Pathological menopause: signs and tactics

The term "pathological menopause" was used to describe a severe course of menopause, when vasomotor and other symptoms are so severe that they disrupt sleep, work performance, and daily life. In modern clinical practice, "climacteric syndrome" or "moderate and severe vasomotor symptoms" are more commonly used, along with the genitourinary syndrome of menopause and psychoemotional manifestations. This shift in terminology emphasizes that we are not talking about a "disease of aging," but rather a spectrum of conditions that can be effectively treated. [1]

International classifications provide coding for both natural menopause and conditions associated with induced menopause. In the International Classification of Diseases, Tenth Revision, the group "Menopausal and Other Perimenopausal Disorders" has codes N95, including "menopausal and female climacteric conditions." The International Classification of Diseases, Eleventh Revision, provides separate entries for menopausal hot flashes, conditions associated with induced menopause, and other climacteric disorders. This helps standardize diagnosis and patient care. [2]

According to major guidelines, hot flashes and night sweats occur in most women during the transition to menopause, and in some, they persist for years. The median duration can be 7-10 years, with some experiencing longer. It is the duration and severity, rather than the occurrence of hot flashes themselves, that determine the clinical "pathology" of the condition and the need for drug therapy. [3]

The modern goal of treatment is not only to reduce the frequency and severity of hot flashes, but also to restore sleep, reduce daytime sleepiness and anxiety, and prevent bone loss and deterioration in quality of life. Both hormonal and proven non-hormonal methods exist for this purpose, including new targeted drugs. [4]

The Biology of Symptoms: Why Hot Flashes and Related Disorders Occur

A drop in estrogen levels disrupts the thermoregulatory circuits of the hypothalamus. Neurons containing kisspeptin, neurokinin B, and dynorphin play a key role. Their increased activity narrows the "comfort zone" of temperature sensitivity, causing normal fluctuations to be perceived as overheating and triggering a hot flash with vasodilation and sweating. Understanding this circuit has led to the development of drugs that block neurokinin receptors. [5]

Neural mechanisms are closely linked to lifestyle factors. Chronic stress, sleep deprivation, physical inactivity, and stimulants lower the threshold for episodes, while regular physical activity and normalized sleep improve resilience. Therefore, even in severe cases, non-drug measures enhance the effectiveness of medications and allow for a reduction in dosage. [6]

In addition to vasomotor symptoms, sleep disturbances, fatigue, depressed mood, and cognitive complaints are often observed. These manifestations are not always directly related to the frequency of hot flashes, so the assessment should be comprehensive, taking into account the impact on quality of life, not just the number of episodes. [7]

How often does this happen and how does the “pathological” variant differ from the normal one?

Vasomotor symptoms are reported by most women during peri- and postmenopause, but their severity and duration vary greatly. Longitudinal observations show that for many, severe symptoms persist for an average of 7-10 years, while for some, they persist for up to 14 years. Early onset, stress, and sleep disturbances are associated with a longer duration. This creates a "problematic" course that requires active treatment. [8]

Clinical trials often define "moderate-severe" hot flashes as at least seven episodes per day at baseline. This rule of thumb helps select patients for drug therapy and monitor their response. However, the decision is always individualized, as for some women, even less frequent episodes can seriously disrupt sleep and work. [9]

Validated questionnaires are used for objective assessment. The most well-known are the Greene scale and the specialized menopause quality of life questionnaire. These allow not only to record the severity of symptoms and their impact on daily life but also to monitor their progress during treatment. [10]

Diagnostics and initial assessment: what is really needed

In women over 45, the diagnosis of menopausal syndrome is based on clinical presentation and menstrual history. Routine hormonal testing to confirm menopause is not necessary for most women, as hormone levels fluctuate and can be misleading. It is more important to identify triggers, assess risk factors, and collaboratively determine treatment goals. [11]

Assessment tools help record baseline severity and then compare results. The Greene scale divides symptoms into psychological, somatic, and vasomotor domains. The Menopause Quality of Life Questionnaire covers vasomotor, psychological, physical, and sexual domains. The use of standardized scales facilitates shared decision-making and allows for more accurate assessment of the effectiveness of interventions. [12]

Particular attention is paid to bleeding after menopause. This is not a "normal" occurrence during menopause, but an indication for endometrial evaluation. A transvaginal ultrasound is often used for the initial evaluation. An endometrial thickness of 4 mm or less with bleeding is associated with a low risk of endometrial cancer, but if bleeding persists, further examination is required. [13]

When symptoms begin early, there are systemic manifestations, marked weight loss, persistent night sweats with fever, or an “atypical” picture, it is necessary to exclude other causes of hot flashes and sweating, including thyrotoxicosis, drug side effects, infectious and oncohematological processes. [14]

Differential diagnosis: not everything that is hot is menopause

Hot flashes and sweating may accompany thyrotoxicosis, adverse reactions to antidepressants and other medications, infectious diseases, and neuroendocrine tumors. The presence of fever, progressive diarrhea, severe arterial instability, episodes of palpitations with pallor and tremor, and significant weight loss are reasons to seek an alternative diagnosis. The rule is simple: if the symptoms are atypical for menopause or do not respond to standard therapy, the scope of examination is expanded. [15]

Treatment

Current guidelines recommend starting with an explanation of the nature of symptoms, addressing triggers and sleep hygiene, and, for moderate to severe vasomotor symptoms, discussing medication options. Hormonal therapy remains the most effective way to reduce the frequency and severity of hot flashes in appropriate patients. The decision is made individually, taking into account age, time since last menstruation, presence of a uterus, and risk factors. [16]

If hormonal therapy is contraindicated or undesirable, non-hormonal regimens with proven effectiveness are used: certain antidepressants, gabapentin for nighttime symptoms, and new targeted neuromodulatory therapies that act on neurokinin receptors. This step-by-step approach improves sleep and daytime well-being and helps achieve goals more quickly. [17]

New targeted drugs have expanded the choice. Fezolinetant, a neurokinin 3 receptor blocker, is approved for the treatment of hot flashes, but its use comes with warnings about rare but serious drug-induced liver injury, requiring liver function testing according to the approved regimen. In October 2025, the US Food and Drug Administration approved elizanetant, under the trade name Lincuet, which blocks the neurokinin 3 and neurokinin 1 receptors and also requires safety monitoring. [18]

Cognitive behavioral therapy for menopause and sleep hygiene reduce the subjective severity of hot flashes, help better manage episodes, reduce nighttime awakenings, and enhance the effectiveness of medications. Regular aerobic and strength training, weight management, cooling bedrooms, and avoiding personal triggers improve daily well-being. [19]

Table 1. Code according to ICD 10 and ICD 11

Classification	Code	Formulation
ICD 10	N95.1	Menopausal and female climacteric conditions
ICD 10	N95.3	Conditions associated with artificial menopause
ICD 11	GA30.00	Menopausal or female climacteric conditions
ICD 11	GA30.4	Menopausal hot flashes
ICD 11	GA30.3	Conditions associated with artificial menopause

Table 2. How to assess the severity of hot flashes in practice

Criterion	Lungs	Moderate	Heavy
Impact on activity	They don't interfere with business	They interfere partially	Significantly disrupt everyday life
Frequency according to diary	Rare episodes	Multiple episodes	Very frequent episodes
Threshold for drug therapy in clinical trials	There is no threshold	Individually	Often targeting ≥7 episodes per day at launch

Table 3. Validated monitoring tools

Tool	What does it measure?	Where is it useful?
Green scale	Psychological, somatic and vasomotor symptoms	Baseline assessment and dynamics during therapy
Menopause Quality of Life Questionnaire	Vasomotor, psychological, physical, sexual domains	Assessing the impact of symptoms on daily life
Tide Diaries	Daily frequency and severity of episodes	Monitoring the response to treatment

Table 4. Differential diagnosis of hot flashes and night sweats

Possible cause	Warning signs	First steps
Thyrotoxicosis	Weight loss, tremors, tachycardia	Thyroid hormones, examination
Infections	Fever, night sweats	Source search, basic analysis
Side effects of medications	Relationship with the start of therapy	Revision of the treatment regimen
Neuroendocrine tumors	Attacks with diarrhea and arterial lability	Targeted oncoassessment
Postmenopausal bleeding	Any "bloodbath"	Transvaginal ultrasound examination of the endometrium and further as indicated

Table 5. Choice of treatment strategy for severe cases

Clinical situation	What to offer first	Alternatives and additions
There are no contraindications to hormonal therapy.	Individually tailored hormonal therapy with regular reviews	Non-hormonal methods, cognitive behavioral therapy
Contraindications or reluctance to hormones	Non-hormonal drugs with proven effect	Cognitive behavioral therapy, trigger management, physical activity
Nighttime symptoms and sleep disturbances	Sleep hygiene, medications taken in the evening as prescribed	Cognitive behavioral therapy for insomnia
Insufficient response to the starting scheme	A new class of targeted agents based on indications	Combination of approaches under security control

Table 6. Non-hormonal drugs: guidelines and features

Class	Representatives and application guidelines	Comments by choice
Antidepressants with anti-tide activity	Paroxetine in a special low-dose form, other selective serotonin and norepinephrine reuptake inhibitors according to an individual regimen	Useful for anxiety and sleep disorders
Medications for nighttime symptoms	Gabapentin according to an individual regimen	Reduces hot flashes and improves sleep
Targeted neurokinin receptor antagonists	Fezolinetant, elinzanetant	Monitoring of liver function is required according to regulatory guidelines.

Table 7. Safety of new targeted agents

Preparation	Key risk	What to control
Fezolinetant	Rare but serious drug-induced liver injury	Liver function tests according to the approved regimen, immediate discontinuation if signs of hepatotoxicity occur
Elinzanetant	Monitoring liver safety according to the drug instructions	Baseline and follow-up liver function tests, consideration of interactions

When to see a doctor without delay

Any bleeding after menopause requires an endometrial assessment. An endometrial thickness of 4 mm during bleeding is considered reassuring, but if bleeding continues, the examination is further intensified, regardless of the thickness. Squeezing chest pain, shortness of breath, acute neurological symptoms, and high fever of unknown origin also require immediate medical attention. [20]

A practical 12-week plan for severe cases

During the first two weeks, baseline severity is recorded using the Greene Menopause Quality of Life Scale or the Menopause Quality of Life Questionnaire, triggers are addressed, sleep hygiene is initiated, and a medication approach is jointly selected. At 3-4 weeks, efficacy and tolerability are assessed, and the dosage or class of medication is adjusted if necessary. Between 5-8 weeks, psychological techniques are added and the regimen is consolidated. At 9-12 weeks, goals are redefined, and consideration is given to continuation, switching, or combining methods. [21]

Brief summary

"Pathological menopause," as it is currently understood, is a severe or prolonged course of climacteric syndrome, in which symptoms significantly impair quality of life. Diagnosis is made clinically, based on the severity and impact of symptoms, not solely on laboratory parameters. Hormonal therapy remains the most effective method for suitable patients, and for those who are not suitable, evidence-based non-hormonal treatments and new targeted drugs with mandatory safety monitoring are available. A structured plan, support from validated scales, and regular review of tactics can help restore sleep, productivity, and daily comfort. [22]