Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

Osteoporosis treatment and prevention for postmenopausal women: current and future therapeutic options.

Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle modification with nutritional counseling is recommended during menopausal transition. Bone density testing is recommended for women aged 65 years and older, younger postmenopausal women with risk factors, or to follow therapy. Bisphosphonates treat osteoporosis (prevent bone resorption). Raloxifene and hormone therapy prevent bone loss and fracture, with extraskeletal benefits. Denosumab treats osteoporosis, although bone effects reverse rapidly. Teriparatide (anabolic therapy) is considered for women at high risk of fracture. Bazedoxifene with conjugated estrogens, novel delivery of teriparatide, new parathyroid hormone proteins, anti-sclerostin antibodies, cathepsin K inhibitors, and stem cell therapies are in testing.

Advances in the treatment of menopausal symptoms.

Vasomotor symptoms and vaginal atrophy are both common menopausal symptoms. Hormone therapy is currently the only FDA-approved treatment for hot flashes. Current recommendations are to use the lowest dose of hormone therapy for the shortest period that will allow treatment goals to be met. Although the reanalysis of the WHI in 2007 by Roussow et al. provided evidence of coronary heart safety for users of hormone therapy under the age of 60 years and within 10 years of the onset of menopause, not all women desire or are candidates for hormone therapy. In this review we present an evidence-based discussion considering the effectiveness of hormonal and nonhormonal therapies for the relief of vasomotor symptoms and vaginal atrophy. Concern exists regarding systemic absorption of vaginal estrogen and possible adverse effects on the breast and uterus. Selective estrogen receptor modulators and estrogen agonists offer benefits through targeted estrogen agonist/antagonistic effects and are being evaluated with and without estrogen for symptomatic menopausal women. Centrally acting nonhormonal therapies that are effective for the relief of vasomotor symptoms include various antidepressants, gabapentin and clonidine. A limited number of clinical trials have been conducted with nonprescription remedies, including paced respiration, yoga, acupuncture, exercise, homeopathy and magnet therapy, and some, but not all of these, have been found to be more effective than placebo. Dietary herbal supplements, such as soy and black cohosh, have demonstrated mixed and inconclusive results in placebo-controlled trials. Potential therapies for vasomotor symptoms and vaginal atrophy require randomized, placebo-controlled trials of sufficient duration to establish efficacy and safety. Agents under investigation for vasomotor symptoms relief include neuroactive agents, such as gabapentin and desvenlafaxine; an estrogen receptor-beta-targeted herbal therapy, MF-101; and the selective estrogen receptor modulator, bazedoxifene, paired with estrogen.

MF-101, an estrogen receptor beta agonist for the treatment of vasomotor symptoms in peri- and postmenopausal women.

During peri- and postmenopausal stages, the majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, that interfere with sleep and reduce quality of life. Estrogen alone or in combination with a progestagen has been the standard therapy for such vasomotor symptoms; however, this therapeutic regimen is associated with severe side effects, such as breast cancer or cardiovascular events. To provide a better treatment option for menopausal women, Bionovo Inc is developing the estrogen receptor (ER)beta-selective agonist MF-101. Selective ER agonists can stimulate either ERalpha or ERbeta and induce tissue-specific estrogen-like effects, thus providing a safer alternative to conventional hormone therapy. MF-101 is derived from 22 herbs that are traditionally used in Chinese medicine for the treatment of menopausal symptoms. MF-101 did not promote the growth of breast cancer cells or stimulate uterine growth in preclinical studies and, in a phase II trial, was demonstrated to be safe and more effective in reducing the frequency and severity of hot flashes in postmenopausal women compared with placebo. To confirm the safety and efficacy of MF-101, larger phase III trials were planned for 2009. Although MF-101 appears to be a promising therapeutic, the herbal composition of the drug may be a disadvantage, because of the increased risk of causing allergic reactions in the general population. Studies with the MF-101-isolated active compounds liquiritigen and chalcone demonstrated selectivity for ERbeta, with no induction of proliferative events. If these isolates were demonstrated to be as effective and safe in clinical trials as preliminary data suggest regarding MF-101, these compounds could change the way clinicians treat menopause-associated symptoms.