Treatment Of Postmenopausal Symptoms Research Articles

Effects of Artemisia annua L. on postmenopausal syndrome in ovariectomized mice

Ethnopharmacological relevanceArtemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to treat symptoms caused by deficiency of Yin, which might be observed in menopausal state from the point of view of traditional medicine. Aim of the studyWe hypothesized that A. annua might be useful for treating menopausal disorders with less adverse effects than hormone replacement therapy. Thus, the aim of the present study was to investigate effects of A. annua on postmenopausal symptoms of ovariectomized (OVX) mice. Materials and methodsOVX mice were employed as a model for postmenopausal disorders. Mice were treated with a water extract of A. annua (EAA; 30, 100 or 300 mg/kg, p.o.) or 17β-estradiol (E2; 0.5 mg/kg, s.c.) for 8 weeks. Open field test (OFT), novel object recognition task (NOR), Y-maze test, elevated plus maze test (EPM), splash test and tail suspension test (TST) were conducted to determine whether EAA could ameliorate postmenopausal symptoms. Phosphorylated levels of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK-3β), β-catenin and expression level of synaptophysin in the cortex and hippocampus were evaluated by Western blot analysis. ResultsEAA treatment significantly increased the discrimination index in NOR, decreased the time in closed arm than in open arm in EPM, increased grooming time in splash test, and decreased immobility time in TST, as did E2 treatment. In addition, decreased phosphorylation levels of ERK, Akt, GSK-3β, and β-catenin and expression levels of synaptophysin in the cortex and hippocampus after OVX were reversed by administration of EAA and E2. ConclusionThese results suggest that A. annua can ameliorate postmenopausal symptoms such as cognitive dysfunction, anxiety, anhedonia, and depression by activating ERK, Akt, and GSK-3β/β-catenin signaling pathway and hippocampal synaptic plasticity, and that A. annua would be a novel treatment for postmenopausal symptoms.

Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice

Coumestrol, a phytoestrogen compound found in various plants, has been shown to act as a potent estrogen receptor (ER) agonist, with a higher binding affinity for ERβ than for ERα. However, there is currently limited information regarding its beneficial effects in postmenopausal disorders and its ER-mediated mechanisms. Herein, we investigated the effects of coumestrol (subcutaneous or oral treatment) on metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet, in comparison with the effects of 17β-estradiol (E2) replacement. Coumestrol was administered daily at a dose of 5 mg/kg for 10 weeks. Coumestrol treatment through the subcutaneous route stimulated uterine growth in OVX mice at a level lower than that of E2. E2 and coumestrol prevented body fat accumulation, adipocyte hypertrophy, and hepatic steatosis, and enhanced voluntary physical activity. Coumestrol showed estrogen-mimetic effects in the regulation of the protein expressions involved in browning of white fat and insulin signaling, including increased hepatic expression of fibroblast growth factor 21. Importantly, the metabolic effects of coumestrol (oral administration at 10 mg/kg for 7 weeks) were mostly abolished following co-treatment with an ERβ-selective antagonist but not with an ERα-selective antagonist, indicating that the metabolic actions of coumestrol in OVX mice are primarily mediated by ERβ. These findings provide important insights into the beneficial effects of coumestrol as a phytoestrogen supplement for the prevention and treatment of postmenopausal symptoms.

Update on hormone therapy for the management of postmenopausal women.

Hormone therapy (HT) has been used in postmenopausal women for decades in clinical practice. With further analysis and newer studies, the benefits and risks of HT have been repeatedly verified and discussed. HT is recommended for the treatment of vasomotor symptoms (VMS), genitourinary syndrome of menopause (GSM) and the prevention of osteoporosis. However, the precise association between HT and the risks of cardiovascular diseases, venous thromboembolism, neurodegenerative diseases, breast cancer, and endometrial cancer remains controversial. Therefore, determining how to take advantage of and control the risks of HT by adjusting the initiation time, regimen, and duration is crucial. Recent studies have indicated that HT is not related to the risk of all-cause, cardiovascular, or breast cancer mortality although it might increase the incidence of some chronic diseases. For symptomatic postmenopausal women under the age of 60 without contraindications, early initiation of HT is safe and probably has a mortality benefit over the long term. Initiating HT close to menopause at the lowest effective dose is more likely to have maximal benefits and the lowest risks. Transdermal and vaginal HT may have a lower risk, but recent evidence suggests additional clinical benefits of oral HT formulations in relieving VMS and preventing osteoporosis. The pooled cohort risk equation for atherosclerotic cardiovascular disease (ASCVD) and the free app named Menopro can be used to perform individual risk assessments. In addition, Chinese herbal medicines have benefits in alleviating hot flashes, depression, and menopausal symptoms, although further data are needed to strongly support their efficacy. Acupuncture and electroacupuncture have definite efficacy in the treatment of postmenopausal symptoms with few adverse effects, so they are a reasonable option as an alternative therapy for high-risk women. This review discusses the history of, guidelines on, and strategies for HT in order to make suggestions based on the most up-to-date evidence for the management of postmenopausal women.

Role of testosterone and androgen receptor in periodontal disease progression in female rats.

Sex hormone therapy has strict recommendations in the treatment of postmenopausal symptoms, in which testosterone (TES) replacement may play a potential role. However, it remains unclear whether TES affects the course of chronic inflammation and alveolar bone loss in females. Herein, we investigated the role of androgen receptor and TES on the inflammatory response and alveolar bone resorption associated with ligature-induced periodontal disease in female rats. Fifty female Holtzman rats were divided in five groups (n=10/group): androgen receptor antagonist (flutamide); estrogen receptor antagonist (fulvestrant); TES supplementation; aromatase inhibitor (anastrozole); and TES plus anastrozole. Periodontitis was induced by ligatures around the lower first molars for 2weeks. Twenty animals (n=10/group) were used as untreated ligated or non-ligated controls. Bone loss and the number of osteoclasts were measured through radiographic and immunohistochemical analysis, respectively. Inflammatory cytokines, chemokines and bone markers were measured by multiplex immunoassay and ELISA in serum samples and periodontal tissues. The blockage of androgen receptor significantly increased radiographic bone loss and tissue levels of IL-1α (P <0.05), IL-1β (P <0.001) and IL-10 (P <0.01) compared with the periodontitis group. Testosterone supplementation significantly increased EGF levels in tissue samples, whereas when combined with aromatase inhibitor anastrozole significantly increased both EGF and VEGF (P <0.05). None of the treatment conditions significantly impacted the number of osteoclasts compared with the periodontitis group. Androgen receptor activation is an important factor in the regulation of several inflammatory markers, and its blockage significantly increases bone loss.

Development of cyclodextrin hydrogels for vaginal delivery of dehydroepiandrosterone.

To develop a new vaginal delivery system for a sustained release of dehydroepiandrosterone (DHEA) in the treatment of postmenopausal symptoms, aimed to overcome the problems of poor bioavailability of the drug related to its very low water solubility. Cyclodextrin (CD)-containing hydrogels were developed, combining in a single device the hydrogel controlled release and mucoadhesion properties, and the CD solubilizing power towards DHEA. The effect of different CDs, alone or in mixtures, on the hydrogel technological and mucoadhesion characteristics was investigated. The best formulations were loaded with DHEA and characterized for loading efficiency and release properties. Hydrogels based on HPβCD/γCD (15/10%w/w) or HPβCD/HP γCD (30/20%w/w) combinations proved to be the most effective, giving ovules with the desired mechanical and mucoadhesive properties. Both formulations showed high drug loading efficiency, due to the solubilizing effect of CDs, and provided a sustained in-situ release, with a rate suitably tunable by varying the drug loaded amount and/or the CD combination. The proposed formulative strategy allowed to develop an intravaginal device with right consistency and elasticity, easy to apply, able to be retained in situ over 8 h, and to provide an effective DHEA loading and a tunable release rate.

Effect of Nigella sativa on reproductive system in experimental menopause rat model.

Menopause is the condition when regular menstrual periods cease and may be accompanied by psychological and physical symptoms. The purpose of current study was to determine Nigella sativa effects on reproductive system in experimental menopause animal models. A series of experiments was conducted to investigate the effects of different dosages of N. sativa (first experiment), various extracts of N. sativa (second experiment) and some of its ingredients (third experiment) on selected menopausal parameters of ovariectomized (OVX) rats. Forty different OVX rats were equally divided into 5 groups and administered with one of the following treatments for 21 days: conjugated equine estrogen (positive control), distilled water or olive oil (negative control), treatment groups (N. sativa300, 600 and 1200 mg/kg in the first experiment), (300mg/kg methanol, hexane and SFE extracts of N. sativa in the second experiment) and (linoleic acid 50 mg/kg, gamma linolenic acid 10mg/kg, and thymoquinone 15mg/kg in the third experiment). The results demonstrated that N.sativa exert estrogenic effect were exhibited through uterotrophic assay and vaginal cell cornification as well as blood estrogen level. Furthermore, low dose N. sativa, methanol extract and linoleic acid had prominent estrogenic like effects which were significantly different from those of control group (p<0.05) in different experiments. The finding indicated the probable beneficial role for N. sativa in the treatment of postmenopausal symptoms and possibility of using N. sativa as an alternative to hormone replacement therapy (HRT) for post menopause in human.

PIH2 - Comparison of Bazedoxifene/Conjugated Oestrogens Vs Current Therapies in the Treatment of Postmenopausal Symptoms: Systematic Review and Meta-Analysis

PIH2 - Comparison of Bazedoxifene/Conjugated Oestrogens Vs Current Therapies in the Treatment of Postmenopausal Symptoms: Systematic Review and Meta-Analysis

Profile of bazedoxifene/conjugated estrogens for the treatment of estrogen deficiency symptoms and osteoporosis in women at risk of fracture

Decreasing levels of estrogens during menopause are associated with reduced bone density and an increased risk of osteoporosis. Many women also experience bothersome vasomotor and vaginal symptoms during the menopausal transition. Results of systematic reviews and meta-analyses of randomized controlled trials have shown that both systemic estrogen therapy or hormone therapy (estrogen combined with a progestin) are useful to prevent bone loss, and they are the most effective treatment for such climacteric symptoms as hot flushes, sweating, vaginal dryness, and dyspareunia. Unfortunately, estrogen therapy and hormone therapy increase the risk of endometrial and breast cancer, respectively. The selective estrogen receptor modulators (SERMs) result in positive estrogenic effects on bone, with no negative effects on the endometrium and breast but do not provide relief from postmenopausal symptoms. The combination of a SERM with estrogen as a tissue selective estrogen complex (TSEC) is a new strategy for the prevention of bone loss and the treatment of climacteric symptoms. This combination is particularly interesting from a clinical point of view, taking into account that estrogen alone did not increase breast cancer risk by the Women’s Health Initiative. TSEC is hypothesized to provide the benefits of estrogen-alone therapy, with an improved tolerability profile because the SERM component can make possible the elimination of progestin. The objective of this review was to critically evaluate the evidence from the reports published to date on the use of bazedoxifene (a third-generation SERM) in combination with conjugated estrogens in postmenopausal women. The conclusion is that effectively, the combination of bazedoxifene and conjugated estrogens may be a promising alternative to hormone therapy for the prevention of osteoporosis and the treatment of postmenopausal symptoms in non-hysterectomized postmenopausal women.

Evaluation of estrogen-like activity of Nigella sativa in ovariectomized rats

The purpose of the current study was to evaluate estrogenic activity of Nigella sativa using ovariectomized (OVX) rats. Forty OVX rats divided into five groups. N. sativa was administered orally as a supplement to chaw palate at different doses of 300, 600 and 1200 mg/kg for 21 days to OVX rats and were compared to either positive (0.2 mg/kg conjugated equine estrogen- CEE) or negative control (1 ml distilled water). Histopathological changes of the rats’ uterus such as epithelial proliferation and endometrial glandular hyperplasia were assessed as well as uterus weight and serum estradiol level. Supplementation with N. sativa resulted in a significant increase in uterine weight as compared to the OVX controls accompanied by altering the serum estrogen levels. Histopathological evaluation of the uterine section revealed changes characterized by atrophy of the uterus in the OVX controls, while the OVX rats supplemented with N. sativa showed increased endometrial response as indicated by proliferation of the endometrial glands and epithelial hyperplasia as well as epithelial proliferation and endometrial glandular hyperplasia. The effects of N. sativa were comparable to that in the CEE group. N. sativa showed the desired effects on the physical, histological and biochemical parameters of the uterine tissue in OVX rats, thereby indicating its probable beneficial role in the treatment of postmenopausal symptoms.

Terapia de reposição hormonal e desempenho cognitivo na terceira idade

No decorrer do seu ciclo de vida, as mulheres passam por uma fase denominada climatério. A terapia de reposição hormonal é o tratamento indicado para alívio dos sintomas típicos desta fase. Recentemente, descobriu-se que a terapia de reposição hormonal pode trazer benefícios adicionais, os quais se referem a proteger as mulheres contra o declínio cognitivo associado ao envelhecimento. Este artigo aborda esta questão. Embora vários estudos indiquem que o estrógeno tem efeitos positivos sobre a cognição, os resultados reportados na literatura ainda são insuficientes para indicar a terapia de reposição hormonal para a prevenção do declínio cognitivo associado ao envelhecimento. São necessárias mais pesquisas com o intuito de elucidar os possíveis benefícios desta terapia, a influência dos hormônios no envelhecimento e outros fatores associados à menopausa e à terapia de reposição hormonal que possam também influenciar a cognição.

Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution

In spite of the fact that severe side effects have been reported, black cohosh [Actaea racemosa (syn. Cimifuga racemosa)] is likely to be one of the most popular herbs used in the treatment of postmenopausal symptoms and menstrual dysfunction. We report the cases of two patients, one with submassive liver necrosis and the other with chronic hepatitis most likely related to the use of two different preparations containing black cohosh. This represents another advice for caution concerning this popular preparation of inconsistent therapeutic value.

Benefits of hormone replacement therapy in postmenopausal women

To provide an overview of current research regarding hormone replacement therapy (HRT) and to assist healthcare providers to better educate patients about potential benefits of this therapy. A systematic review of healthcare literature was conducted with 602 articles selected from CINAHL, Medscape, Pubmed, and Medline databases. Keywords directing the search included hormone replacement therapy, benefits of hormone replacement therapy and trends, hormone replacement therapy and osteoporosis, hormone replacement, and menopause symptoms. According to the literature, HRT can assist women with postmenopausal symptoms. In addition, research shows that HRT can help some postmenopausal women with selected comorbid conditions such as osteoporosis, type II diabetes, certain cardiovascular pathologies, and colorectal cancer. The decision as to who should use any form of HRT needs to be based on the individual woman's needs, quality of life, and potential risks versus benefits. HRT has been a benefit to many women in the treatment of postmenopausal symptoms. Recent studies have shown that HRT, whether it is combined estrogen and progestin therapy, or estrogen-only therapy, can help postmenopausal women with osteoporosis and some selected comorbid conditions. Recent research indicates that some women are dying from comorbid conditions rather than breast cancer. Although the research regarding HRT in some areas may be limited, further research adds to existing knowledge and offers new ideas and possibilities in the treatment of postmenopausal symptoms and selected comorbid conditions. Certainly HRT can improve quality of life and possibly longevity for selected women. Ongoing research is needed to further validate such benefits, as well as to further explore the risks and benefits of long-term HRT. Increased knowledge about HRT will help healthcare providers better educate patients about the potential benefits of HRT, while providing documentation about who should take selected types of HRT or whether alternative treatment is preferred.

Reproductive factors and lower extremity arterial occlusive disease in women

Reproductive variables affecting sexual hormone levels seem to be significant for atherosclerosis, a major cause of morbidity of the vessels of the lower extremities such as lower extremity arterial occlusive disease (LEAOD). We quantify a direct relationship between reproductive variables including age at regular and premature menopause and the incidence of severe LEAOD among post-menopausal women. Questionnaires were administered to 269 female amputees with LEAOD, 224 patients who underwent total joint replacement due to osteoarthritis and 88 healthy women. Respondents provided information on: age at menarche, age at the onset of menopause, number of births, number of abortions, lifetime oral contraceptive use, hysterectomy, oophorectomy, and medical consultation and treatment for post-menopausal symptoms. The in-sample log-odds ratio of LEAOD incidence was modeled as a function of the reproductive variables. An increase in the risk of LEAOD was associated with a reduction in the length of the fertile period, an increase in the number of births, and lifetime oral contraceptive use of 10 years or longer; a decrease in the risk of LEAOD was associated with an increase in the number of abortions. We established a distinct relationship between reproductive variables, such as length of fertile period and age at menopause, and the development of severe LEAOD. The relations that we found are, by and large, consistent with other findings on similar ailments.

Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: A prospective, randomized trial

The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck's Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck's Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study--20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck's Depression Scale.

Human exposure to medicinal, dietary, and environmental estrogens

Estrogens are a broad class of compounds which exert many physiological effects. In addition to gonadal and peripheral endogenous estrogen production, humans can be exposed to exogenous estrogenic compounds (xenoestrogens) from medicinal, dietary and environmental sources. These compounds can exert effects similar to that of 17β-estradiol (E2) through estrogen receptor (ER)-mediated mechanisms, or via ER-independent pathways. Although estrogens are used for a number of medical purposes such as birth control and for hormone replacement therapy (HRT) in the treatment of post-menopausal symptoms, studies have found adverse health effects from their use. Increased risk of stroke and invasive breast cancer are associated with medicinal estrogen use. As an alternative to HRT, diets rich in phytoestrogens are used by many women. Even though phytoestrogen consumption is associated with reduced risk of hormone-dependent cancers and antioxidant properties, concerns about adverse effects, such as endocrine disruption, cannot be dismissed. Widespread use of chemicals with estrogenic properties in agriculture and industry has resulted in endocrine disruption in wildlife populations although the impact on human health is still in debate. In general, the ranking order of estrogen equivalent factors compared to E2 is medicinal estrogens > phytoestrogens > environmental estrogens. Serum concentrations of estrogens vary among populations depending on choice of diet, use of medicinal estrogens, and environmental exposure. Thus, determination of total exposure levels (i.e. E2 equivalent concentration) is complex and can vary greatly within a larger population.

Does tibolone exacerbate atherosclerosis?The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

This editorial refers to ‘The effect of tibolone and continuous combined conjugated equine oestrogens plus medroxyprogesterone acetate on progression of carotid intima–media thickness: the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study’ † by M.L. Bots et al., on page 746 Tibolone is widely used in many countries (though not in the USA) for the treatment of post-menopausal symptoms and to inhibit post-menopausal bone loss. Tibolone’s popularity likely reflects the observation that it equals traditional hormone therapy in the relief of hot flushes, vaginal dryness, and the prevention of bone loss and, in addition, appears to increase libido. The post-menopausal benefits of tibolone relate to the uniqueness of the metabolism of the parent molecule. In human and non-human primates, tibolone is converted to three metabolites. Two are weak estrogen agonists (the 3-alpha and 3-beta hydroxy metabolites). The third metabolite, the delta-4 isomer, is a molecule that binds both to the progesterone receptor and to the androgen receptor with progestogenic and androgenic effects. Although tibolone has numerous benefits for postmenopausal women, it markedly lowers plasma concentrations of the HDL with consistent reductions of HDL cholesterol (HDLC) and ApoA1. The magnitude of the reductions is generally 20–30%. Because there is a strong inverse relationship between both HDLC and ApoA1 and the occurrence of coronary heart disease (CHD) among women not taking hormones, there has been concern that tibolone-induced reductions in HDLC and ApoA1 might increase risk for CHD. However, recent studies have shown

Hormone replacement therapy.

An estimated 10 million women in the United States currently use hormone replacement therapy (HRT) for relief of menopausal symptoms or prevention of chronic disease conditions such as osteoporosis. 1 However, the early termination of the Women’s Health Initiative (WHI) study, which examined the use of estrogen as primary prevention for osteoporosis and other chronic conditions, has led to reevaluation of the use of exogenous estrogens. In January 2003, the United States Food and Drug Administration (FDA) revised the approved indications for estrogen alone or in combination therapy to include treatment of postmenopausal symptoms or prevention of osteoporosis, stating, “when these products are being prescribed solely for the prevention of postmenopausal osteoporosis…estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.” 1 The FDA recommended prescribing nonestrogen therapies (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, parathyroid hormone) for the treatment and prevention of osteoporosis in lower risk patients and advises use of estrogen therapy at the lowest dose for the shortest duration possible. 1

Endometrial safety and tolerability of AERODIOL® (intranasal estradiol) for 1 year

Objective: the purpose of this study was to assess the endometrial safety and patient acceptability of a pulsed estrogen therapy provided by S21400 (intranasal 17 β-estradiol) in the treatment of postmenopausal symptoms. Design: postmenopausal women ( n=408) entered an open-label, community based, multicentre trial. Patients received S21400 plus sequential (>90% of patients) or continuous progestogen. Treatment was initiated with a standard daily dose of 300 μg but dose adaptation was possible every 3 months from 150 to 600 μg daily. Endometrial biopsies were performed at entry and at 12 months, and bleeding patterns were recorded at 3-monthly intervals throughout the trial. Results: 71% of patients received 300 μg per day S21400 throughout the study, 3% had their dose decreased, 19% had their dose increased and 7% had their dose both decreased and increased. Three hundred and eleven biopsies were obtained after 12 months of treatment, there were no cases of endometrial hyperplasia. The 95% confidence interval [CI] for the rate of incidence was 0–1.2%. Cyclical bleeding occurred in 82% of sequential treatment cycles. Unexpected bleeding occurred in 5% of the treatment cycles. Presence of unexpected bleeding varied according to the treatment regimen, 15 and 4% of the cycles with combined continuous and sequential regimen, respectively. Unexpected bleeding was mostly spotting. Nasal treatment was well accepted. Nasal symptoms (itching sensation, rhinorrhea and sneezing) were mostly mild in intensity and they led to treatment withdrawal in approximately 3% of patients. The rate of treatment continuation was 85% at 1 year. Conclusions: S21400, in combination with continuous or sequential progestogen, exhibits good endometrial safety and patient acceptability in postmenopausal women.

Efficacy and acceptability of intranasal 17 β-oestradiol for menopausal symptoms: randomised dose-response study

The benefit of oestrogen therapy for menopause symptoms is well recognised. However, the means of delivery currently available have disadvantages, including variable bioavailability, intestinal and hepatic first-pass effects, and dermatological reactions. An intranasal 17beta-oestradiol spray, S21400, which bypasses such drawbacks, has been developed. We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms. In this double-blind study, 420 postmenopausal women were randomly allocated to receive intranasal placebo or S21400 in doses of 100 microg, 200 microg, 300 microg, or 400 microg, or oral oestradiol valerate in doses of 1 mg or 2 mg, daily for 12 weeks. The primary outcomes were the Kupperman Index (KI) and the incidence of hot flushes. Tolerability assessments included rhinoscopy and ciliary function tests. S21400 dose-dependently decreased KI (p<0.001), with a lowest effective dose of 300 microg/day at 4 weeks (p<0.05) and 200 microg/day at 12 weeks (p<0.01). The incidence of hot flushes decreased by a maximum of 75% (S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks). S21400 increased serum oestradiol exposure dose-dependently, to concentrations similar to those achieved with oral oestradiol 1-2 mg, with lower intra-patient and inter-patient variability. There was no significant difference in ear, nose, and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups, except for a greater incidence of sneezing and application site reaction (99% mild or moderate) in the S21400 groups. S21400 was thought to be effective and convenient by the patients, and compliance was high. Intranasally administered 17beta-oestradiol is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated. Intranasal administration avoids first-pass metabolism and provides a reproducible, easily adjustable dosing mechanism that represents a new option for hormone replacement therapy.

A Nasal 17 β-estradiol Spray (S21400-AERODIOL) Is at Least as Equivalent in Efficacy as Oral Estradiol in the Treatment of Postmenopausal Symptoms

A Nasal 17 β-estradiol Spray (S21400-AERODIOL) Is at Least as Equivalent in Efficacy as Oral Estradiol in the Treatment of Postmenopausal Symptoms