines the effect of androgen on the cardiovascular system, with particular regard to dehydroepiandrosterone and testosterone replacement in postmenopausal wome
DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence
No full textThe marked age-related decline in serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) has suggested that a deficiency of these steroids may be causally related to the development of a series of diseases that are generally associated with aging. Postulated consequences of low DHEA levels include insulin resistance, obesity, cardiovascular disease, cancer, reduction of the immune defence system as well as psychosocial problems such as depression and a general deterioration in the sensation of well-being and cognitive function. Clinically, the spectrum of women that would benefit from DHEA therapy is not clearly defined and nor is the dosage of hormone treatment. Whether DHEA therapy could be prescribed as a general anti-aging therapy or could be an alternative treatment for women suffering from androgen deficiency syndrome remains uncertain across studies. The lack of definitive evidence for biological mechanisms and the presence of only a few studies that address these emerging issues of DHEA therapy in postmenopausal women might encourage a new critical analysis of the available literature, evidencing current limits and incongruities
Androgens and the brain
No full textSteroids arriving from the gonads via the circulation modulate brain function, affecting gender differentiation and sexually differentiated behavioral responses, but also the ability of the brain to process, store and retrieve sensory information. Androgens play a pivotal neuroactive role during the "organizational/developmental" phase, mainly in the fetal-neonatal period, when participated to the formation of neuronal circuits, as well as during the aging process when it has been demonstrated to directly affect hippocampal spine synapse density, suggesting a physiopathological role for androgen in the modulation cognitive function and development of neurodegenerative disease. The present short review will focus on the neuroactive effect of androgen with particular regard to the Delta4 and Delta5 androgen replacement therapy
Estrogen, cognition and female ageing
No full textStarting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of β-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged ≥65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed. © 2007 Oxford University Press
Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women.
No full textTibolone is a synthetic molecule used extensively for the management of menopausal symptoms, with the proposed additional advantage of enhanced mood and libido. Tibolone, after oral administration, is rapidly converted into 3 major metabolites: 3alpha-hydroxytibolone and 3beta-hydroxytibolone, which have estrogenic effects, and the Delta(4)-isomer, which has progestogenic and androgenic effects. The tissue-selective effects of tibolone are the result of metabolism, of enzyme regulation, and of receptor activation which vary in different tissues. Tibolone seems to be effective on estrogen-withdrawal symptoms such as hot flushes, sweating, insomnia, headache, and vaginal dryness, with results generally comparable to the effects exerted by estrogen-based treatments, and the additional property of a progestogenic activity on the endometrium. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves dyspareunia and libido. These effects may depend on both estrogenic and androgenic actions exerted at the genital level and in the central nervous system, and on a reduction of sex-hormone-binding globulin and an increase of free testosterone, without affecting Delta-5 androgens levels. Based on the evidence available, tibolone is a valuable treatment option to relieve menopausal complaints, especially in women suffering persistent fatigue, blunted motivation, and loss of sexual desire despite an adequate estrogen replacement
Estrogen, cognition and female ageing
No full textStarting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of beta-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged >or=65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed
Menopause and mental well-being: timing of symptoms and timing of hormone treatment.
No full textIn the aftermath of the Women's Health Initiative studies, both the clinical and basic science communities had to sort out divergent results among experimental findings, observational data and randomized controlled trials in order to establish a shared analysis. The scientific community formally debates the role of different HRT formulations, hormone doses, time of treatment initiation since the menopause and the age of treated women. Basic scientists demonstrated that the multiple neuroprotective effects of estrogen on brain cells may induce a differential biological response according to the time of treatment. Progesterone (but not all synthetic progestins) also has pivotal neuroactive functions in animal models of reproductive aging. Additionally, epidemiological surveys provide information regarding the detrimental role of hypogonadism on mental well-being. The present article briefly summarizes current evidence supporting the neuroactive role of estrogen, with reference to the clinical finding sustaining the intriguing hypothesis of the early female brain senescence as a highly responsive period to estrogen treatment
Comparative effects of dydrogesterone and medroxyprogesterone acetate in critical areas: The brain and the vessels
No full textSeveral epidemiological and observational studies have investigated the role of hormone replacement therapy (HRT) in postmenopausal women. Within a few years, clinicians shifted from considering HRT as the panacea for everything to considering it a venomous poison with which women, in search of the fountain of eternal youth, could instead harm themselves. This debate is not yet settled and the unexplained discrepancy between basic science and some of the clinical trials has fueled the discussion. One of the hottest areas of discussion remains the role of progestins. For many years, progestins were considered only as necessary additions to estrogen to protect the endometrium. However, we now know that every progestin has its own specific activities on different tissues, which can vary significantly between progestins of different classes and even within the same class. Indeed, different progestins may support or oppose the effects of estrogen depending on the tissue, thereby supporting the concept that the clinical selection of progestins for HRT is critical in determining potential positive or detrimental effects. Newer progestins, such as dydrogesterone, show effects that are remarkably different from those of other agents; these actions might be particularly relevant in the central nervous system and the cardiovascular system. The aim of the present paper is to review the comparative effects of dydrogesterone and other progestins at these sites, supporting the idea that the progestin has to be clinically selected
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