Hot flashes

Thought to be related to an estrogen related reduction in the body’s thermal neutral zone resulting in the release of heat if a woman’s core temperature rises even a little.

During menopause transition, estrogen levels initially increase, then decrease as the follicular pool is depleted, and gonadotropin levels increase in response.

Estrogen levels do not correlate with symptoms.

Severity in vasomotor vasomotor symptom begin before a consistently hypoestrogenic state exists.

Estrogen withdrawal causes hypertrophy of neurons in the hypothalamus coexpressing kisspeptin neurokinin B,  and dynorphin, which affect thermal regulation that control heat dissipation

Associated with signs of cutaneous vasodilation and subsequent drop in core body temperature.

Hot flashes and night sweats, also called vasomotor symptoms are common symptoms associated with hormone depletion , occurring in approximately 75% of women during the menopause transition.

Risk for hot flashes include early or surgical menopause, black race, Hispanic ethnic group, high body mass index, sedentary lifestyle, smoking, stress, anxiety, depression, posttraumatic stress disorder, partner violence, sexual assault, and the use of selective estrogen receptor modulators or aromatase inhibitors.

Vasomotor symptoms result in diminished quality of life and affect work satisfaction, productivity, mood, and sleep

Can last for less than one minute or as long as 10-20 minutes.

May occur infrequently or more than 20 times daily.

Vasomotor symptoms persist for 7 to 10 years in most individuals and even longer in at least 10%.

On average people experience 4 to 5 vasomotor symptoms daily, but some experience as many is 20.

Vasomotor symptoms are most prevalent during the year of the final menstrual period, but often begin in menopause transition

Defined as a sudden sensation of intense warmth that often begins in the chest area, may rise to the neck and face, it may be accompanied by red blotches on the skin, profuse sweating, palpitations, anxiety, and embarrassment.

Hot flashes are described as experiences that last as long as 4 to 6 minutes.

They are associated with intense flushing, a sensation of heat, and sweating; and occur as often as 12 to 15 times a day.

Women may experience disturbed sleep because they are awakened once or twice a night by hot flashes.

Can be a major issue for many women that sometimes lasts years.

Hot flashes persist a median of 7.4 years, and that duration varies according to race or ethnic group-five years among Asian women, seven years among white women, nine years among Hispanic women, and 10 years among black women (Avis NÉ).

Cause of vasomotor symptoms not fully understood.

Vasomotor symptoms could be related to oxidative stress and adverse cardiovascular disease risk profile.
Severe menopausal symptoms have been associated with hypertension, elevated total cholesterol levels, increase cardiovascular events compared with female patients with no or few symptoms.
It is suggested that sub clinical atherosclerosis is more prevalent in female patients with severe vasomotor symptoms.
Menopausal vasomotor symptoms are associated with increased sympathetic and decreased parasympathetic function, which could enhance the risk of cardiovascular events.

Vasomotor symptoms are exacerbated by increasing insulin resistance and inflammatory factors derived from visceral adipose tissue, which she has increased activity after menopause.

Drop in estrogen and an increase in follicle stimulating partly responsible.

Changes in woman’s regulation of core temperature and genetic variations related to metabolism of sex hormones associated with vasomotor symptoms.

Thought to be a result of dysfunction in the central thermoregulation set point in the hypothalamic center as a result of decreased estrogens or decreased gonadal steroid levels.

It has been suggested that with the withdrawal of estrogen levels an imbalance in neurotransmitter levels occur.

Symptoms can range from mild feeling of warmth to excessive sweating, heart palpitations, irritability, panic and night sweats.

Duration of symptoms can vary from seconds to several minutes and from mild to intolerable degrees.

Occur in 30-80% of menopausal women.

Women with hot flashes undergoing treatments that cause early menopause may have hot flashes that are more severe and last longer.

Women with hot flashes do not have higher body temperatures than women who do not.

Women with hot flashes are more likely to start sweating or chilling due to the narrowed thermal neutral zone, so that slight rises or decreases in body temperature cause the symptoms.

Massachusetts Women’s Health Study revealed 85% of postmenopausal women have hot flashes over a period of 3-5 years.

10% of women still have hot flashes at age 70 years.

Because of potential adverse effects of hormone therapy, (increased risk of venous, thromboembolism, stroke, and breast cancer with combined estrogen plus progesterone therapy) vasomotor symptoms should only be treated if they are bothersome.

Estrogen therapy effective more than 85% of the time.

Systemic estrogen by oral, vaginal, or trans dermal administration is the most effective treatment for menopausal vasomotor symptoms, reducing hot flashes by 50-100% within four weeks.

Hot flashes occur in as many as 75% of menopausal women in the US and while symptoms are not life-threatening, they can greatly affect the quality of life by disrupting daily activities and impairing sleep.

Average duration of vasomotor symptoms is greater than seven years, up to one third of women experience moderate-severe symptoms for 10 or more years.

For decades estrogen monotherapy has been recommended for women who have had a hysterectomy and estrogen plus progestin combination therapy have been prescribed for women who have not.

The lowest effective dose of hormone therapy for the shortestmduration, consistent with the patient’s need and periodic reevaluation are needed for continued hormone therapy to control symptoms.

Women with a uterus, in situ should be prescribed progestational agents to reduce the risk of endometrial hyperplasia and endometrial cancer.

Ambient temperature may affect the frequency and severity of of hot flashes.

Common side effect of tamoxifen, raloxifene and aromatase inhibitors.

Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMS) and interfere with estrogen receptor modulators causing thermoregulatory dysfunction.

Tamoxifen associated with hot flashes in up to 80% of individuals and 30% experience severe symptoms.

Soy and herbal remedies effective in up to 50% of the time in randomized controlled studies.

Alternatives to hormone therapy for vasomotor symptoms include serotonin, norepinephrine, reuptake inhibitors, selective serotonin, reuptake inhibitors, and gabapentin.

Venlafaxine decreases hot flashes by 55% at the 75 mg/day dose.

Desvenlaxafine at 100mg/day associated with greater than 50% redution in hot flashes by 12 weeks.

Paroxetine is approved for the treatment of moderate to severe vasomotor symptoms associated with menopause.

Paroxetine use results in a substantial decrease in hot flashes in women compared to placebo.

Paroxetine use in men on ablative androgen therapy have a reduction in hot flashes.

Paroxetine recommended starting dose is 10 mg a day, and because it is a potent inhibitor of CYP2D6 and should not be used with tamoxifen.

Fluoxetine It is less successful than other antidepressants for reducing hot flashes.

Experienced by 75% of men receiving androgen ablation therapy.

Low dose venlafaxine use results in a reduction of hot flashes in women with breast cancer and men on androgen ablative therapy.

Fezolinetant is a NK3R antagonist that reduces vasomotor symptoms.

NKB antagonists used for the treatment of vasomotor symptoms are comparable to menopausal hormone therapy.

Most agents that diminish hot flashes in women do so in men as well.

Hot flashes affect  up to 75% of patients undergoing medical or surgical androgen deprivation therapy in prostate cancer  (Schow DA et al).

Hot flashes in men treated for prostate cancer with hormonal therapy are often accompanied by anxiety, irritability, and feeling of being out of control (Charig CR et al).

Clonidine has some effectiveness in treating hot flashes in women but not in men.

Estrogen  and progesterone analogues have treatment efficacy in men  reduce hot flashes in men by approximately 75%, compared to 25% reduction with placebo (Loprinzi CL et al, Atala A et al).

In a randomized, double-blind, placebo-controlled trial of 60 postmenopausal women aged 35 to 60, were randomly assigned to recieve either gabapentin titrated to 2400 mg/d, traditional therapy with 0.625 mg/d of conjugated estrogens or placebo for 12 weeks: estrogen and gabapentin markedly outperformed placebo, and by 12 weeks, the results with gabapentin and estrogen were nearly indistinguishable.

Gabapentin  600-900 mg per day is better for treating hot flashes in men with prostate cancer than 300 mg.

Oxybutynin significantly improves hot flash frequency and severity and is associated with a positive impact in several quality of life metrics.

On average vasomotor symptoms are experienced for about 7 years.

Keeping room temperature cool, keeping air moving with fans, dressing in layers, and wearing open fabrics may have therapeutic benefits.

Avoiding alcohol, tobacco, and caffeine may be of benefit.

More common in African-American women and less common in Asian women.

More common in obese women.

Women who are overweight/obese tend to have more severe or more frequent hot flashes during menopause transition than normal weight counterparts.

Weight loss is beneficial.

Weight loss is associated with Improvement in vasomotor symptoms.

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