Hot flushes

Estrogens and progestins are diminished in menopausal or ovarectomized women. In hormone replacement therapy (HRT), these hormones are substituted to alleviate hot flushes, mood changes, sleep disorders, and osteoporosis. 

Reduction in physcat symptoms of menopause hot flushes night sweats headaches heart palpitations dizziness vaginal atrophy, and tinnitus (ringing in the ears)... 

Hot flushes, hypertension, dizziness, paresthesia, insomnia, rash, constipation, nausea, diarrhea, nocturia, hematuria, peripheral edema, bone pain, dyspnea, general pain, back pain, asthenia, infection... 

Hot flushes, nausea, vomiting, vaginal bleeding, vaginal discharge, menstrual irregularities, skin rash... 

Hot flushes, skeletal pain, injection site pain, hypertension, headache, insomnia, dizziness, vomiting, diarrhea, impotence... 

SERMs Hot flushes, signs or symptoms of thromboembolic disease (e.g., pain, redness, or swelling in one extremity chest pain, and shortness of breath). 

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

Flutamide 750 mg/day Gynecomastia Hot flushes Gastrointestinal disturbances (diarrhea) Liver function test abnormalities Breast tenderness Methemoglobinemia... 

Compare and contrast the treatment options for management of hot flushes in ovarian cancer patients. 

Hot flushes, leg cramps, venous thromboembolism, peripheral edema, rare cataracts and gallbladder disease black box warning for fatal stroke... 

Raloxifene is well tolerated overall. Hot flushes occur more frequently in women recently finishing menopause or discontinuing estrogen therapy (ET). Endometrial bleeding occurs rarely. Raloxifene is contraindicated in women with an active or past history of venous thromboembolism. Therapy should be stopped if a patient anticipates extended immobility. 

Estrogens are FDA approved for prevention of osteoporosis, but they should only be used short-term in women who need ET for the management of menopausal symptoms such as hot flushes. The risks of long-term ET outweigh the potential bone benefits. 

Menopause is the permanent cessation of menses following the loss of ovarian follicular activity. Perimenopause is the period immediately prior to the menopause and the first year after menopause. Indications of postmenopausal hormone therapy include the short-term treatment of menopausal symptoms (i.e., hot flushes, night sweats, and urogenital atrophy). 

Vasomotor symptoms (e.g., hot flushes and night sweats) are common short-term symptoms of estrogen withdrawal, which usually disappear within 1 to 2 years but sometimes persist for 20 years. 

Current data suggest that phytoestrogens are no more effective than placebo for hot flushes or other symptoms of menopause. 

Most women with vasomotor symptoms need hormone treatment for less than 5 years. Without treatment, hot flushes usually disappear within 1 to 2 years. Hormone therapy can usually be tapered and stopped after about 2 or 3 years. 

Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

In cases of secondary amenorrhea, symptoms may include hot flushes, night sweats, fatigue, and mood changes. In primary amenorrhea, incomplete development of secondary sex characteristics may occur. 

The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. 

Aldrighi JM, Quail DC, Levy-Frebault J, Aguas F, Kosian K, Carrido L, et al. (2004) Predictors of hot flushes in postmenopausal women who receive raloxifene therapy. Am J Obstet Gynecol 191 1979-1988... 

Fig. 14.1. Incidence of hot flushes immediately before, diming, and after menopause stratified according to severity (redrawn from Oldenhave et al. 1993)...

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

MacLennan A, Lester S, Moore V (2004) Oral oestrogen replacement therapy versus placebo for hot flushes (Cochrane Review). In The Cochrane Library, Issue 1. Wiley, Chichester... 

As the first SNRI drug approved, venlafaxine has become one of the first-line choices for depression and anxiety disorder [45,46]. An active metabolite, desvenlafaxine (19), is also under clinical development for the treatment of major depressive disorders [47], Preclinical studies also indicate that 19 may be effective in relieving vasomotor symptoms associated with menopause (e.g., hot flushes and night sweats) [47,48]. Desvenlafaxine is reported to be in clinical development for the treatment of fibromyalgia and neuropathic pain, as well as vasomotor symptoms associated with menopause [68]. 

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