Research
J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108
The Case For Progesterone
Recent clinical trials in hormone therapy (HT) for women approaching or past menopause have been disappointing. Most women who have been taking conjugated equine estrogens combined with synthetic progestins have been encouraged to stop these supplements because of increased health risks. The results of the clinical trials may be accurate about the risks associated with the synthetic compounds and combinations, but the data do not reflect what might have been the case if 17beta-estradiol had been tested with natural progesterone instead of synthetic medroxyprogesterone acetate. For the most part, in almost all work on HT, estrogens have been given the primary focus despite the fact that progesterone has important properties that can enhance the repair of neurodegenerative and traumatic injuries to the central nervous system. This article reviews some of those properties and discusses the evidence suggesting that, if HT is to be reconsidered, progesterone should be given more attention as a potent neurotrophic agent that may play an important role in reducing or preventing motor, cognitive, and sensory impairments that can accompany senescence in both males and females.
Psychoneuroendocrinology. 2003 Feb; 28(2):139-68
Role Of Progesterone And Other Neuroactive Steroids In Anxiety Disorders
It remains unexplained why a greater prevalence of anxiety disorders exists in women than in men, and how female hormone-related events (i.e., menstrual cycle and postpartum) can influence the course of anxiety disorders. It would appear logical that female hormones and their derivatives play a major role in these observations. The abundance of preclinical data demonstrating a role for sex hormones and their derivatives in anxiety-like behavior is in contrast to the relative paucity of experimental clinical data on the role of female hormones and neuroactive steroids in anxiety disorders. There is a dramatic potential for therapeutic anxiolytic activity of pharmacological compounds derived from powerful anxiolytic agents, such as the progesterone derivative, allopregnanolone. As a result, there is currently tremendous interest from the pharmaceutical industry in developing and testing such agents in anxiety disorders.
Expert Rev Neurother. 2004 Sep;4(5):851-60
Differential Regulation Of Glucose Transporter Expression By Estrogen And Progesterone In Ishikawa Endometrial Cancer Cells
Estrogen replacement therapy and other unopposed estrogen treatments increase the incidence of endometrial abnormalities, including cancer. However, this effect is counteracted by the co-administration of progesterone. In the endometrium, glucose transporter (GLUT) expression and glucose transport are known to fluctuate throughout the menstrual cycle. Here, we determined the effect of estrogen and progesterone on the expression of GLUT1-4 and on the transport of deoxyglucose in Ishikawa endometrial cancer cells. Cells were incubated with estrogen, progesterone or combined estrogen and progesterone for 24 h and the effect on the expression of GLUT1-4 and on deoxyglucose transport was determined. We show that GLUT1 expression is upregulated by estrogen and progesterone individually, but that combined estrogen and progesterone treatment reverses this increase. Hormonal treatments do not affect GLUT2, GLUT3 or GLUT4 expression. Transport studies demonstrate that estrogen increases deoxyglucose transport at Michaelis-Menten constants (Kms) corresponding to GLUT1/4, an effect which disappears when progesterone is added concomitantly. These data demonstrate that different hormonal treatments differentially regulate GLUT expression and glucose transport in this endometrial cancer cell line. This regulation mirrors the role played by estrogen and progesterone on the incidence of cancer in this tissue and suggests that GLUT1 may be utilized by endometrial cancer cells to fuel their demand for increased energy requirement.
J Endocrinol. 2004 Sep;182(3):467-78
Testosterone Replacement-Induced Hyperprolactinaemia: Case Report And Review Of The Literature
Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone- replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.
Obstet Gynecol 1999 Aug;94(2):225-8
Effects Of Acute Administration Of Natural Progesterone On Peripheral Vascular Responsiveness In Healthy Postmenopausal Women
Peripheral vascular responses to acute administration of natural progesterone were studied in 12 postmenopausal women (mean +/- SD age 50.3 +/- 4.8 years) with no evidence of cardiovascular disease. According to a randomized, double-blind protocol, all subjects were given natural progesterone as a vaginal cream, able to produce a rapid peak and decay of plasma hormone concentrations, or matched placebo, with crossover after a one-week washout period. Forearm blood flow and peak flow after ischemic stress (ml/100 ml/min), local vascular resistance (mm Hg/ml/100 ml/min), venous volume (ml/100 ml), and venous compliance (ml/100 ml/mm Hg) were measured by strain-gauge venous occlusion plethysmography at baseline and after progesterone or placebo administration. Plasma norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection. Progesterone sharply decreased forearm blood flow (p amp;lt;0.01) through an increase in local vascular resistance (p amp;lt;0.01). Measures of venous function remained unchanged. Although the hormone increased circulating norepinephrine concentrations (p amp;lt;0.05), there were no significant changes in mean arterial pressure or heart rate. Furthermore, progesterone reduced the local vasodilator capacity, shown by a decrease in forearm delta flow (difference between peak flow and basal flow, p amp;lt;0.05). Compared with the well-known effect of estrogen, progesterone exerted an opposite action on peripheral vascular responsiveness. Peripheral circulatory changes may be attributed to a direct activity of progesterone on the arterial wall and may in part reflect a modulation of the hormone on peripheral sympathetic tone. Consideration must be given to the hypothesis that the addition of progestin may attenuate the beneficial effects of unopposed estrogen replacement therapy in postmenopausal women.
Am J Cardiol 1999 Jul 15;84(2):214-8
Effects Of Estrogen And Progesterone On Age-Related Changes In Arteries Of Postmenopausal Women.
1. Hormone replacement therapy (HRT) with estrogen or estrogen plus progestin may have different effects on
arterial structure and function. To examine this question, carotid artery intima-medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with estrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was reduced and high-density lipoprotein-cholesterol was increased in the HRT group compared with the non-HRT group; low-density lipoprotein-cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age; SAC was higher in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group showed increased carotid stiffness compared with the HRT-E group. 6. There is an apparent protective effect of long-term estrogen therapy on carotid IMT and age-related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.
