Symptoms of menopause

Vasomotor symptoms
Vasomotor symptoms are associated with decreased sleep quality, irritability, difficulty concentrating, reduced quality of life¹, and poorer health status. According to the Study of Women’s Health Across the Nation, frequent vasomotor symptoms persisted on average for 7.4 years² and appear to be linked to cardiovascular, bone, and cognitive risks³.

Hot flashes: A sudden sensation of intense heat experienced primarily in the upper body, such as the face, neck, and chest.

Key features of hot flashes:

1. Sudden onset: It begins as a rapidly spreading sensation of heat.
2. Duration: They can last from a few seconds to several minutes.
3. Perspiration: It is common for it to be accompanied by sweating, especially in the upper body.
4. After-cooling: Some women feel chills once the hot flash ends.
5. Frequency and severity: They vary between women, from occasional episodes to multiple a day, with mild to debilitating intensity.

Hot flashes are one of the most common symptoms of perimenopause and menopause, affecting approximately 75-80% of women during this stage. While they usually decrease over time, in some women they can persist for several years.

In more detail, how is body temperature regulated?

Body temperature is controlled in several ways, one of them is through KNDy neurons, which send signals to the temperature regulating center of the brain through Neurokinin B, which, in turn, also has a receptor in the KNDy neurons.
Estrogens inhibit KNDy neurons.
Neurokinin B increases body temperature, and estrogens lower it.

The temperature regulating center of the brain also receives information from the environment.

During menopause, the level of estrogen decreases, which means that the inhibition of these neurons is lost, which also increase in size. This causes the temperature regulating center to perceive greater stimulation and creates the sensation of increased temperature without the body temperature actually increasing.

The brain sends a signal to the skin, which feels hot and sweaty, as a mechanism of loss of temperature, since the temperature regulating center of the brain interprets that the body temperature is high and looks for ways to balance it by losing heat.

Since body temperature was not actually elevated, the body actually loses heat as a result of this process, which is why many women experience shivering and shaking after a hot flash.

Compared with placebo, estrogen therapy (ET) alone or combined with progestogen (EPT) was found to reduce weekly symptom frequency by 75% (95% CI, 64.3-82.3) and significantly decrease symptom severity (odds ratio [OR], 0.13; 95% CI, 0.07-0.23)⁴.

Sleep disturbances

Sleep disturbances are common after menopause and begin during perimenopause⁴. Sleep disruptions are strongly associated with vasomotor symptoms (VMS) and a decrease in quality of life. Poor sleep quality has been linked to mood fluctuations, memory problems, metabolic syndrome, obesity, and other cardiovascular risk factors. Short (or very long) sleep duration, poor sleep quality, and insomnia have been associated with an increased risk of cardiovascular disease (CVD).
Hormonal therapy in the form of low-dose estrogen or progestogen may improve chronic insomnia in menopausal women, with 14 of 23 reviewed studies showing positive results⁴. There is some evidence that transdermal estrogen (ET) may benefit sleep in perimenopausal women, independent of vasomotor symptoms.

Genitourinary symptoms

Genitourinary syndrome of menopause (GSM) includes the signs and symptoms associated with menopause-related estrogen deficiency, affecting the labia, vagina, urethra, and bladder, and includes vulvovaginal vaginal atrophy⁴ (VVA). Symptoms may include genital dryness, burning, and irritation; sexual symptoms such as decreased lubrication and pain during sexual activity; and urinary symptoms such as urgency, dysuria, and recurrent urinary tract infections (UTIs).

Estrogen therapy, specifically vaginal estrogen therapy (vaginal ET), is an effective treatment for GSM, with no evidence to suggest differences in safety or efficacy between various vaginal ET preparations.

Use of vaginal estrogens showed a decrease in the incidence of incontinence and overactive bladder, with one to two fewer micturitions in a 24-hour period, in addition to a reduction in urinary frequency and urgency⁴. Randomized controlled trials (RCTs) have shown a reduction in the risk of recurrent urinary tract infections (UTIs) with the use of vaginal estrogens, but not with oral estrogens.

Sexual function

Sexual interest, arousal, and orgasmic response are distinct aspects of human sexual function and can be influenced by a variety of factors, including biological, psychological, and social factors. While these aspects can be affected by hormonal changes (such as those that occur during menopause), they are not solely dependent on menopause or the treatment of its symptoms

Hair and skin changes

Changes in hair density and female-pattern hair loss worsen after menopause, but research is insufficient regarding the role of hormone therapy in mitigating these changes4.
Estrogen therapy may benefit wound healing by modifying inflammation, stimulating granulation tissue formation, and accelerating reepithelialization. Estrogen therapy increased epidermal and dermal thickness, increased collagen and elastin content, and improved skin hydration, with fewer wrinkles5.

Osteoporosis

Menopause is associated with increased bone resorption, and estrogen therapy (ET) decreases bone resorption⁷. Hormone therapy prevents bone loss in healthy postmenopausal women, with dose-related effects on bone density.

However, MHT is not approved for treating osteoporosis, although it is approved for preventing osteoporosis⁷. It reduces the risk of fractures in healthy postmenopausal women.

Joint pain

The direct binding of estrogen to estrogen receptors acts on joint tissues, protecting their biomechanical structure and function and maintaining overall joint health⁸. However, the exact effect of estrogen on osteoarthritis remains controversial.

A clear association between hormone therapy use and osteoarthritis has not been observed⁸.

Women in the WHI and other studies experienced less joint pain or stiffness with hormone therapy compared to placebo⁴.

Better understanding of the potential effect of estrogen on joint health is needed.

Weight and body composition

The menopausal transition is associated with an increase in body fat and a decrease in lean body mass, resulting in an increase in the fat-to-lean mass ratio and a decrease in basal metabolic rate. After adjusting for body size and ethnicity, the average weight gain during midlife and the menopausal transition is 0.68 kg per year⁹. Central fat distribution (gynoid to android pattern) also occurs after menopause, after adjusting for aging, total body fat, and physical activity level. Approximately 2 years after the last menstrual period, weight changes plateau.

Women who used hormone therapy had no observable differences in weight gain or body fat trajectory compared to those who did not take hormones9, although the numbers are relatively small.

MHT – cognition

The relationship of MHT to memory and cognitive abilities is unclear, with studies showing conflicting results.

There are two hypotheses¹⁰ to explain this apparent contradiction between benefit and detriment: the critical window or timing hypothesis and the healthy cell bias hypothesis. Both provide a framework for understanding the scientific literature on hormone therapy and cognition, but neither has been definitively supported in randomized controlled trials (RCTs) in postmenopausal women. The critical window or timing hypothesis holds that estrogen may confer cognitive benefits if given early in the menopausal transition, but its use later is neutral or detrimental. The healthy cell bias hypothesis posits that estrogen offers cognitive benefits when the neural substrate is “healthy” and not diseased, for example, in a woman without type 2 diabetes.

The NAMS panel concluded that in the absence of more definitive findings, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia⁴.

MHT – depressive symptoms

There are different studies on depressive symptoms during menopause, and it is not clear whether these disorders are more common during perimenopause compared to premenopause¹¹. Women with a previous diagnosis of depression may have worsening symptoms during menopause.

There is some evidence that estrogen therapy (ET) has antidepressant effects of similar magnitude to those seen with antidepressant agents when administered to depressed perimenopausal women¹¹. There is some evidence that ET improves mood and well-being in non-depressed perimenopausal women.

Estrogen therapy is ineffective as a treatment for depressive disorders in postmenopausal women¹¹.

This evidence suggests a possible window of opportunity for the effective use of ET in the management of depressive disorders during perimenopause, although the evidence is insufficient to recommend estrogen-based therapies to prevent depression in asymptomatic perimenopausal or postmenopausal women, and the risks and benefits must be weighed.

Estrogens are not approved by government agencies to treat mood disorders⁴.

MHT – cardiovascular events – all-cause mortality

The effect of MHT is different according to age group and time since menopause onset.

Initiation of hormone therapy in recently postmenopausal women reduced or had no effect on the progression of subclinical atherosclerosis and coronary artery calcification in randomized controlled trials⁴.

Women who initiate hormone therapy after age 60 years or more than 10 to 20 years after the onset of menopause have higher absolute risks of CHD, VTE, and stroke compared with women who initiate hormone therapy at the onset of menopause⁴.

The conclusion⁴ is that in healthy, symptomatic women younger than age 60 years or within 10 years after the onset of menopause, the favorable effects of hormone therapy on coronary heart disease (CHD) and all-cause mortality should be weighed against possible rare increases in the risks of breast cancer, venous thromboembolism (VTE), and stroke. Despite this favourable effect on this profile of women, hormone therapy is not approved by governments for primary or secondary cardioprotection.

HMT – breast cancer

The risk of breast cancer associated with the use of hormone therapy is low, with estimates indicating a rare, infrequent occurrence⁴ (less than one additional case per 1,000 women per year of hormone therapy use or three additional cases per 1,000 women when used for 5 years with CEE plus MPA).

The benefits and risks of HMT should be raised in the consultation.

Women should be advised about the risk of breast cancer associated with hormone therapy, putting the data into perspective, with a risk similar to that of modifiable risk factors such as the consumption of two alcoholic drinks per day, obesity and low physical activity^12,13. That is, this increased risk of breast cancer associated with HMT is below the risk caused by other factors such as alcohol, obesity or a sedentary lifestyle.

The effect of hormone therapy on breast cancer risk may depend on the type of hormone therapy, duration of use, regimen, prior exposure, and individual characteristics^12,13. Different hormone therapy regimens may be associated with increased breast density, which may make mammographic interpretation more difficult, leading to more mammograms or breast biopsies and a possible delay in breast cancer diagnosis¹⁴.

HMT – quality of life

Quality of life is defined as a general assessment of a person’s life in relation to their goals and expectations. Quality of life can apply to a person’s mental and physical health. Menopausal symptoms are associated with poorer health-related quality of life and menopause-specific quality of life. Systemic hormone therapy may improve menopause-specific quality of life in women experiencing menopausal symptoms⁶

Conclusion:

MHT is another tool for treating symptoms associated with menopause that should be considered as a valid alternative for many, but not all, women.

The decision should be individualized, taking into account the personal factors of each patient, who is unique. Despite the side effects, the misunderstood fear of hormones should not cause many women to lose the opportunity to access a treatment with many benefits.

Patients with a personal or family history of hormone-dependent cancer should not take hormone treatment. Obese patients or those with other risk factors, who are older, or who have been since menopause for a longer period, should not consider it either.

However, patients in perimenopause or who have recently entered menopause, without associated risk factors, and who take the treatment for less than 5 years, could have benefits that outweigh the risks of taking the medication.

Bibliography

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