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Abstract Prior to 2002, hormone replacement therapy (HRT) was considered to be an important component of postmenopausal healthcare. This was based on a plethora of basic, epidemiological and clinical studies demonstrating the health benefits of supplementation with human sex steroids. However, adverse findings from the Women's Health Initiative (WHI) studies that examined the 2 major forms of HRT in use in the US at that time - Premarin (conjugated equine estrogens; CEE) and Prempro (CEE + medroxyprogesterone acetate; MPA), cast a shadow over the use of any form of HRT. Here we review the biochemical and physiological differences between the non-human WHI study hormones – CEE and MPA, and their respective human counterparts 17β-estradiol (E 2) and progesterone (P 4). Preclinical data from the last 30 years demonstrate clear differences between human and non-human sex steroids on numerous molecular, physiological and functional parameters in brain, heart and reproductive tissue. In contrast to CEE supplementation, which is not always detrimental although certainly not as optimal as E 2 supplementation, MPA is clearly not equivalent to P 4 , having detrimental effects on cognitive, cardiac and reproductive function. Moreover, unlike P 4 , MPA is clearly antagonistic of the positive effects of E 2 and CEE on tissue function. These data indicate that minor chemical changes to human sex steroids result in physiologically distinct actions that are not optimal for tissue health and functioning. Highlights • Post-menopausal hormone replacement therapy is currently not recommended. • This recommendation is based on negative findings with the hormone replacement therapies Premarin (CEE) & Prempro (CEE+MPA). • Data indicates functional differences between non-human steroids in Premarin & Prempro compared to human sex steroids. • Preclinical data demonstrate CEE and MPA are not optimal or detrimental when compared with 17β-estradiol and progesterone. • Preclinical data indicates MPA in particular, and perhaps CEE, should be avoided for post-menopausal hormone therapy. [ABSTRACT FROM AUTHOR]

Menopause is associated with cognitive decline, and hormone therapies (HTs) may improve cognition depending on type and timing of HTs. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin 6 months later, and all rats were trained in the Morris water maze. Premarin improved early spatial learning and memory in nulliparous rats but impaired early learning in primiparous rats. With training, primiparity increased hippocampal neurogenesis, and Premarin decreased immature neurons, regardless of parity. Moreover, Premarin increased serum tumor necrosis factor α and the CXC chemokine ligand 1 (CXCL1) in trained nulliparous, but not primiparous, rats. However, Premarin decreased the expression of the immediate early gene zif268 in the dorsal CA3 region in primiparous rats after training. Thus, primiparity alters how Premarin affects spatial learning, neuronal activation, and serum cytokines. These findings have implications for the treatment of age-associated cognitive decline in women. [ABSTRACT FROM AUTHOR]

A promising alternative to conventional hormone therapy for postmenopausal symptoms is treatment combining Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), and conjugated equine estrogen (CE). This combination is also known as a tissue-selective estrogen complex (TSEC). Understanding the tissue-specific actions of SERMs and the TSEC remains a major challenge to try to predict their clinical effects. The aim of this study was to compare acute versus chronic treatment with BZA, CE or CE + BZA in two major targets of estrogens, the uterus and the liver. In these two tissues, acute treatment with CE, but not with BZA, induced similar gene expression change than the most important endogenous estrogen, 17-β estradiol (E2). Acute induction of gene expression by E2 or by CE was antagonized by the addition of BZA. Concomitantly, BZA alone or in combination with E2 or CE induced a partial degradation of ERα protein after acute exposure. In uterus, chronic treatment of BZA alone had no impact on tissue weight gain or on epithelial cell proliferation, and also antagonized CE-effect in uterus, thereby mimicking the acute effect. By contrast, in the liver, chronic BZA and CE + BZA elicited agonistic transcriptional effects similar to those of CE alone. In addition, at variance to BZA acute effect, no change in ERα protein abundance was observed after chronic treatment in this tissue. These experimental in vivo data highlight a new aspect of the time-dependent tissue–specific action of BZA or TSEC, i.e. they can act acutely as antagonists but become agonists after chronic treatment. This shift was observed in liver tissue, but not in proliferative sex target such as the uterus. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Bazedoxifene/conjugated estrogens can be used with leuprolide as effective add‐back therapy in premenopausal women with endometriosis without unwanted stimulation of the breasts, CNS (Central Nervous System), or endometrium. Bazedoxifene/conjugated estrogens may be an effective progestin‐free alternative to traditional add‐back therapies. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes. Menopause is associated with an increased risk for MetS. The purpose of this meta-analysis is to better understand the relationship between MetS and menopause.Methods: MEDLINE and EMBASE were searched for all the associated articles on (1) MetS components in postmenopausal women vs. premenopausal women, (2) comparison of MetS incidence between surgical menopause and natural menopause, (3) the effect of hormone therapy (HT) with 17β-estradiol (E2) compared to conjugated equine estrogen (CEE) on MetS components among postmenopausal women. A meta-analysis was applied by Review Manager 5.3 software.Results: All comparable indicators were significantly unfavorably changed in postmenopausal women compared to premenopausal women except for high density lipoprotein cholesterol. Women who underwent surgical menopause suffered a 1.51-fold higher risk for MetS compared to those with natural menopause. HT with E2 provided more benefits for levels of triglyceride and diastolic blood, while CEE showed a better effect on both high and low density lipoprotein cholesterol levels.Conclusions: Menopause nearly adversely affects all components of MetS, and surgical menopause may lead to a higher incidence of MetS compared to natural menopause. HT with various preparations may have different effects on MetS components. These results may clarify the management of menopause-related MetS in clinical practice. [ABSTRACT FROM AUTHOR]

The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, prasterone), conjugated equine estrogens (CEE) and estradiol (E 2 ) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E 2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E 2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with prasterone, 0.7 to 1.0 with CEE and 0.33 for the E 2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for prasterone, 1.1 unit for CEE and 1.23 unit for E 2 . The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for prasterone, 0.40 unit for CEE and 0.33 for the E 2 study with combined symptoms. Daily 6.5 mg (0.50%) prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E 2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal prasterone to compensate for the low serum concentration of prasterone observed in the majority of women after menopause without concerns about systemic effects. [ABSTRACT FROM AUTHOR]

The many advantages of registered bioidentical sex hormones over registered, conventional, non-bioidentical menopausal hormone therapy (MHT) are considered. The transdermal route of estrogen administration avoids excess venous thromboembolic and ischemic stroke events. There is some indication that conjugated equine estrogens are more thrombogenic and most likely induce some hypertensive responses; estradiol might also be superior to conjugated equine estrogens (CEE) in terms of global cardiovascular health. The most valid evidence presently suggests that CEE-only treatment does not increase the risk of breast cancer and even may reduce it. But its combination with a synthetic progestogen (mainly medroxyprogesterone acetate) is a critical issue since it seems to be primarily associated with an increased incidence of breast cancer, however similar to or lower than that associated with some common lifestyle factors. Though not yet proven in a randomized, controlled trial, MHT continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones but also than oral conventional MHT and has the best breast profile; registered products for such optimal MHT are available around the world and must be preferred. [ABSTRACT FROM PUBLISHER]

Background: Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.Methods: Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.Results: Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.Conclusions: CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years. [ABSTRACT FROM AUTHOR]

The first tissue-selective estrogen complex (TSEC), consisting of a combination of a conjugated equine estrogen (CEE) and bazedoxifene (BZA), has been approved for treatment of the menopause in the USA and European Union. We have postulated that this TSEC might block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer growth. This manuscript, representing a presentation at a Festschrift honoring Evan Simpson, reviews our published data BZA blocked the in vitro effects of both estradiol and CEE on cell growth and gene expression in MCF-7 cells. BZA completely blocked CEE- or E 2 -stimulated ductal and terminal end bud growth of immature murine mammary glands and the growth of experimental breast cancers. These findings provide a rationale for future clinical studies to determine whether this TSEC prevents the growth of occult breast cancer in women. [ABSTRACT FROM AUTHOR]

Prior to the unexpected early termination of the Women’s Health Initiative (WHI) trial of continuous conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA), the prevailing view was that hormone replacement therapy (HRT) was a low-risk intervention with immediate value for symptom relief in recently menopausal women, and that it probably conferred long-term protection against the major chronic diseases that affect women after menopause. Rather than replicating prior studies, the WHI was designed to test whether the beneficial associations consistently seen in women starting HRT near menopause would be found in women well beyond menopause. Views of the benefits and risks of HRT changed dramatically in 2002 with the unexpected early termination of the CEE + MPA trial and the alarming initial WHI report. HRT use plummeted world-wide, driven by fear of breast cancer and skepticism about cardiovascular benefits. Stunningly, the contrasting findings of the WHI trial of CEE alone reported 2 years later – suggesting prevention of coronary heart disease in women who began HRT at age <60 years, and a reduction in breast cancer overall – were largely ignored. Key lessons from the WHI are that the effects of HRT on most organ systems vary by age and time since last physiologic exposure to hormones and that there are differences between regimens. In the years since the first WHI report, we have learned much about the characteristics of women who are likely to benefit from HRT. The range of HRT regimens has also increased. Not all women have indications for HRT, but for those who do and who initiate within 10 years of menopause, benefits are both short-term (vasomotor, dyspareunia), and long-term (bone health, coronary risk reduction). Critically, the ‘facts’ that most women and clinicians consider in making the decision to use, or not use, HRT are frequently wrong or incorrectly applied. [ABSTRACT FROM PUBLISHER]

Purpose: To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms.Methodology: A randomized, single blind, four arm, parallel assignment study was conducted in VMMC and SJH, New Delhi, India. 200 Indian menopausal women were recruited and assigned into four treatment groups viz., estradiol valerate (E2V), conjugated equine estrogen (CEE), isoflavones and Placebo group. The statistical significance of categorical variables was determined by Chi-square, Fisher's exact test. In case of quantitative variable parametric test Student's t test was used. In case of quantitative variables where data are not normally distributed, Kruskal-wallis test and Wilcoxon Mann-Whitney test were used. Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups.Results: Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes. 91.9 % decrease was observed in mean hot flash score in the E2V group after 24 weeks of treatment, 89.2 % in the CEE group, 60.42 % decrease in the isoflavones group. While placebo led to 47.9 % decrease in mean hot flash score. After 24 weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group. No serious side effect was reported in any of the groups.Conclusion: Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24 weeks. However, it seems more reasonable to replenish with less costly and bio-identical hormone, i.e. micronized estradiol valerate which is equally effective.Trial Registry: The trial was registered under Clinical trial registry of India prospectively (number: CTRI/2012/04/002566). [ABSTRACT FROM AUTHOR]

Bazedoxifene ( BZA), a third-generation selective estrogen receptor modulator ( SERM), has been combined with conjugated equine estrogen ( CE) to create a tissue selective estrogen complex ( TSEC) for the management of vasomotor symptoms ( VMS) and the prevention of osteoporosis ( OP) associated with menopause. Both of these outcomes of menopause contribute to significant negative effects on quality of life and increases in utilization of health care resources and dollars. Current treatment modalities for VMS and OP include estrogen therapy that requires the use of progestin in women who have a uterus to reduce the risk of endometrial hyperplasia and resultant cancer. However, progestin use results in nuisance bleeding as well as a further increased risk of breast cancer when combined with estrogen. And while SERMs can be used to prevent OP, their use alone has been shown to increase hot flashes. The combination of BZA and CE does not require progestin treatment with CE as the BZA component acts as an antagonist on endometrial tissue. The U.S. Food and Drug Administration approval of BZA/ CE in 2013 was based on a series of five phase 3 studies known as the Selective estrogens, Menopause And Response to Therapy ( SMART) trials. These trials, in their entirety, evaluated the impact of BZA/ CE on VMS frequency and severity, bone mineral density, bone turnover markers, vaginal symptoms, lipid profiles, sleep, quality of life, breast density, and endometrial safety. The approved dose of BZA/ CE is 20 mg BZA and 0.45 mg CE. Although this TSEC manages VMS while opposing breast and endometrial proliferation, preventing bone resorption, and improving lipid profiles, long-term experience with BZA/ CE is currently lacking. [ABSTRACT FROM AUTHOR]

Background: Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17β-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain.Methods: The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire.Results: Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17β- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02).Conclusions: Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17β-estradiol in platelets and the brain. [ABSTRACT FROM AUTHOR]

The treatment of transwomen relies on the combined administration of anti-androgens or Gn RH analogues to suppress androgen production and thereby reduce male phenotypic characteristics together with oestrogens to develop female characteristics. In transwomen, synthetic oestrogens such as ethinyl oestradiol, as well as conjugated equine oestrogens ( CEE), should be avoided to minimize thromboembolic risks especially in older transwomen and in those with risk factors. Currently, available short- and long-term safety studies suggest that cross-sex hormonal therapy ( CHT) can be considered safe in transwomen improving the well-being and quality of life of these individuals. Long-term monitoring should aim to decrease cardiovascular risks and should include prostate and breast cancer screenings. [ABSTRACT FROM AUTHOR]

Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and was generally considered to be safe until the results of long-term studies of postmenopausal hormone therapy (HT) using treatment with conjugated equine estrogens (CEE) combined with MPA and CEE alone suggested that MPA, and perhaps other progestogens, may play a role in the increased risk of breast cancer and cardiovascular diseases. This review examines critically the safety of MPA in terms of breast cancer and cardiovascular disease risk, and its effects on brain function. Research into mechanisms by which MPA might cause adverse effects in these areas, combined with the available clinical evidence, suggests a small increase in relative risk for breast cancer and stroke, and a decline in cognitive function, in older women using MPA with an estrogen for postmenopausal HT. However, short-term (less than 5 years) use of MPA with an estrogen in the years immediately after the onset of menopause for the management of vasomotor symptoms does not appear to be associated with any increased risk of these disorders. [ABSTRACT FROM AUTHOR]

A need exists for the effective treatment of individuals suffering from spinal cord injury (SCI). Recent advances in the understanding of the pathophysiological mechanisms occurring in SCI have resulted in an expansion of new therapeutic targets. This review summarizes both preclinical and clinical findings investigating the mechanisms and cognate pharmacologic therapeutics targeted to modulate hypoxia, ischemia, excitotoxicity, inflammation, apoptosis, epigenetic alterations, myelin regeneration and scar remodeling. Successful modulation of these targets has been demonstrated in both preclinical and clinical studies with agents such as Oxycyte, Minocycline, Riluzole, Premarin, Cethrin, and ATI-355. The translation of these agents into clinical studies highlights the progress the field has made in the past decade. SCI proves to be a complex condition; the numerous pathophysiological mechanisms occurring at varying time points suggests that a single agent approach to the treatment of SCI may not be optimal. As the field continues to mature, the hope is that the knowledge gained from these studies will be applied to the development of an effective multi-pronged treatment strategy for SCI. [ABSTRACT FROM AUTHOR]

The Women’s Health Initiative (WHI) Estrogen-Alone Trial randomized postmenopausal women, 50 to 79 years of age, with prior hysterectomy, to conjugated equine estrogens (CEE) or placebo with a 5.9-year median duration of CEE use. In 2013, the WHI published outcomes for additional extended follow-up. Reported here for the first time is an analysis of the number needed to treat with CEE rather than placebo for younger women (50–59 years) to prevent an adverse long-term outcome. For every 76 women randomized to CEE at 50–59 years, one less myocardial infarction occurred during the 13-year cumulative long-term follow-up. For every 37 women randomized to CEE at 50–59 years, one less woman experienced a global index endpoint (including coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, hip fracture, and death) during the 13-year follow-up. Younger women (50–59 years), compared to older women, had more favorable cumulative long-term outcomes for MI and global index. Though a subgroup analysis is not an adequate basis for making primary prevention guideline recommendations, the WHI Estrogen-Alone Trial outcomes strongly suggest that a similar course of estrogen initiated at 50–59 years in postmenopausal women with prior hysterectomy results in significant long-term health benefit. [ABSTRACT FROM AUTHOR]

Animals remain an important source of drugs in the search for new medicinal compounds. Drugs from animal sources include insulin, pituitary hormones, vitamins, and antibiotics and biological agents, such as vaccines and immune serums. Insulin, discovered by Frederick Banting, was one of the earliest drugs to derive from animals. Today, a new drug called exenatide from the Gila monster's spit keeps glucose blood levels steady, as well as ensuring weight loss in many patients. Many drugs, adjuvants and cosmetic substances derive from domestic animals, as well as wild ones. Premarin and gelatine, obtained from horses, are vital to our being. Hyaluronic acid, originally found in rooster combs, is a popular skin care ingredient, as well as a medicinal agent for osteoarthritis and eye surgeries. The venom and toxin from animals, like snakes, spiders, scorpions and insects, is extremely potent because it interacts with specific macromolecular targets in the body. Thus, it has been used as the lead compound in the development of novel drugs, such as natural adhesives used in surgeries, and to help to treat strokes, digestive disorders and gastric reflux disease. It may also be useful in treating and preventing cardiovascular disease. Cytarabine, obtained from the Caribbean sponge, is used in the treatment of acute myeloid leukaemia. Many new antibiotics are being developed from alligators and frogs which spend their lives in places that are teeming with infectious microbes. [ABSTRACT FROM AUTHOR]

This Medical Letter provides 2 Tables summarizing key information about drugs for menopausal symptoms published as part of a comprehensive review on the topic. [ABSTRACT FROM AUTHOR]

Background: Embryo transfer to a developed endometrium is an important prognostic factor in frozen-thawed embryo transfer cycle outcome. Vaginal estrogen, such as Vagifem vaginal tablets and Premarin vaginal cream, is a regimen used for the patients with refractive endometria. Objective: Our objective was to compare the effects of Vagifem and Premarin on the endometrial thickness of the patients with refractive endometria. Materials and Methods: In this randomized clinical trial, 30 patients with refractive endometria in frozen-thawed embryo transfer cycles received Vagifem vaginal tablets and 30 women received Premarin vaginal cream. Endometrial thickness was measured on the 14th day of drug administration. Results: Comparing the endometrial thicknesses of the two groups showed that the endometria of the Vagifem group was significantly thicker than that of the Premarin group (5.93±0.38 vs. 6.74±0.32; p<0.001). Conclusion: Vagifem is superior to Premarin in induction of endometrial thickness in frozen-thawed embryo transfer cycles in the patients with refractive endometria. [ABSTRACT FROM AUTHOR]

Abstract: Estrogens have been implicated as possible therapeutic agents for improving cognition in postmenopausal women and have been linked to neurodegenerative disorders such as Alzheimer''s disease. However, the utility of Premarin (Wyeth Pharmaceuticals, Markham, ON, Canada), a conjugated equine estrogen and the most commonly prescribed hormone therapy, has recently been questioned. The purpose of this study was to investigate the effects of Premarin at 2 different doses (10 or 20 μg) on hippocampus-dependent spatial learning and memory, hippocampal neurogenesis, and new neuronal activation using a rodent model of surgical menopause. Rats were treated daily with subcutaneous injections of Premarin and trained on the spatial working/reference memory version of the radial arm maze. Premarin impaired spatial reference and working learning and memory, increased hippocampal neurogenesis, but either decreased or increased activation of new neurons in response to memory retrieval as indexed by the expression of the immediate early gene product zif268, depending on the maturity of cells examined. This activation of new neurons was related to impaired performance in Premarin-treated but not control-treated female rats. These results indicate that Premarin may be impairing hippocampus-dependent learning and memory by negatively altering the neurogenic environment in the dentate gyrus thus disrupting normal activity of new neurons. [Copyright &y& Elsevier]

Objective: To measure skin wrinkles and rigidity in menopausal women of varying race/ethnicity with or without hormone therapy (HT) for up to four years.Design: Randomized, double-blind, placebo-controlled trial.Setting: Academic medical centers.Patient(s): Women (42-58 years of age) within 36 months of last menstrual period and enrolled in the Kronos Early Estrogen Prevention Study (KEEPS).Intervention(s): Treatment with 0.45 mg oral conjugated equine estrogens (CEE), transdermal E2 (50 μg/d) with micronized P (200 mg daily), or placebo for 4 years.Main Outcome Measure(s): Skin wrinkles were assessed at 11 locations on the face and neck, and skin rigidity was assessed at the forehead and cheek at baseline and yearly for 4 years.Result(s): Neither total wrinkle score nor total rigidity score was significantly different at baseline or over the 4-year follow-up among patients randomized to CEE, E2, or placebo. Skin wrinkle and rigidity scores were primarily affected by race/ethnicity, with scores being significantly different between races for almost all of the wrinkle parameters and for all of the rigidity measures. There was no association between race and response to HT for total wrinkle or rigidity scores. Black women had the lowest wrinkle scores compared with white women across all 4 years. In general, skin rigidity decreased in all groups over time, but black women had significantly reduced total facial rigidity compared with white women after 4 years.Conclusion(s): Race is the strongest predictor of the advancement of skin aging in the 4 years following menopause. HT does not appear to affect skin wrinkles or rigidity at most facial locations.Clinical Trial Registration Number: NCT00154180. [ABSTRACT FROM AUTHOR]

A chart is presented that lists several therapeutics for hormone replacement such as oral estrogen, transdermal estrogen and vaginal estrogen characterized according to its generic name, strength and dosing frequency including Premarin, Estrogel and Combipatch.

The article evaluates several generic drug brands including Premarin, Alora and Provera in terms of their strength and dosage forms for use in hormone replacement therapies.

The article evaluates several drugs for hormone replacement containing estrogen including the Premarin, norethindrone acetate and estropipate.

The article offers brief information on several therapeutic drugs used for hormone replacement which include the estradiol from brand Femtrace, the conjugated estrogen from brand Premarin, the progestrerone from brand Prometrium.