Postmenopausal Hyperhidrosis and Vasomotor Symptoms in Menopause Should be Treated Differently – A Narrative Review

Postmenopausal hyperhidrosis (PMH) is an important differential diagnosis to vasomotor symptoms (VMS) in menopause. The objective is to describe the differences in clinical presentation and treatment of the two conditions. Patients suffering from PMH represent a unique cohort of patients with primary hyperhidrosis and should therefore not be treated in the same way as those displaying VMS during menopause. Postmenopausal hyperhidrosis is a neglected differential diagnosis to the common VMS in menopause. The two diagnoses have similarities but also distinct differences in presentation. However, the treatments of the diagnoses differ substantially. This review explains the differences in clinical presentation and treatments and suggests botulinum toxin type B in the treatment of vasomotor symptoms due to anti-oestrogen therapy. Swartling C, Naver H, Cabreus P. Postmenopausal Hyperhidrosis and Vasomotor Symptoms in Menopause Should be Treated Differently – A Narrative Review. Arch Obstet Gynecol. 2021; 2(3): 57-63. Arch Obstet Gynecol. 2021 Volume 2, Issue 3 58 These are controlled by nuclei in the preoptic area of the hypothalamus. The eccrine sweat glands are innervated by sympathetic fibres with acetylcholine as transmitters. Important co-transmitters in the postganglionic sweat fibres are VIP (vasoactive peptide) and CGRP (calcitonin gene-related peptide) which with vasodilation and increased vasopermeability provide extravasation of plasma to the sweat glands, which via the sweat exits later becomes a hypotonic salt-containing sweat. While sweat eliminates heat by way of evaporation, where one millilitre of evaporated sweat corresponds to 0.58 kcal energy reduction, redirected blood flow to the skin does so by radiating excess heat to a cooler (< 37°Celsius) environment [3]. Thermoregulatory vasodilation is regulated via reduced stimulation of adrenergic receptors, but the neuropeptides in the nerve endings of the sweat glands can also play a role [1]. Primary Hyperhidrosis Primary hyperhidrosis is an inherited disability in 4.8% of the population and produces a major negative impact on quality of life [4]. The condition is characterised by low thresholds for stimuli such as stress (arousal), heat and exertion, in the sweat-regulating systems of the central nervous system (CNS), which in addition to the hypothalamus also include the limbic system and frontal cortex [5]. Arousal leads to a pathologically increased sympathetic outflow to the sweat glands in patients with hyperhidrosis compared to a normohidrotic control group [6]. Sweat in the palms of hand and soles of the feet, as well as in the paws of many mammals, is crucial for the grip function during “fight and flight”, which explains why nuclei in the limbic system are sweat-regulating and that stress can be a deteriorating factor in patients with mainly thermoregulatory hyperhidrosis which is found on large body surfaces, such as the head and torso. Age of onset varies: hands-feet often debut in childhood, armpits-groin/buttocks/genitalia during adolescence, and head-torso tend to debut later in life. Patients with hyperhidrosis usually sweat abnormally much from more areas of the body, and the process is long-lasting and, for many, lifelong [5]. The diagnostic criteria for primary focal hyperhidrosis were established at an international meeting of experts in New York and were defined as bilateral symmetrical excessive sweating for at least 6 months, and at least two of the following bi-criteria: troublesome sweating at least twice a week, heredity, anhidrosis during sleep, reduced quality of life and onset before the age of 25 years [7]. However, the New York meeting did not provide guidelines for thermoregulatory hyperhidrosis, often referred to as general hyperhidrosis, including the head and torso. Of the thousands of patients with thermoregulatory hyperhidrosis that we have treated, the age of onset is often later than 25 years and nocturnal sweating is not uncommon, i.e., contrary to the diagnostic bi-criteria for primary focal hyperhidrosis of the hands, feet and armpits. Thermoregulatory hyperhidrosis has many characteristics similar to those of VMS during menopause (Figure 1). Secondary hyperhidrosis accounts for a small proportion of all people with hyperhidrosis and must be excluded. The underlying causes can be medication, denervation, endocrine disorders, cancer or infections. It is usually easy, using few anamnestic data, to distinguish primary hyperhidrosis from secondary ditto, but in certain cases further investigation is required (Table 1) [5]. Figure 1: Postmenopausal hyperhidrosis (PMH) and Vasomotor symptoms in menopause (VMS) have great similarities with probable overlap. Patients with primary hyperhidrosis may be impaired by declining oestrogen levels, and during a period in the course of the illness experience a partial improvement from oestrogen substitution. At the same time, patients with therapy-resistant VMS may instead exhibit strong symptoms of PMH where botulinum toxin type B should be used before oestrogen supplementation. Swartling C, Naver H, Cabreus P. Postmenopausal Hyperhidrosis and Vasomotor Symptoms in Menopause Should be Treated Differently – A Narrative Review. Arch Obstet Gynecol. 2021; 2(3): 57-63. Arch Obstet Gynecol. 2021 Volume 2, Issue 3 59 Postmenopausal Hyperhidrosis Postmenopausal hyperhidrosis is a misleading name for primary thermoregulatory hyperhidrosis in postmenopausal women. The name suggests that menopause and declining oestrogen levels have something to do with the diagnosis. Ten percent of all women over the age of 70 years suffer from bothersome sweating, which probably does not only have to do with falling oestrogen levels [8]. In addition, the onset of hyperhidrosis can occur long before or after the onset of menopause. Our experience is that women sense when menopause stops and hyperhidrosis continues: the hot flashes disappear and the sweating becomes situation dependent (stress/ heat/effort). The majority suffering from PMH who seek help at a Sweat Clinic medicate or have medicated with oestrogen despite the effect having diminished or completely disappeared. Many women express “that they understand that their pronounced sweating has nothing to do with menopause” but they continue with oestrogen replacement. This paradox is difficult to comprehend, but patients can sometimes express “that maybe it would be even worse if I stop”. Postmenopausal hyperhidrosis lacks the symptoms of hot flashes and is not helped by oestrogen substitution [9]. Postmenopausal hyperhidrosis often assails the headtorso region, but may also include other body areas. In a minor study, a double onset was noted with hyperhidrosis in adolescence from e.g., the armpits, followed by a troublefree interval and then pronounced sweating starting usually between 40 and 70 years of age [10]. Patients with PMH are often aware that it does not really have anything to do with menopause, and that pronounced sweating is often present in the family. Postmenopausal hyperhidrosis is situation dependent (heat/effort/stress) and lacks hot flashes as in VMS. Nocturnal sweats are common in both conditions. An important dividing line between the diagnoses is the response to oestrogen substitution, where PMH does not respond to treatment, unless the patient has it in combination with VMS (Table 2). Table 1: Anamnestic data distinguishing between primary and secondary hyperhidrosis. Primary hyperhidrosis Secondary hyperhidrosis