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Katz, M. Ranga R. Krishnan, M. Alfred J. Lewy, M. Steven E. Lindley, M. Peter T. Loosen, M. Bruce S. McEwen, Ph. David Michelson, M. Dominique L. Musselman, M. D Charles B. Nemeroff, M. David O'Connor, M. Harrison G. Pope Jr. Victor I. Reus, M. Magda Rittenbaum, M. Anthony J. Rothschild, M. David R. Rubinow, M. Robert L. Sack, M. Alan F. Schatzberg, M. Peter J. Schmidt, M. Stephen Sokolov, M. Monica N. Starkman, M. Martin Szuba, M.

Steven J. Wamback, B. Lisa S. Weinstock, M. Peter Whybrow, M. Owen M. Wolkowitz, M. He was awarded the Curt P. Richter Prize in by the International Society of Psychoneuroendocrinology for his contributions to the field. I Accept. Description The mind-body connection is one of the hottest topics in medicine today, documented by enormous amounts of data regarding hormone effects on the brain and behavior.

Write a review Name. Custom-compounded hormone therapies have become increasingly popular but are not recommended because the manufacturing process lacks FDA oversight Clinical trials documenting the efficacy and safety of compounded progesterone for endometrial protection are lacking. Proponents of custom-compounded hormone therapies often advise measuring salivary hormone levels to monitor therapy. However, scientific evidence is lacking to justify salivary measurements due to inter- and intra-assay variability, variable salivary flow rates dependent upon hydration, food intake, and other factors, and the inability to predict the pharmacokinetics of a custom-compounded hormone dose in a manner that would allow for valid salivary sampling.

Bone loss at the lumbar spine and hip was prevented in postmenopausal women at risk for osteoporosis , as reflected by reduction of serum bone turnover markers and enhancement of bone mineral density vs placebo , Fracture data are lacking. Treating postmenopausal women ages 40 to 65 with VVA at baseline improved vaginal maturation at 12 weeks Women reported a lower incidence of dyspareunia.

Secondary endpoints included improvements in sleep, health-related QOL, and improved treatment satisfaction , In trials up to 2 years, the rates of breast cancer reported as adverse events, not clinical outcomes were not sufficient to assess risk or benefit , At 2 years, the incidence of neither endometrial hyperplasia nor endometrial cancer was increased , In trials of up to 2 years in women ages 40 to 65, rates of cardiovascular events, cancers breast, endometrial, ovarian , and mortality were similar to placebo , but studies were underpowered to draw firm conclusions regarding these endpoints.

Tibolone belongs to the group of normethyltestosterone progestogen derivatives and has metabolites that exhibit estrogenic, progestogenic, and androgenic effects This agent is available in many countries outside of the United States at doses of 1. Tibolone also improves sleep, mood, and urogenital atrophy and may improve libido — There is no endometrial thickening or increase in myoma with tibolone In an observational study , tibolone did not increase the risk of thrombosis.

In an RCT of older women with osteoporosis, tibolone increased stroke An RCT of women with a history of breast cancer, after a median follow-up of 3. The study reported the greatest increase for women taking an aromatase inhibitor HR, 2. Most published recommendations suggest using MHT for the shortest duration possible, but strong evidence is lacking to support this recommendation.

Current proposed limits on duration of therapy are informed by large intervention trials 5 to 7 y with extended follow-up for 13 years Regarding duration of use, these data suggest that risk rates for breast cancer and CVD increase with age and time since menopause, although the risks with ET appear to be less than with EPT.

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Ovarian cancer risk may also increase relative to duration of MHT We conclude, and guidelines from other societies concur, that clinicians and patients should reassess MHT continuation yearly and discuss the risks and individual benefits beyond 5 years 55 , Patients likely to consider continuing therapy include those who fail an attempt to stop EPT, who are at high risk for fracture, or for whom alternative therapies are not appropriate. A number of studies have compared methods ie, taper protocols vs abrupt cessation to facilitate the discontinuation of MHT — and have detected no differences.

Therefore, the approach to discontinuation is an individual choice. Anecdotally, some women find that a very low dose of ET maintains adequate symptom relief and well-being and prefer that to complete discontinuation.

Psychoneuroendocrinology The Scientific Basis of Clinical Practice

Menopausal symptoms and joint pain can recur when MHT is discontinued Depending on the severity of the symptoms, women may elect to restart MHT, perhaps at a lower dose, or seek relief with nonhormonal therapies. Accelerated bone loss was reported after the discontinuation of MHT, whereas in contrast, bone density is stable for some years after discontinuing bisphosphonate therapy.

Bisphosphonates, however, remain in bone indefinitely, and most expert groups do not recommend initiating bisphosphonate therapy for osteoporosis prevention in women aged 50 to Adverse effects such as osteonecrosis of the jaw and atypical femur fractures, while rare, increase with the duration of therapy. Furthermore, as opposed to reports from observational studies , in the long-term follow-up of the WHI, hip fracture rates did not increase during 5 to 7 years of observation after MHT was discontinued A large meta-analysis of observational studies found a persistent risk of ovarian cancer up to a decade after discontinuing MHT Urinary incontinence persisted after oral MHT was discontinued; however, the percentage of affected women was approximately one-third less than during active treatment As hot flashes result from alterations of the thermoregulatory neutral zone, shedding layers of clothing, using fans, keeping the bedroom cool 30 , avoiding alcohol and spicy foods, and reducing stress may be effective.

Being overweight or obese is a risk factor for VMS 26 , , , and weight loss may reduce hot flash frequency , The interpretation of hot flash efficacy studies requires an appreciation of an important confounding factor. Other agents such as sertraline and fluoxetine are associated with non-statistically significant trends toward the reduction of hot flashes and inconsistent results — Hot flash frequency and composite score with nonhormonal prescription therapies for relief of VMS. Upper panel, Effect on frequency of VMS; lower panel, effect on composite score severity times frequency; best representation of effect ; open bars, placebo; colored bars, therapies; length of bars, ranges in studies; horizontal bar, means.

All of these agents are generally well tolerated Hypersensitivity or prior adverse drug reactions to each of these agents represent contraindications. These agents uncommonly induce suicidal thoughts within the first few months of treatment. Preliminary evidence suggests a possible increase in risk of bone fracture.

Gabapentin and pregabalin may increase suicidal thoughts and behaviors, cause drowsiness or dizziness, and impair balance and coordination. Pregabalin may impair memory and concentration. Clonidine is contraindicated in patients with low blood pressure and may cause lightheadedness, hypotension, headache, and constipation; sudden cessation of treatment can be associated with significant increments in blood pressure Meta-analyses and a Cochrane review concluded that SSRIs and SNRIs exert mild-to-moderate effects to reduce hot flashes in women with a history of breast cancer , — Each of these agents appears to have similar efficacy in breast cancer survivors as in healthy menopausal women, although studies are small , , — Caution is advised in the use of paroxetine in patients taking tamoxifen because paroxetine markedly interferes with the metabolism of tamoxifen to its metabolite, endoxifen , , , — The only FDA-approved agent in this class is low-dose paroxetine mesylate, but others have been used off-label in the United States.

No direct trials are available to determine the relative efficacy of one over another. We describe suggested daily doses, efficacy, side effects, and contraindications in Figure 4. In general, the evidence suggests that these agents are effective and well tolerated. Four RCTs confirmed moderate efficacy in relieving hot flashes — On the basis of clinical experience, women whose hot flashes occur primarily at night respond well to a single bedtime dose.

Individual dose requirements vary widely, as determined by empiric dose escalation, and range from to mg. Gabapentin effects as a sedative and a reducer of vasomotor instability work well together when used at bedtime because sedating side effects dissipate by morning. However, when used during the day, gabapentin may result in a level of lethargy that is not tolerable.

The quality of this comparative evidence is low due to imprecision. A limited number of head-to-head RCTs have compared varying estrogen doses, preparations, and routes of administration with nonhormonal agents , , None of the RCTs established statistically significant superiority of one treatment regimen over another. However, when these and other published data are taken into account , , , , the limited evidence available suggests that standard-dose MHT is more effective than nonhormonal agents.

Clonidine transdermal patches are preferred over tablets because of more stable blood levels. Clinical trials with these agents have reported inconsistent efficacy over placebo, but individual patients may experience benefit Table 9. In a randomized trial of symptomatic menopausal women, clinical hypnosis was associated with a The phytoestrogens are nonsteroidal compounds that have both estrogenic and antiestrogenic properties. Caution is advised because some of these agents, when consumed as supplements, can exert estrogenic effects, a concern in breast cancer survivors although dietary soy appears to have no adverse effects on breast cancer prognosis Vaginal moisturizers eg, polycarbophil-based moisturizer, hyaluronic acid-based preparations, and a pectin-based preparation , when used regularly at least twice weekly , may provide an effective nonhormonal approach to alleviating symptoms of vaginal atrophy.

However, studies have been small, mostly open-labeled, and limited to 12 weeks — Although helpful, these approaches are not likely as effective as vaginal ET.

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Vaginal moisturizers have not been shown to reduce urinary tract symptoms or asymptomatic bacteriuria. Use of a vaginal moisturizer may not eliminate the need for a vaginal lubricant during intercourse. Vaginal lubricants are used to enhance the sexual experience in women with symptoms of VVA by alleviating vaginal dryness and preventing dyspareunia Lubricants do not treat the underlying problem and only briefly alleviate symptoms.

Several OTC options are available. Because data do not demonstrate the superiority of one to another, women can experiment with these products. Olive oil is also effective Petroleum jelly has been associated with an increased rate of bacterial vaginosis A Cochrane meta-analysis of vaginal estrogens compared 19 efficacy trials and found that all products effectively alleviated symptoms, but study differences limited comparisons among agents.

As a guiding principle, we recommend using the lowest effective dose. RCTs of low-dose vaginal estrogen products — report rapid improvement of vaginal symptoms vaginal dryness or dyspareunia and urinary symptoms dysuria and urge incontinence within 2 to 3 weeks. Objective improvements continue at 12 weeks and are maintained to 1 year. Limited evidence suggests that vaginal ET may prevent recurrent urinary tract infections , and overactive bladder , No clear proof exists that vaginal ET prevents or improves pelvic prolapse , but it may be advantageous preoperatively Adverse effects include potential transfer to partner via penile or oral absorption and, with vaginal creams, residue on undergarments.

Vaginal estrogen preparations have been categorized as: 1 low, 2 intermediate, and 3 systemic doses Table By using the lowest effective doses, systemic absorption is minimized. During the initiation of therapy, vaginal atrophy may enhance systemic absorption, although not all studies demonstrate this effect , When vaginal epithelium is restored after several weeks of ET , systemic absorption may decrease , Low-dose vaginal rings result in estradiol levels that remain within the normal postmenopausal range; however, bone resorption and lipid levels decrease, suggesting possible systemic effects , Insertion and removal at 3-month intervals may be difficult, the ring can be sensed during intercourse, and it can be expelled, particularly in women who have undergone a hysterectomy Therapy is initiated with daily administration for 2 weeks, and then twice weekly thereafter.

Vaginal placement of the tablet may provide less introital benefit than creams. This is a low-dose estrogen used outside the United States. Evidence is limited to studies of poor quality and very few RCTs Intermediate-dose estradiol and CEE creams provide flexibility of dosing, allow treatment from the introitus to the vaginal apex, and provide the emollient effect of vehicle.

Some systemic absorption exists , CEE 0. No RCT data are available regarding the FDA-approved dosing of estradiol 2- to 4-g vaginal cream, administered daily for 1 to 2 weeks, followed by a maintenance dosage of 1 g, one to three times a week. Estriol vaginal preparations gels and suppositories are manufactured and government regulated in a number of countries outside the United States. Estriol is considered a low-affinity estrogen and, despite increased plasma concentration after repeated vaginal administration, is not considered to have substantial systemic effects , Because serum estradiol levels during therapy usually fall within the normal postmenopausal range, the risk profile with low-dose vaginal ET is expected to be lower than with systemic ET However, long-term endometrial safety data are lacking, and 1 year is the maximum duration of RCTs of vaginal ET Side effects include vulvovaginal candidiasis , and, with higher dosing and systemic absorption, vaginal bleeding and breast pain This may reflect an actual neutral effect due to the absence of a first-pass hepatic effect by vaginal estrogens, or that studies of women at high CVD or VTE risk are lacking Available evidence does not support the boxed warning on low-dose vaginal estrogen regarding an increased risk of CHD, stroke, VTE, dementia, and breast cancer, and efforts to modify the labeling of these products are in progress Whether small increases in circulating estrogens from low-dose vaginal estrogen can stimulate the growth of residual breast cancer cells , — remains an unanswered question.

In a cohort case-control study of 13 breast cancer survivors taking adjuvant tamoxifen or aromatase inhibitor therapy for at least 1 year, after 3. These data are insufficient, however, to conclude safety and to recommend this approach. The effect of low-dose vaginal ET on endometrial cancer recurrence is unknown.

The only RCT attempting to evaluate the effect of systemic ET on recurrence rate and survival in women after surgery for stage I or II endometrial cancer was closed prematurely without complete enrollment In the absence of RCT findings to guide practice recommendations, the decision to use ET remains controversial and involves assessing the severity of postmenopausal symptoms and tumor characteristics , Raloxifene has neutral vaginal effects — In two clinical trials, vaginal, but not oral ET, was safely used to treat vaginal symptoms in women taking raloxifene without untoward endometrial effects , Bleeding or spotting in a woman using only vaginal estrogens is uncommon in the absence of endometrial pathology.

The Cochrane review of 19 studies found no significant difference among vaginal creams, tablets, or rings in terms of endometrial thickness or hyperplasia or in the proportion of women with adverse events Recent 1-year-long studies of vaginal CEE cream and low-dose vaginal estradiol tablets revealed no cases of endometrial hyperplasia or cancer as determined by endometrial biopsy , , Vaginal administration of estradiol tablets, when placed in the upper third of the vagina, may result in a uterine first-pass effect resulting in a higher degree of uterine stimulation — For women at higher risk of endometrial cancer, surveillance using transvaginal ultrasound, followed by endometrial biopsy if endometrial thickening is present, may be prudent.

Intermittent possibly annual progestogen withdrawal may be considered to assess endometrial status , Not all women are comfortable using vaginal ET, and women may prefer an oral medication specifically indicated for dyspareunia. Two week RCTs of ospemifene reported improvements in pH and vaginal maturation index, severity of dyspareunia , , and standardized measures of sexual function including desire, arousal, orgasm, and satisfaction Two year-long studies , demonstrated sustained vaginal benefits.

The most common adverse effect was VMS 7. Ospemifene involves risk of VTE and is contraindicated in women at risk for venous or arterial thrombosis or stroke. In safety studies, incidence rates for thromboembolic stroke, hemorrhagic stroke, and DVT were 0. No cases of endometrial carcinoma have been reported. The incidence of proliferative endometrium weakly plus active plus disordered was The incidence of uterine polyps was 5. Data on breast density or breast cancer risk are lacking.

Estrogen-dependent neoplasia is a contraindication. There are numerous gaps in our knowledge regarding menopause symptoms. Some of these include a lack of the most basic understanding of what causes hot flashes, questions regarding the potential link between VMS and CVD in older vs younger postmenopausal women, and a poor understanding of the relationships between menopause and sleep and hormonal transitions and mood, which have significant social and economic implications. Given the uncertainties regarding the precise neuroendocrine events that cause VMS, developing specific targeted therapies is challenging.

Establishing appropriate animal models and expanding recent research involving the neuroregulators kisspeptin, neurokinin B, and dynorphin may help develop new effective treatments Management of the transition to menopause remains uncharted territory. The SWAN and the Melbourne Women's Midlife Health Project provide extensive epidemiological, physiological, and descriptive data characterizing reproductive changes that occur during the transition to menopause.

However, clinical management decisions are often based on the extrapolation of observational data collected from studies conducted in younger, reproductive age women. RCTs of frequently prescribed therapies, such as oral contraceptives, MHT, and measures to control mood, with clinical outcomes relevant to women of relatively advanced age are sorely needed to confidently advise patients regarding the safest and most effective therapies to use during this transition. Managing the loss of ovarian function in premenopausal women due to surgery, the range of disorders manifesting as POI, or the sequelae of treatment for breast cancer and other malignancies remains challenging.

This is due to a dearth of quality data assessing the long-term risks and benefits of MHT or other options for symptom relief and prevention of chronic diseases in these groups. Fertility issues can be managed with modern assisted reproductive technology, but we fall short on adequately managing estrogen deficiency. Pressing questions remain regarding optimal treatment preparation, dosing and regimens, and the merits of long-term MHT, even in women without menopausal symptoms. International registries and clinical trials are overdue to address the long-reaching implications of these important issues.

The most persistent question for naturally postmenopausal women is how to balance menopausal symptom relief with the prevention of chronic diseases of aging such as CHD, osteoporotic fractures, and dementia. ET has long been hypothesized to meet this goal, although conclusive evidence remains elusive, and questions persist regarding the interaction between EPT and these outcomes, as well as breast cancer. Observational data suggesting differences in VTE risk and other CVD outcomes continue to accumulate, suggesting a significant need for adequately powered clinical trials comparing the safety and efficacy of oral with transdermal therapies in younger, recently postmenopausal women.

Stuenkel, MD. Susan R. Hassan Murad, M. JoAnn V. Richard J. Disclosures prior to this time period are archived. Special thanks are extended to Drs. David F. Archer, Gloria A. Bachmann, Henry Burger, Roger A. Lobo, Charles L. Loprinzi, JoAnn E. Manson, Kathryn A.

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  8. Watts for careful review and thoughtful suggestions. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Summary of Recommendations. Introduction and background. Future research. Oxford Academic. Google Scholar.

    Anne Gompel. Mary Ann Lumsden. Hassan Murad. Cite Citation. Permissions Icon Permissions. Open in new tab Download slide. Approach to menopause guideline. Numbers correspond to section of text addressing selected clinical issue. Table 1. This phase incorporates the perimenopause by extending for a longer variable period before and after the perimenopause. Open in new tab.

    Table 2. Table 3. TIA, transient ischemic attack. Table 4. Table 5. Table 6. Table 7. Table 8. Ensure absorption: if transdermal, consider serum estradiol determination. Atrophic endometrium in women more remote from menopause may respond to increased estrogen dose if otherwise appropriate. Changing to tibolone may be helpful in women who develop mastalgia on conventional MHT.

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    Transdermal ET is preferred. If oral estrogen is selected, monitor serum TG levels 2 wk after starting therapy. Abbreviation: TG, triglycerides. Table 9. Table Search ADS. A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. Oral vs. Menopausal hormonal therapy and mortality: a systematic review and meta-analysis.

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    Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, — Effects of hormone replacement therapy on endometrial histology in postmenopausal women. Comparative endometrial histology in postmenopausal women with sequential hormone replacement therapy of estradiol and, either chlormadinone acetate or micronized progesterone. Incidence of cancer among women using long versus monthly cycle hormonal replacement therapy, Finland — Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case control study.

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    Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52, women with breast cancer and , women without breast cancer. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.

    Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Obesity and insulin resistance in breast cancer—chemoprevention strategies with a focus on metformin. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin.

    Do the dose or route of administration of norethisterone acetate as a part of hormone therapy play a role in risk of breast cancer: national-wide case-control study from Finland. Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.

    Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. A commentary on a recent update of the ovarian cancer risk attributable to menopausal hormone therapy. Reproductive endocrinology: menopausal hormone therapy-ovarian cancer risk revisited. Conjugated equine estrogens and coronary heart disease: the Women's Health Initiative. Hormone therapy and risk of myocardial infarction: a national register study.

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    Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. Postmenopausal hormone use and cholecystectomy in a large prospective study.

    Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort. Hormone replacement therapy and symptomatic gallstones - a prospective population study in the EPIC-Norfolk cohort.

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    Evaluation of the performance of existing non-laboratory based cardiovascular risk assessment algorithms. Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the Women's Health Initiative trials of hormone therapy. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Coronary heart disease events in the Women's Health Initiative hormone trials: effect modification by metabolic syndrome: a nested case-control study within the Women's Health Initiative randomized clinical trials.

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    Catalog Record: Physiology : the basis of clinical practice | HathiTrust Digital Library

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    Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women. Serum estradiol-binding profiles in postmenopausal women undergoing three common estrogen replacement therapies: associations with sex hormone-binding globulin, estradiol, and estrone levels.

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    Psychoneuroendocrinology; the scientific basis of clinical practice - Semantic Scholar

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    Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Oral micronized progesterone for vasomotor symptoms—a placebo-controlled randomized trial in healthy postmenopausal women.

    The Endocrine Society re-issues position statement on bioidentical hormones. Press release. Published February 5, Conjugated estrogens combined with bazedoxifene: the first approved tissue selective estrogen complex therapy. Breast effects of bazedoxifene-conjugated estrogens: a randomized controlled trial. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Binding of adenine nucleotides and pyrophosphate by the purified coupling factor of photophosphorylation.

    Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: a comparison. Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study. Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women. A randomized study of the effects of tibolone and transdermal estrogen replacement therapy in postmenopausal women with uterine myomas.

    A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Discontinuing postmenopausal hormone therapy: an observational study of tapering versus quitting cold turkey: is there a difference in recurrence of menopausal symptoms?

    Tapering versus cold turkey: symptoms versus successful discontinuation of menopausal hormone therapy. How best is to discontinue postmenopausal hormone therapy: immediate or tapered? Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization.

    Increased need for thyroxine in women with hypothyroidism during estrogen therapy. Adiposity and reporting of vasomotor symptoms among midlife women: the study of women's health across the nation. Gains in body fat and vasomotor symptom reporting over the menopausal transition: the study of women's health across the nation. An intensive behavioral weight loss intervention and hot flushes in women. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial.

    Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative.