Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

The 2023 nonhormone therapy position statement of The North American Menopause Society.

OBJECTIVE: To update the evidence-based Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society. METHODS: An advisory panel of clinicians and research experts in women's health were selected to review and evaluate the literature published since the Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society. Topics were divided into five sections for ease of review: lifestyle; mind-body techniques; prescription therapies; dietary supplements; and acupuncture, other treatments, and technologies. The panel assessed the most current and available literature to determine whether to recommend or not recommend use based on these levels of evidence: Level I, good and consistent scientific evidence; Level II, limited or inconsistent scientific evidence, and Level III, consensus and expert opinion. RESULTS: Evidence-based review of the literature resulted in several nonhormone options for the treatment of vasomotor symptoms. Recommended: Cognitive-behavioral therapy, clinical hypnosis, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors, gabapentin, fezolinetant (Level I); oxybutynin (Levels I-II); weight loss, stellate ganglion block (Levels II-III). Not recommended: Paced respiration (Level I); supplements/herbal remedies (Levels I-II); cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, suvorexant, soy foods and soy extracts, soy metabolite equol, cannabinoids, acupuncture, calibration of neural oscillations (Level II); chiropractic interventions, clonidine; (Levels I-III); dietary modification and pregabalin (Level III). CONCLUSION: Hormone therapy remains the most effective treatment for vasomotor symptoms and should be considered in menopausal women within 10 years of their final menstrual periods. For women who are not good candidates for hormone therapy because of contraindications (eg, estrogen-dependent cancers or cardiovascular disease) or personal preference, it is important for healthcare professionals to be well informed about nonhormone treatment options for reducing vasomotor symptoms that are supported by the evidence.

Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.

AIM: The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT). MATERIALS AND METHODS: Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence. SUMMARY RECOMMENDATIONS: The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).

Apigenin acts as a partial agonist action at estrogen receptors in vivo.

The flavone apigenin is widely distributed in vegetables and fruits and has a variety of pharmacological effects. However, there is no definitive scientific evidence that apigenin could act as a phytoestrogen and exert exerting estrogenic or antiestrogenic efficacy in vivo. Therefore, this study was established an ovariectomy (OVX) and estrogenized mouse model to evaluate the effects of apigenin on reproductive target tissues. Our data demonstrated that apigenin could exert a double-directional adjusting estrogenic effect in vivo. Specifically, treatment with apigenin reversed the weight changes caused by abnormal estrogen levels and altered the status of vaginal epithelial cells via the estrogen receptors. In addition, we found that apigenin exhibited a significant estrogenic activity, as indicated by the reversal of uterine atrophy. Apigenin treatment could also regulate the target tissue coefficient changes and estrogen disorders caused by excessive estrogen. Importantly, the administration of apigenin could upregulated the estrogen receptor (ER) α and ER ß expression as a partial agonist. Our results demonstrate that apigenin has a double directional adjusting function in different physiological environments.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

OBJECTIVE: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. DESIGN: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. SETTING: KU Leuven, Belgium. SAMPLE: Twenty-four ewes. METHODS: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. MAIN OUTCOME MEASURES: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. RESULTS: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. CONCLUSIONS: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. TWEETABLE ABSTRACT: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

17ß-Estradiol improves osteoblastic cell function through the Sirt1/NF-κB/MMP-8 pathway.

Objective: This study aims to investigate the beneficial effects of 17ß-estradiol supplementation on the function of osteoblastic cells through the Sirtuin-1/nuclear transcription factor-κB/matrix metalloproteinase-8 (Sirt1/NF-κB/MMP-8) pathway.Methods: Mouse primary osteoblasts were obtained from neonatal mouse calvaria, and the cells were treated with or without 17ß-estradiol. We first detected the effect of 17ß-estradiol on the function of osteoblastic cells. Then, the changes in estrogen receptor-α (ERα), Sirt1, NF-κB, and MMP-8 were determined after the osteoblasts were treated with 17ß-estradiol. During supplementation with 17ß-estradiol, knockdown of Sirt1 in osteoblasts was used to further measure the changes of NF-κB and MMP-8 and observe the cell function.Results: In primary osteoblastic cells, exposure to 17ß-estradiol improved cell viability and increased the levels of bone formation biomarkers, including osteocalcin, osteoprotegerin (OPG), procollagen type 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). In addition, 17ß-estradiol supplement activated ERα and Sirt1 expression and inhibited NF-κB and MMP-8 expression. Moreover, these effects induced by 17ß-estradiol were reversed by knockdown of Sirt1 in mouse primary osteoblasts.Conclusion: 17ß-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.

Primary Ovarian Insufficiency in the Prepubertal Adolescent: A Case Report.

Although there are many etiologies for delayed puberty in adolescent-aged girls, the pediatric provider should consider primary ovarian insufficiency if estradiol remains undetectable despite elevated levels of gonadotropins. Adolescent girls with this diagnosis will need holistic care from their primary care provider, focusing on both their medical and psychosocial needs. The following case study describes a 14-year-old girl who was referred to pediatric endocrinology for delayed puberty, in the setting of increased gonadotropins and undetectable estradiol. The differential diagnosis, evaluation, and management of primary ovarian insufficiency are reviewed as well as potential long-term health considerations.

Breast Reduction Following Hormonal Therapy in a Transgender Female Patient.

In male-to-female gender transition, individuals request a number of interventions, including hormonal therapy, to promote feminizing characteristics. Estrogen-based medication is prescribed to increase breast development, decrease facial hair, promote feminine adipose tissue deposition, and soften skin. Surgical breast augmentation to supplement unsatisfying breast growth after hormonal therapy is a common and well-studied course of management for such transgender patients. In a departure from convention, the authors present a case of symptomatic macromastia requiring surgical breast reduction in a transgender woman following 24 years of hormonal therapy and illicit silicone injections in multiple areas of her body, including the breasts.

Lumping, Splitting, and Treating: Therapies Are Needed for Women With Overlapping Sexual Dysfunctions.

INTRODUCTION: Phase-specific diagnoses, such as hypoactive sexual desire disorder, are the norm in sexual medicine. Epidemiologic surveys and clinical trials show the value of this structure for understanding and treating premenopausal sexual dysfunction; however, postmenopausal women have sexual dysfunction in >1 phase, for example, in desire and arousal. OBJECTIVE: To evaluate the evidence for mixed or global sexual dysfunction in women, identify associated comorbidities, and determine the best available treatment. METHODS: Literature review of epidemiologic surveys and clinical trials to quantitate overlap in sexual dysfunction and render conclusions about treatments. MAIN OUTCOME MEASURES: The main outcome measures were the Changes in Sexual Functioning Questionnaire and the Female Sexual Function Index. RESULTS: Overlap of sexual dysfunction in women is low to moderate before menopause, but it is high after menopause. Data suggest that clinical trials of postmenopausal women diagnosed with hypoactive sexual desire disorder actually entered patients with mixed or global sexual dysfunction and that benefits were pan-phasic rather than concentrated on desire. Whether local/vaginal products for the genitourinary syndrome of menopause impact all phases of sexual dysfunction is under study. Women treated for breast or gynecologic cancer or taking antidepressants also have global sexual dysfunction. Treatment options are limited but support mindfulness-based cognitive behavioral therapy and others. Other strategies include adding or switching to a serotonin 1A receptor agonist (eg, buspirone, flibanserin), a serotonin 2A receptor antagonist (eg, flibanserin, trazodone), or a norepinephrine-dopamine reuptake inhibitor (eg, bupropion). Elimination of hormonal contraception in premenopausal women and adding hormonal therapies in postmenopausal women may be necessary. CONCLUSIONS: Practitioners should be alert to overlap of sexual dysfunction in women. Focusing diagnostics and treatment on individual phases of sexual function is appropriate in premenopausal patients, but global sexual dysfunction is more likely in women taking antidepressants or cancer chemotherapy or during and after the menopausal transition. More safe, broadly effective treatments for mixed sexual dysfunction are needed for these populations of women. Pyke RE, Clayton AH. Lumping, Splitting, and Treating: Therapies Are Needed for Women With Overlapping Sexual Dysfunctions. Sex Med Rev 2019;7:551-558.

Acupuncture for patients with premature ovarian insufficiency: A systematic review protocol.

BACKGROUND: Premature ovarian insufficiency (POI) is a difficult-to-treat gynecological disorder with complex etiologies. Although acupuncture has gained increased popularity for the management of POI, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of acupuncture for patients with POI. METHODS: The following 10 databases will be searched from the publishment to July 2019: PubMed, Embase, the Web of Science, the Cochrane Central Register of Controlled Trials, 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Digital Periodicals, Chinese Biomedical Literature Database, Chinese Scientific Journal Database database), 1 Korean medical database (KoreaMed), 1 Japanese medical database (National Institute of Informatics). The primary outcomes will be the resumption of menstruation and the serum FSH levels, and the secondary outcomes include the serum Estradiol levels, anti-Mullerian hormone levels, antral follicle count, follicular growth, endometrial thickness, and adverse events. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis or a subgroup analysis will be conducted. Risk ratio for dichotomous data and mean differences or standardized mean differences for continuous data will be calculated with 95% confidence intervals using a random effects model or a fixed effects model. RESULTS: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture in treating POI. PROSPERO REGISTRATION NUMBER: CRD42019125996.

Development of a simple and rapid method for the detection of isomiroestrol in Pueraria candollei by an immunochromatographic strip test.

Pueraria candollei (P. candollei) is a traditional Thai herb widely used for estrogen replacement therapy because it contains many unique chromenes that possess potent estrogenic activity, one of which is known as isomiroestrol. Since isomiroestrol is a promising compound that is solely present in P. candollei, it can be used as an identifying marker for standardization of P. candollei. Here, we developed a lateral-flow immunochromatographic strip (ICS) test using a colloidal gold nanoparticle-conjugated anti-isomiroestrol monoclonal antibody (12C1-mAb) for the detection of isomiroestrol in plant samples and products of P. candollei. The advantages of the developed ICS over an enzyme-linked immunosorbent assay are its simplicity and rapidity, as the ICS test can be completed 15 min after dipping the strip into the analyte solution. The detectable concentration of isomiroestrol was 7.0 µg/mL. Considering the demand for the standardization of P. candollei due to concerns regarding its quality, our ICS test using isomiroestrol as an identifying marker would be effective and useful to assess the presence of isomiroestrol.

Managing overactive bladder.

Overactive bladder (OAB) is a common and distressing condition which is known to increase with age and has a significant effect on quality of life. Whilst OAB is a symptomatic diagnosis, many patients will require basic investigations prior to initiating the appropriate management. This article will review the initial clinical assessment and management of women complaining of OAB including conservative measures and drug therapy, and will also focus on the role of estrogen. In addition, the management of refractory OAB will also be discussed including more invasive strategies such as neuromodulation, Botulinum Toxin, and reconstructive surgery.

Integrative Women's Health.

This article addresses the common women's health concerns of menopause-related symptoms, premenstrual syndrome, and chronic pelvic pain. Each can be effectively addressed with an integrative approach that incorporates interventions such as pharmaceuticals, nutraceuticals, mind-body approaches, acupuncture, and lifestyle modification.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATE.

EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) Position Statement is designed to update the previous menopause clinical practice guidelines published in 2011 but does not replace them. The current document reviews new clinical trials published since then as well as new information regarding possible risks and benefits of therapies available for the treatment of menopausal symptoms. AACE reinforces the recommendations made in its previous guidelines and provides additional recommendations on the basis of new data. A summary regarding this position statement is listed below: New information available from randomized clinical trials and epidemiologic studies reported after 2011 was critically reviewed. No previous recommendations from the 2011 menopause clinical practice guidelines have been reversed or changed. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, selective estrogen-receptor modulators (SERMs), and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, SERMs, and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. New recommendations in this position statement include: 1. RECOMMENDATION: the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for cardiovascular disease, age, and time from menopause. 2. RECOMMENDATION: the use of transdermal as compared with oral estrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease. 3. RECOMMENDATION: when the use of progesterone is necessary, micronized progesterone is considered the safer alternative. 4. RECOMMENDATION: in symptomatic menopausal women who are at significant risk from the use of hormone replacement therapy, the use of selective serotonin re-uptake inhibitors and possibly other nonhormonal agents may offer significant symptom relief. 5. RECOMMENDATION: AACE does not recommend use of bioidentical hormone therapy. 6. RECOMMENDATION: AACE fully supports the recommendations of the Comité de l'Évolution des Pratiques en Oncologie regarding the management of menopause in women with breast cancer. 7. RECOMMENDATION: HRT is not recommended for the prevention of diabetes. 8. RECOMMENDATION: In women with previously diagnosed diabetes, the use of HRT should be individualized, taking in to account age, metabolic, and cardiovascular risk factors. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CAC = coronary artery calcification; CEE = conjugated equine estrogen; CEPO = Comité de l'Évolution des Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima media thickness; CVD = cardiovascular disease; FDA = Food and Drug Administration; HDL = high-density lipoprotein; HRT = hormone replacement therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL = low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI = selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI = Women's Health Initiative.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

Activity based evaluation of a traditional Ayurvedic medicinal plant: Saraca asoca (Roxb.) de Wilde flowers as estrogenic agents using ovariectomized rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Saraca asoca (Roxb.) de Wilde, Ashok, is a popular traditional plant used for gynecological disorders. In India, the juice of Ashok flowers is traditionally consumed as a tonic by women in case of uterine disorders. But despite the use, its estrogenic potency is not yet evaluated and thus lacks the scientific recognition and acclaim. AIM OF THE STUDY: This study is designed to investigate the estrogenic potential of standardized ethanolic extract of Saraca asoca flowers (SAF) using ovariectomized (OVX) female albino Wistar rat model. MATERIALS AND METHODS: Saraca asoca flowers were extracted in ethanol using hot maceration technique and the extract was standardized in terms of content of four phytoestrogens like quercetin, kaempferol, ß-sitosterol and luteolin using HPTLC technique. Safety of the extract was evaluated at a dose of 2000mg/kg body weight in female albino Wistar rats as per the OECD guidelines. Bilateral ovariectomy surgery was performed for the excision of both the ovaries. The OVX animals were treated with the ethanolic extract of SAF at three dose levels- 100mg/kg, 200mg/kg and 400mg/kg body weight in distilled water as a vehicle, orally once a day for two weeks. Estradiol valerate was employed as a modern drug for comparative evaluation of the results. Estrogenic potency was studied by assaying the activities of serum and plasma marker enzymes and hormones viz. G6PDH, LDH, 17ß-estradiol, progesterone along with cholesterol, triglycerides and HDL, and vaginal cornification. The uterotrophic effect was evaluated by studying the histoarchitecture of the uterus, effect on uterine weight and changes in the levels of uterine glycogen content. RESULTS: HPTLC revealed the presence of markers like quercetin, kaempferol, ß-sitosterol and luteolin from the ethanolic extract of SAF. The content of the four markers was found to be 1.543mg/g, 0.924mg/g, 4.481mg/g and 2.349mg/g, respectively. SAF extract was found to be safe at an oral dose of 2000mg/kg body weight in rats. Among the three doses administered to ovariectomized rats, treatment with high dose was found to be more efficacious when compared with ovariectomized rats. CONCLUSION: The findings of this study firmly support the estrogenic potency of ethanolic extract of SAF which may be by the reason of phytoestrogens.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

New aspects of postmenopausal osteoporosis treatment with micronized estradiol and progesterone.

OBJECTIVES: The aim of the study was to assess the effectiveness of postmenopausal osteoporosis treatment with natural sex hormones. MATERIAL AND METHODS: The single-blind study included 210 women, randomly allocated to three different groups, with various methods of treatment: Group I (70 controls) received transcutaneous placebo for the course of one year, Group II (70 females, aged 52.2 ± 3.1 years) used oral hormone supplementary therapy (HST), and Group III (70 females, aged 51.9 ± 3.5 years) received transcutaneous modified hormone replacement therapy (MHRT), supplemented with intravaginal lutein, dietary minerals, and 1000 IU of vitamin D3/day. RESULTS: No increase in bone mineral density was observed in the control group. However, mineral density of the vertebral bodies was significantly higher after 3 and 5 years in the HST group (p < 0.05), and after 1 year in the MHRT group (p < 0.01). This increase was even more significant (p < 0.001) after 3 and 5 years in the MHRT group. CONCLUSIONS: Transcutaneous hormone therapy with micronized estradiol and progesterone is the treatment of choice in postmenopausal osteoporosis, as evidenced by bone mineral density and biochemical markers.

Hormone Therapy and Other Treatments for Symptoms of Menopause.

The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.

Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management.

Genitourinary syndrome of menopause, a new term for a condition more renowned as atrophic vaginitis, is a hypoestrogenic condition with external genital, urological, and sexual implications that affects >50% of postmenopausal women. Due to sexual embarrassment and the sensitive nature of discussing symptoms, genitourinary syndrome of menopause is greatly underdiagnosed. The most up-to-date literature pertaining to clinical manifestations, pathophysiology, etiology, evaluation, and management of genitourinary syndrome of menopause is comprehensively reviewed. Early detection and individually tailored pharmacologic (eg, estrogen therapy, selective estrogen receptor modulator, synthetic steroid, oxytocin, and dehydroepiandrosterone) and/or nonpharmacologic (eg, laser therapies, moisturizers and lubricants, homeopathic remedies, and lifestyle modifications) treatment is paramount for not only improving quality of life but also for preventing exacerbation of symptoms in women with this condition.