Hot flashes: epidemiology and physiology.

PART II. CURRENT RESEARCH-OVERVIEW AND UPDATE (continued)

Hot Flashes: Epidemiology and Physiologyu FRED1 KRONENBERG Department of Rehabilitation Medicine Columbia University College of Physicians & Surgeons New York, New York 10032

INTRODUCTION The hot flash is a common phenomenon of the menopausal period. For some women this means nothing more than an occasional, transient sensation of warmth; however, others experience hourly waves of heat, drenching sweats, and an increased heart rate. In addition, sleep may be disrupted several times a night, resulting in fatigue and irritability. Frequent hot flashes may be disabling, with attendant social, psychological and economic consequences, as reflected in the following illustrative comments made to me by women with hot flashes:

“I turned down a proposal for marriage. He lives in Alabama. If it had been Alaska, I would have said yes.” “I’m a pianist. When I’m playing and I have a hot flash, my fingers slip on the keys.” “My husband now sleeps in the living room, but at least I have my hot flashes to keep me warm.” “It’s very embarrassing when I’m showing a 2 million dollar apartment, and all of a sudden my face turns red, I break out in a sweat, and the client wonders what I’m hiding.” For years, women were told that hot flashes were “all in their heads.” More recently, hot flashes have become increasingly recognized as a biological phenomenon having a great impact on many women. Physicians typically view hot flashes as an acute problem that abates within months, or at most within a few years.’.* While this may be the case for most women, others must endure hot flashes for 10, 20, or sometimes more than 30 years. For these women hot flashes are not merely unpleasant episodes, but persistent and disruptive problems. Hot flashes are one of the chief menopausal complaints for which women in Western societies seek medical treatment. Yet, there are few options to help them

a This paper was partially supported by the Florence and Herbert Irving Endowment, the Vidda Foundation, and NIH GCRC Grant 5MOI RR00645 to Columbia University.

52

KRONENBERG: HOT FLASHES

53

cope with hot flashes. Estrogen is the most effective drug treatment for hot flashes, and, significantly ameliorates hot flashes for most women. But there are many women for whom it is contraindicated, or who choose not to risk its potential side effects. A search for other medications that would be safe and effective has yielded few treatment alternatives, and none approaches the effectiveness of estrogen. Little effort has been devoted to exploring possible nonpharmacologic remedies or nonmedical coping strategies. The numbers of women in their menopausal years is increasing. By the year 2000, it is estimated that there will be 719 million women in the world over the age of 45 (US.Bureau of the Census). In the U.S. today, one-third of all women are over 50 years old. If we take the estimates that about 75% of women will experience hot flashes, and that 15% are severely affected, then in the U.S. alone, 4-5 million women are markedly affected by their hot flashes. Despite the large numbers of women affected by hot flashes, there is insufficient information about the natural course of hot flashes, such as the average age at which hot flashes begin, factors that influence the age at hot flash onset, and specific triggers of hot flashes. We do not know why hot flashes last only a few months in some women, while in others they persist for years or never occur at all. In surveys of menopausal symptoms, hot flashes are often a single item on a list of possible complaints. Rarely are detailed questions asked about hot flashes, or about factors that may influence hot flash occurrence. We still do not understand fully the physiology of hot flashes, the mechanism by which a decline in estrogen level leads to hot flashes, or precisely how estrogen or any other therapy works to alleviate them. Women possess a wealth of seemingly individual, but actually common, subjective experiences of hot flashes, that may provide clues to causes of or remedies for hot flashes. This paper summarizes current knowledge about the epidemiology and biology of hot flashes and presents partial results of an exploratory survey which examined characteristics of hot flashes in 501 American women. Proposed neuroendocrine mechanisms of hot flashes have been covered in detail in several

TERMINOLOGY Hot flashes are defined subjectively as recurrent, transient periods of flushing, sweating, and a sensation of heat, often accompanied by palpitations and a feeling of anxiety, and sometimes followed by chills. “Hot flash,” “hot flush,” “night sweat,” and “vasomotor symptoms” are terms commonly used to describe the same phenomenon. Some make a distinction between the flush and the flush-the blushing and sensation of heat as separate from the sweating. Others consider night sweats to be different from hot flashes, but there is no evidence that the physiology of nocturnal hot flashes differs from that of daytime hot flashes. Although there are characteristic features of the hot flash, the magnitude and duration of any of these components (objective and subjective) can vary both within and between individuals. Thus, some individuals may sweat profusely during hot flashes, while others may sweat little or not at all. In 1882, Dr. E. J. Tilt, in a discussion of his search for an appropriate term for this phenomenon, explained his use of the word flush as “short and expressive,” while admitting that “ . . . ‘hot blooms’ . . . . faithfully indicates what really occurs . . . .”* The term “hot flash” is used here because it expresses the sudden and transient nature of the sensation of heat, flushing, and sweating.

54

ANNALS NEW YORK ACADEMY OF SCIENCES

EPIDEMIOLOGY Who Gets Hot Flashes Hot flashes are primarily a phenomenon of women who are in the transition to, or have become menopausal, either naturally, or due to some external intervention. Some premenopausal women describe having hot flashes, as do some women during pregnancy or immediately postpartum. Hot flashes can occur in both men and women after acute gonadal steroid withdrawal, such as ovariectomy in young women9 or orchiectomy in men,I0; in men or women who are hypogonadal,11J2;or in those who take gonadotropin-releasing hormone (GnRH) agonists, antagonists or other anti-gonadal agents which cause estrogen (in women) or testosterone (in men) levels to fall.133’4

Prevalence of Hot Flashes Information on the prevalence of hot flashes is based largely on studies of menopausal symptoms primarily among women between 40-60 years old, conducted in Western countries including Great Britain, the Netherlands, Scotland, Sweden, Canada and the United States. Hot flash prevalence for postmenopausal In the few studies in which the data women ranges from 24-93% (TABLEl).15-26 were analyzed by age group or number of years post menopausal, the prevalence of hot flashes is highest in the first 0-2 years post menopause, lessening with increased years post menopause. 16,20,22,27 In perimenopausal women, reports of hot flash prevalence vary from 28-65%, and in premenopausal women from 663%. 16,18-22,28 Women with surgically induced menopause tend to have a higher prevalence of hot flashes, at least for the first year post ovariectomy, than do naturally menopausal women (TABLE2).9,23,29,30 Discrepancies in prevalences of hot flashes reported in epidemiologic surveys probably reflect inconsistencies in research methodologies. Many of the salient issues have been identified by Goodman3* and Kaufert and colleague^.^^ One problem of inconsistency is the lack of uniformity in the definitions of pre-, periand postmenopausal phases so the age ranges and endocrine status of the women in these groups may differ among studies. Inconsistencies in hot flash terminology (hot flash, hot flush, flushing, sweating, night sweat, vasomotor symptom) may result in several hot flash terms being listed as distinct items on the same symptom list. In addition, most surveys have asked about current complaints; only a few have inquired about previous history of hot f l a s h e ~ . ~The ~ J groups ~ , ~ ~ studied are not always comparable: They may be patients seeking treatment, or well-woman general population samples. They may differ in mean age, age range, or number of years pre-, peri- or post menopause. Climate or season when the inquiry is made may also influence the outcome, since, for example, women have reported hot flashes to be “worse” when the weather is hot and humid. Finally, modes of survey administration (personal interview, postal questionnaire) differ and may influence responses. Thus, these methodologic differences make it difficult to compare results, even in studies of cultures that have many similar assumptions and attitudes towards menopause. A11 cultures do not share the same assumptions about menopause. This adds another level of complexity to interpretation of the roles played by biology and environment, both physical and sociocultural, in shaping the symptom profiles of different groups of women. Anthropologists and other social scientists have con-

m

Sweden General (Goteborg) population ( 1462) (7-12% artificial menopause)

1971 Rybo Westerberg

Netherlands We)

General population (2956)

1969 Jaszmann van Lith Zaat

Pre (999) Peri (804) 1-2 yr Post (141) 2-4 yr Post (213) 4-5 yr Post (99) 5-10 yr Post (677) Pre Post

Pre = normal menses 1 yr prior Meno = change in menstrual pattern in past year Post = no menses 2 1 yr

Pre = normal menstrual cycles Post-not defined

Pre (50) Pre/post (60) Post (40) Post (60)

Evaluated by subject

U.S.A. (Chicago)

1965 Neugarten Kraines

Post (61)

Age menses stopped

U.S.A. (Mississippi)

Hospital patients (80) Volunteers (460)

1964 Newton Odom

>5 yr Post (1197)

Age menses stopped

Investigator Definitions of Menopausal Statusb

England & Scotland

Location

Volunteers (1 197)

Author

Study Group" (Total N )

Menopausal Statusb (number of subjects by menopausal status)

38 46 50 54 60

45 48 53 54 55 58

30-44 45-54 45-54 55-64

54.6

29-91

Age Group (range or mean)

Survey Studies That Include Hot Flash Prevalence Data for Pre-, Peri-, and Naturally Postmenopausal Women

1933 Medical Women's Federation

Year

TABLE 1.

10 65 72 65 30

17 40 65 55 50 35

24 28 68 40

72

62

% with Hot Flashes'

91 01

Volunteers (50) Volunteers (405)

1981 Moore

1981 Sharma Saxena

Clinic population (330)

1977 Goodman Stewart Gilbert

1973 Thompson Hart Durno



Author

Year

1974 McKinlay Jefferys

Study Group" (Total N)

Continued)

(TABLE 1

44 59 61 61

35-60

NA

40-55

Pre (94 Caucasian) Pre (103 Japanese) Post (1 16 Caucasian) Post (107 Japanese) 1-10 yr Post (50)

Pre (135) Pen (135) Post (135)

Non-menopausal = menses in past 2 months Post = no menses 1 yr Post = 2 1 yr past date of last menstrual period Pre = normal menses 1 yr prior Peri = change in menstrual pattern in past year Post = no menses 1 2 yr

U.S.A. (Hawaii, Honolulu) Zimbabwe India (Varnasi City)

,

,,

45-54

Pre (134) Peri (174) 0-1 yr Post (60) 1-5 yr Post (168) 5-9 yr Post (81) >9 yr Post (21)

28 24

10

16

63 59 29

15

18 43

26 4

67

44 93

Pre = menses in last 3 mo Meno = menses in last 3-12 mo Post = no menses 1 yr

11

40-60

England (London)

Scotland (Aberdeen)

Pre (98) Pen (16) 10 yr Post (23)

% with Hot Flashes'


Pre = menses in last 3 mo Meno = menses in past yr, not in last 3 mo Post = no menses 1 yr

Location

Investigator Definitions of Menopausal Statusb

Menopausal Statusb (number of subjects by menopausal status)

Clinic population (47) General population (1118)


1984 Walfisch Antonovsky Maoz

1985 Feldman Voda Gronseth

1985 Berg Hammar

Volunteers (1025)

General population (426) General population (79)

1984 Agoestina van Keep

1984 James et al.

1983 Smith Waters

U.S.A. (Midwest)

Israel (those born in North Africa) Sweden (Linkoping)

Indonesia (West Java)

England (Southharnpton England (Kent)

Post = no menses 1 yr

Pre (130)

Pre = menstruating Post = 20.5 yr after last menstrual period

Pre (163) Post (252)

1 yr Post (118) 2-4 yr Post (303) 5-6 yr Post (74) 9 yr Post (76)

0.5 yr Post (63)

Post (47)

Not defined

Pre Peri Post

0-2 yr Post 3-5 yr Post 6-10 yr Post >10 yr Post

Date of last menstrual period

Pre = regular menses Pen = at least 1 menses past yr Post = no menses 1 yr

Not described

Not defined

15-58

50-52

48-53

40-45 4 1-54 41-54

54-56

53-60

89 82

33 20

41

54 40d 58

53

9 13 12

60 67 68 33

83

0 VI

Canada (Manitoba)

Sweden (Linkoping)

Sweden (Goteborg)

Location

Pre = regular menses for past 12 mo Peri = some change in menstrual pattern in past year Post = no menses 2 1 yr

Several years after last menstrual period

Pre = menses in last 2 mo Peri = menses in 2-5 mo Post = no menses 2 6 mo

Investigator Definitions of Menopausal Statush

Pre (918) Pen (351) Post (722)

40-59

60-62

< 4 yr Post 5-6 yr Post 7-8 yr Post 9- 1 1 yr Post 12-15 yr Post > 16 yr Post

40-60


Pre (640) Pen (58) Post (490)

Menopausal Statush (number of subjects by menopausal status)

1s 38 14 30

32 27 18 17

40d

18 58 60

% with Hot Flashes‘

If a study included both natural and surgically menopausal women, when possible, values for the naturally menopausal women were extracted for this table. If cited data included both naturally and surgically menopausal women, percent of artificially menopausal women is noted; OVX = bilateral ovariectomy; HYS = hysterectomy. Different investigators may use slightly different terminologies, particularly for the perimenopausal period, but to facilitate comparisons in this table data have been designated in 3 categories: premenopausal = normal menses within the past year; peri-menopausal = menstrual cycle within the past year, but not regularly; post-menopausal = no menses for 2 1 year. Percent with hot flashes is for women currently experiencing hot flashes. However, definitions of “current” varied from “within the past 2 weeks” to “within the past year.” Percent approximate from graph NA = not available.


General population (1469) (15% OVX or HY S)

1988 Berg et al.

Kaufert (personal communication)


Author

Year

Study Group“ (Total N)

1986 Hagstad Janson

Continued)

(TABLE 1

Scotland (Aberdeen)

U.S.A. (Los Angeles) U.S.A. (Midwest) Sweden (Goteborg) Sweden (Linkoping)

General population N = 112 Women with U.S.A. Endometriosis (Durham, N = 22 North Carolina) England (London)

General population N = 269”

Hospital patients N = 100

Hospital patients N = 25 General population N = 594’ General population N = 1413“ General population N = 1469”

Thompson et (11.

Richards

Aksel er ul.

Chakravarti et 01.

Defazio et ul.

Feldman et ol.

Hagstad Janson

Berg et (11.

1973

1974

1976

1977

I983

1985

1986

I988

I,

I

I,

,I

?

?

Pre meno

,I

,,

,I

,,

I,

I,

I,

I

Post meno

Pre meno BC users Perimeno

?

?

? ?

Post meno

I

I,

Pre meno

Menopause Status Preop Procedure

ovx

ovx H Y ~

ovx

ovx

ovx

ovx

ovx PartOvx HYS Controls

ovx ovx ovx ovx HYS H Y ~ Artif.

86

63

82

25

II 30 13 20 15 II

16 3 3

17 4 35 56

43

I4 13 18 5 8 18

n for W HF calc

OW

I,

60-62

,,

40-60

26-54

?

57-71

44-68

32-41 33-53 4 1-57 39-62

21-39 21-39 41-48

26-69 26-69 26-69 21-67

40-59

45-55

Age Range

?

?

?

6-8 wk

2-3 4-7 8-13 14-18 20-3 I

0-1 yr

in hospital in hospital 1-6 wk

4-73 mo

16-63 mo

lmmed 6 mo 2 yr lmmed 6 mo 2 yr ?

Time Postop

30

70 65

92

76

0

5

9

I5

91 40

38 33 67

71 75 69 36

75

13 17

50

W Hot Flash Postop

NOTE: ? Information not provided by authors; Meno = menopausal; Hys = hysterectomy, ovaries conserved; Ovx = bilateral ovanectomy with or without HYS; Postop = post surgery; Artif = artificial termination of menses due to surgery, radiation, chemotherapy, etc.; BC = birth control. TOTALnumber includes naturally menopausal women, as described in TABLEI .

England (Oxford)

South Africa (Cape Town)

Clinic patients N = 85

Author

Utian

Study Location

I972

Year

Study Sample

TABLE 2. Studies T h a t Include H o t Flash Prevalence Data for Surgically Menopausal W o m e n

60


cluded that the problems associated with menopause that women report, are influenced by their cultures’ definition of and attitudes towards m e n o p a u ~ e . Yet, ~~~~~-~~ biologists studying menopause have paid scant attention to cultural shaping of the subjective reporting of the variables they are studying, and social scientists have given insufficient consideration to crucial biological and psychological factors. We know that hormones can affect behavior. Conversely, we finally are coming to appreciate the extent to which factors such as stress can modify hormone levels in menopausal women (Ballinger, this volume).36 Hot flashes have been reported in a variety of cultures, including Indian, African, American Indian, Japanese, Indonesian, Mexican American and May a ~ ~ .Japanese ~ ~ , ~and ~ Indonesian - ~ ~ women report far fewer hot flashes than do women from Western (TABLE1). Mayan women in Yucatan, Mexico, do not report any symptoms at menopause other than menstrual cycle irregul a r i t ~ In . ~ Africa, ~ the sweating of hot flashes is sometimes misdiagnosed as malaria.43 As additional groups are studied, the apparent variety of hot flash experiences becomes increasingly evident. Cultures in which women do not commonly report hot flashes present the researcher with an interesting problem. Are the physiological changes that Western cultures find so characteristic of hot flashes truly absent, or are they present but either perceived differently, or not attributed to menopause? Biological, psychological, sociodemographic, and cultural factors are intricately intertwined, and all must be considered if we are to understand the changes occurring at menopause, and the phenomenon of hot flashes.

Age and Menstrual Cycle Status at Onset of Hot Flashes Few investigators have specifically inquired about the age and menstrual cycle status at which hot flashes begin. Thompson and c o - ~ o r k e r sreported ’~ that hot flashes began prior to menopause in two-thirds of the women they studied, but they did not specify the respondents’ age or menstrual condition when hot flashes did ask age at onset of hot flashes and reported that 60% started. Feldman et of those women who were 40-60 years old began having hot flashes when they were between ages 40-50. Hot flashes started before age 41 for 10% of the naturally menopausal women, and 33% of the surgically/artificially menopausal women.

Total Number of Years and Number of Postmenopausal Years of Hot Flashes Information is sparse on the total time over which hot flashes are experienced. The actual length of time hot flashes were experienced was calculated by Feldman et who found that 64% of the 126 women who reported both dates, had hot flashes for 1-5 years, 26% for 6-10 years, and 10% for more than 11 years. Other studies of women under age 60 did not ask for specific dates, so they could report only that hot flashes continued in some women for more than 5 or 6 years.I6,l9 Women over age 60 rarely have been asked about hot flashes. In 1933, the Medical Women’s F e d e r a t i ~ ninterviewed ’~ women aged 29-91, and reported that for most women hot flashes lasted about 2 years, whereas some women experienced hot flashes for 5-10 years. They also found that women in their seventies and eighties reported hot flashes. Berg et confirmed that hot flashes occurred long into the postmenopausal years. In their sample of women 60-62 years old,


61

15% reported having hot flashes 16 years after menopause. The more older women who are included in a study, the greater the potential for a longer number of years of hot flashes to be reported. Frequency of Hot Flashes Hot flash frequency may vary from several a year to many a day, but there are few details on the numbers and age ranges of women so affected, since most studies have examined women 40-60 years old. In an investigation of women aged 45-54, McKinlay and Jefferys found that 70% had daily hot flashes. Thompreported that 7% of women 40-60 years old had many hot flashes a day, 16% had at least one hot flash a day, and 10% had fewer than one hot flash a week. In Feldman et d . ’ s samplez3 of 524 women with hot flashes, 49% reported at least one hot flash per day. For 26%, hot flashes were too few to count. In my physiological studies one woman has been experiencing hot flashes virtually every hour of every day for 10 years, since undergoing ovariectomy at age 48 (Kronenberg, unpublished observation). The range of observed hot flash frequencies presents a challenge to find the common denominator for the varied patterns, and to uncover the mechanisms involved.

Intensity “Intensity” of hot flashes has been defined differently by different investigators. Some use intensity to mean frequency, rating women who have frequent hot flashes as having “severe” hot flashesSz7 Others define intensity as the seventy of sensation of an individual hot flash. Feldman et al.23distinguish between severity and intensity, with severity considered as an overall rating, incorporating frequency, intensity, duration, and degree of body surface involvement of the hot flash.

Hot Flash Pattern Over Time For many women, hot flashes become less frequent and less intense over time. Voda et al. found that for some women (both naturally and artificially menopausal), the frequency of hot flashes decreased over the 3-year period of their study. But this is not always the case. Although hot flashes of naturally menopausal women may continue for many years, women with surgically induced menopause often report particularly unrelenting hot flashes.

Predictors of Hot Flashes Few attempts have been made to identify factors that might predispose women to hot flashes. No significant association has been found between hot flashes and sociodemographic variables such as employment status, social class, age, marital status, domestic workload, or parity.I6 Nor are women with hot flashes distinguishable from those without hot flashes by age at menarche, age at menopause, number of pregnancies, height, or medical problems.29One factor that correlates with the frequency of hot flashes in menopausal women is mean body weight and

62


percent ideal weight. Women with hot flashes had lower mean body weight and percent ideal weight than asymptomatic women.45 The impact of frequent and long-term hot flashes on women's lives both in terms of health and psychosocial effects is not fully known since prevalences alone do not reflect adequately the magnitude and complexity of this problem. More complete and detailed epidemiologic information on hot flashes is required to make an accurate assessment of the impact.

THERMOREGULATORY PHYSIOLOGY

Physiological responses during hot flashes, as manifested by changes in skin temperature, were reported by Reynolds in 1941,46 and Collett in 194tL4' However, it was Molnar's detailed study in 19754xof heart rate, sweating, skin and core temperatures during hot flashes that rekindled interest in this phenomenon; other investigators repeated and extended these observations. Thermoregulatory and cardiovascular changes that accompany a hot flash are now well documented, as illustrated in FIGURE 1.4x-52 Characteristic patterns exist amidst a wide range of individual variability. The sequence of the physiological changes that characterize the hot flash has been refined as additional parameters have been measured. Immediately prior to the onset of a hot flash (5 to 60 seconds), many women experience a premonition (or "aura") of an impending hot flash. It is during this period, prior to the report of the onset of the hot flash, that heart rate and skin blood flow (particular in the fingers and hand) begin to increase. At the start of the hot flash there is a rapid drop in skin resistance (increase in skin conductance). As peripheral blood flow increases (4-30-fold) and heart rate continues to accelerate (8-16 beats per minute), finger temperature rises (I-7°C) and sweating commences. Evaporative cooling may cause the temperature of the wetted skin to drop. Vasodilation and sweating result in heat loss and a drop in internal temperature (O.l-O.9"C), which reaches a nadir about 5-9 minutes after the onset of the hot f l a ~ h . ~If* there - ~ ~ is significant heat loss and core temperature has been lowered, there may be a chill or shivering. Vasoconstriction and an increase in metabolic rate due to the shivering that may occur, facilitate the return of body temperature to n ~ r m a l . ~Blood '-~~ pressure has thus far been measured only intermittently during studies of hot flashes; no change in association with a hot flash has as yet been f ~ u n d . ~ ~ , ~ ' Although sweating and the perception of heat is most intense over the upper part of the body, the temperature of the toes increases concomitantly with finger temperature, and sweating may occur over the lower part of the body as well,48352 demonstrating that a hot flash is a generalized physiological phenomenon. Most hot flash studies have been conducted in a somewhat cool room (2023°C) in order that skin blood vessels will be constricted in the periods between hot flashes. The resulting cooler skin temperature accentuates the vasodilation and the increase in skin temperature that occurs during the hot flash (skin temperature increases during a hot flash in inverse proportion to skin temperature immediately before the hot f l a ~ h . ~The ~ , finger ~ ~ ) is an excellent site on which to monitor hot flash-associated skin temperature changes when ambient temperature is at thermoneutrality or below. Under these conditions, finger temperature typically increases at least at 1"C, and usually more, during a hot flash. However, a 1°C change should not be thought of as the absolute criterion for a hot flash, since the magnitude of the skin temperature response is influenced by several factors,


63

including ambient temperature, peripheral blood flow, and vascular responsiveness of the individual. Hot flashes appear to be the body's response to a sudden, but transient downward resetting of the body's thermostat (temperature set point), which is located in the h y p o t h a l a m ~ s . ~This ~ ~ ~temporary ' alteration of the central thermoregulatory set point would cause the sensation of intense heat, and the activation of heat

+64

I

0

6

I

I

I

I

I

10 16 20 26 30 36 40 4 6

TlME 0 FIGURE 1. Thermoregulatory and cardiovascular changes during a typical hot flash at an ambient temperature of 28 "C. Subjective sensation, blood flow (finger), heart rate (30second averages), skin resistance (chest), internal body temperature (vagina), and skin temperatures (forehead, finger) are depicted.

loss responses, including behavioral adjustments such as removing clothing or seeking a cooler environment, cutaneous vasodilation and sweating, and a resultant fall in core temperature. When the temperature set point returns to normal, the sensation is one of chilliness, since body temperature has fallen below normal. Heat conservation (vasoconstriction), heat production (shivering), and behavioral adjustments are activated to bring body temperature back to normal. This constel-

64


lation of physiological and behavioral changes suggests that a hot flash is an integrated central thermoregulatory event, the pattern of which is the inverse of that which occurs during a f e ~ e r .The ~ ~lingering . ~ ~ question is what initially triggers this series of events. Subjective Report of Hot Flashes

Self-report of hot flashes has been shown, particularly in laboratory settings, to be a valid index of hot flash o c c ~ r r e n c e . ~However, ~ , ~ ~ , ~outside ~ of the laboratory, self-report may be a less accurate hot flash indicator. For example, when women are involved in their normal activities, they may overlook some hot flashes that can be identified if they are wearing portable monitoring e q ~ i p m e n t . ~ ~ (Kronenberg, unpublished data). In addition, during sleep, particularly in a cool room, women may not always be awakened by hot flashes. Some studies suggest that the subjective report of hot flash intensity reflects the magnitude of associated physiological responses. Peak cheek temperaturesg and percent increase in heart rate52have been correlated with peak subjective hot flash intensity. However, sometimes hot flashes can occur with minimal change in the heart rate.55 (Kronenberg, unpublished data) Further, a dissociation of the perception of a hot flash from the physiological changes typically associated with hot flashes has been observed after administration of clonidine to women with a hot flash.60*61 In this situation, skin temperature increases and pulses of luteinizing hormone (LH) continued as if hot flashes were still occurring, yet the women perceived fewer or no hot flashes. The perception of a hot flash is likely the result of a combination of factors, including sweating and the change in heart rate, and probably involves centrally mediated sensations. The subtleties of the psychophysiology underlying hot flashes have yet to be examined. Hot Flashes and Sleep

One of the primary complaints of women with hot flashes is that their sleep is disrupted, as they may awaken several times, drenched in sweat, necessitating a change of bed clothes. This disturbed sleep can lead to fatigue and irritability. The occurrence of electroencephalographically (EEG)-determined nocturnal awakenings in association with hot flashes was documented by Erlik and co-workers.58 Sometimes, however, hot flashes occur throughout the night, as detected by changes in heart rate, skin resistance and skin temperature, but do not cause conscious awakening (unreported hot flashes) despite transient EEG-defined arousals (FIG.2). Treatment with estrogen reduces the number of hot flashes and the frequency of awakenings .58,62,63 Ambient Temperature and Hot Flashes

Ambient temperature influences the intensity and frequency of hot flashes. Women often report that their hot flashes are worse (frequency and intensity) in warm weather. To relieve the discomfort of hot flashes, women may stand in front of an air conditioner or refrigerator, and wear loose, lighter, nonsynthetic clothing; on winter nights they may open windows or walk outside. Hot flash frequency has been positively correlated with outdoor temperature in some

120

r

TIME OF DAY (Horn)

k

FIGURE 2. Pattern of sleep stages, skin resistance, and heart rate for a 12-hour period (subject #A-10). The solid triangles (v) indicate reported hot flashes; open triangles (v) indicate unreported hot flashes. Sleep stages 1 through 4 = NREM sleep, stage 5 = REM (rapid eye movement); absolute clock time is on the abscissa. The sudden drop in skin resistance at about 7:OO AM is due to a change of skin resistance electrodes. This subject went to bed shortly after 1:OO AM and awoke at about 7:30 AM.

k

7 'O0

8

66


others found no such ~ o r r e l a t i o n . ~ However, ~,~~ ambient temperature was not controlled in any of these studies. We have demonstrated a significant reduction in both the frequency and intensity of hot flashes recorded during the daytime in a cool (19*1”C) as compared with a warm (3121°C) room (Kronenberg and Barnard, this volume). Sleeping in a place with a cool ambient temperature may thus decrease hot flash frequency and intensity sufficiently to reduce nighttime awakenings.

CHRONOBIOLOGY OF HOT FLASHES Hot flashes have been described as occurring “sporadically,” “erratically,” * ~ there ~ . ~ ~seems ~ ~ ~ to be a “unpredictably,” and at “irregular i n t e r v a l ~ , ” ~and wide range of hot flash frequencies as determined both subjectively and objectively. Yet, in one of the few investigations to specifically examine the temporal pattern of hot flashes, analysis of daytime hot flashes based on subjective reports of three subjects suggested that hot flashes do not occur randomly.69 That hot flashes occur with some regularity is given support by physiological data from women with frequent hot flashes.57It may be that hot flashes occur with ultradian and/or circadian periodicities. A diurnal pattern of hot flashes has been observed, with fewer flashes occurring during ~ l e e p . The ~ ~ perceived .~~ intensity of hot flashes also exhibits a diurnal rhythmicity, being greater during the night than in the daytime.71However, since hot flashes sometimes occur at night without awakening the individual (FIG.2 ) , objective measurements are crucial to accurately ascertain periodicities. Hot flash patterns differ among women, and within an individual on different days, at different times of the year, or over the course of several years. Perhaps there are monthly or annual cycles of hot flashes, related to changes in endocrine or environmental factors. Premenstrual syndrome-related hot flashes have been described in association with monthly estrogen ~ i t h d r a w a l Air . ~ ~temperature, stress, and placebo effects have been reported to affect the occurrence of hot flashes (Kronenberg and Barnard, this volume).51,59,73-75

ENDOCRINOLOGY OF HOT FLASHES Estrogen Estrogen has long been studied in relation to hot flashes, given the association of hot flashes with menopause, and the menopausally related changes in the level of estrogen. The abrupt onset of hot flashes after bilateral ovariectomy, and the relief of hot flashes with estrogen therapy further suggested a relationship between low plasma estrogen levels (or estrogen withdrawal) and occurrence of hot flashes. While early studies did not demonstrate a significant correlation between levels of estrogen and the occurrence of hot f l a s h e ~ , ~ ~more-recent -I~ studies reported that levels of circulating estrone and estradiol were lower in postmenopausal women with hot flashes than in those with no hot f l a s h e ~ . Estrogen ~~~~~~~’ levels were also found to be lower in premenopausal women with hot flashes than in those without hot f l a ~ h e s .Yet ~ ~ confounding ,~~ observations exist. Throughout the postmenopausal period, estrogen levels remain low, yet some women never have hot flashes, while for others, hot flashes may occur only sporadically, or soon cease. Prepubertal girls have low estrogen levels, but hot flashes are not

67


reported. Further, hot-flash-like episodes are reported during pregnancy, when estrogen level is high, or immediately post partum5' (Kronenberg unpublished observation). Withdrawal from estrogen is a significant factor, as exemplified by postmenopausal women with gonadal dysgenesis. These women, who have never had normal estrogen levels, do not experience hot flashes unless they are first exposed to, and then withdrawn from, estrogen.s4 The specific mechanism of estrogen action in the etiology of hot flashes thus remains to be explained.

Gonadotropins The high gonadotropin levels at menopause were initially thought to play some role in the hot flash phenomenon. However, hot flashes often decline or stop after

Ez ' ' 0

I

I

1100

1200

I I 1300

1400

1500

TIME (hr) FIGURE 3. Serial measurements of finger temperature and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone, and estradiol in an individual subject. Arrows mark the onset of the temperature rises. (From Meldrum ef a/.101Reproduced by permission.)

menopause, despite continued high gonadotropin levels. When LH and folliclestimulating hormone (FSH) levels are decreased by such anti-gonadotropic agents as danazol, hot flashes may persist.84 Examination of the pulsatile pattern of LH revealed a close association between LH pulses and hot flashes (FIG. Yet, a pulsatile pattern of LH is not a necessary concomitant of hot flashes. Hot flashes have been reported in women who have no L H release, such as those with hypophysectomy,8s in pre- or post-menopausal women in whom pulsatile LH release has been suppressed by treatment with a GnRH analogue,86-8sand in women with pituitary insufficiency and h y p o e s t r ~ g e n i s mThus, . ~ ~ L H per se is not the trigger of hot flashes. GnRH in peripheral plasma is elevated prior to the LH pulse associated with a hot flash.90However, women with defects in GnRH synthesis or release (isolated gonadotropin deficiency) who received estrogen treatment had hot flashes when 3).503s2354

68


estrogen was w i t h d r a ~ n In . ~ addition, ~ when GnRH receptors were blocked with a long-acting GnRH antagonist in women who never had hot flashes, L H pulses were abolished, but hot flashes occurred for the first time.92Although GnRH is not the immediate trigger of hot flashes, some believe that it may yet prove to be involved in the mechanism of hot f l a ~ h e s . ~

Catecholamines Early theories about hot flashes proposed an activation of the autonomic nervous system.84 When catecholamines were measured during hot flashes by Casper et no changes in plasma epinephrine (E), norepinephrine (NE), or dopamine were seen. Other investigators sampled more frequently, and demonstrated that epinephrine increased (FIG. 4)52.93and N E decreased during hot flashes.52 Since finger blood vessels are primarily under alpha-adrenergic vasoconstrictor control,94 a decrease in circulating N E during a hot flash would be consistent with the observed rise in finger blood flow. It has been suggested that N E of central nervous system origin may play a role in the genesis of a hot flash. In the brain, N E affects both central thermoregulatory function and neuroendocrine system^.^^-^^

Other Substances Substances that have been measured in the peripheral circulation in association with hot flashes are listed in TABLE3. Beta-endorphin, P-lipotropin (P-LPH), and adrenocorticotropic hormone (ACTH) increase during hot flashes (FIG. as does cortisol, dehydroepiandrosterone (DHEA), and androstened i ~ n e .No ~ ~substance . ~ ~ as yet has been causally linked to hot flashes. 5),993100

Estrogen Reconsidered Estrogen’s role in hot flashes must be further evaluated in light of its influence on thermoregulatory, neural, and vascular systems. Estrogen alters the firing rate of hypothalamic neurons. In particular, it excites and inhibits warm- and coldsensitive neurons, respectively, in the preoptic area of the hypothalamus of rats.IM Estrogen and progesterone play a role in the changes in internal temperature during the menstrual cycle, although the specific effect of estrogen administration on body temperature remains e q ~ i v o c a l Menstrual . ~ ~ ~ ~ ~cycle-related ~~ differences in thresholds for thermoregulatory responses have been demonstrated, and suggest an involvement of ovarian steroids, particularly progesterone. Io9 Perhaps there are hormone-related alterations of thermoregulatory thresholds in menopausal women. Estrogen also acts on the vascular system, where it can modulate arteriolar and venous tone, and thereby alter regional blood flow. In animal studies, estrogen has been shown to affect the number of a-receptors,Il0 and to potentiate the contractile response of blood vessels to vasoactive substances. 1 1 1 ~ 1 1 2Women with hot flashes have a higher forearm blood flow than do those with no hot flashes, and treatment with estrogen results in a drop in forearm blood flow of those with hot flashes.Ii3Both the central and peripheral effects of estrogen are likely to play a role in the mechanism of hot flashes.


69

WOMEN AND HOT FLASHES: A SURVEY In order to obtain more information on factors related to hot flashes, a survey of women with hot flashes and their counterparts with no hot flashes was undertaken by this author. The remainder of this paper is devoted to these findings. This

10,

.. :.. J

..% .-.

19/2&

..-..

-

/.. ......

-.

.is..:*. . ....A,..

.i

-100

80 m 60 40

20

FIGURE 4. Pattern of cardiovascular, thermoregulatory, and endocrine changes for four consecutive hot flashes over a 2-hr period. Changes in sensation (SENS), heart rate, blood flow (finger), sweating rate, temperatures (esophageal, forehead, finger, and ambient), noreRepinephrine (NE), and epinephrine (E) are depicted. (From Kronenberg and Dowr~ey.~' produced by permission.)

survey was initiated to provide information on the "natural history" of hot flashes and the range of hot flash experiences, with the hope of obtaining information that would facilitate physiological studies. Among the goals of this prospective/retrospective study were to examine characteristics of hot flashes, and how they may vary with time of day, season, passage of time, age, and menopausal status.

e 3-

70


TABLE 3. Changes in Hormones and Neurotransmittors during Hot Flashes Substance

Response

Sampling Interval

Reference

Increase Increase Increase Increase Increase Increase Increase Increase Increase

5 rnin 15 min 5 rnin 30 rnin 5 rnin 30-60 sec 3 min 15 rnin 2 min

bio-LH/i-LH

Increase

FSH

No change Slight increase No change No change Increase No change No change

3 min 15 min 5 rnin 5 min 30 min 5 rnin 3 min 15 rnin

GnRH

Increase

10 min

90

Estradiol

No change

5 min

101 101

LH

54

56 101 102

99 52 93 100 103 104

56 54

101 102 99 93 101

Estrone

No change

5 rnin

DHEA

Increase

5 min

101

Androstenedione

Increase

5 min

101

Progesterone

Border line increase

5 rnin

101

Epinephrine

No change Increase Increase No change

5 rnin

54

30-60 sec 3 min 2 rnin

52 93 103

5 rnin 30 rnin 30-60 sec 3 rnin 2 min

54 102 52 93 103

5 min 2 rnin

103

No change No change No change Increase Increase Increase Increase No change Slight increase

5 rnin 30 rnin 15 rnin

54 102 101

5 rnin 5 min 15 rnin 5 min 15 min 2 rnin

101 101 99 105 103

Increase Increase

5 min I5 min

101

Norepinephrine

Dopamine Prolactin

Cortisol

ACTH

No change No change Decrease No change Increase N o change No change

54

101

99

KRONENBERG HOT FLASHES

71

(TABLE3 Continued)

Substance

Response

Sampling Interval

Reference

P-Endorphin

Increase Increase?

5 min 5 min

99 101

P-Lipotropin

Increase

5 min

99

i-Neurotensin

Increase

30-60 sec

52

Growth hormone

Increase

15 min

101

No change No change

15 min

101

Glucose

2 min

103

Glucagon

No change

2 min

103

Insulin

No change

2 rnin

I03

Free fatty acid

Increase

2 min

103

TSH

Aspects of lifestyle and medical and reproductive history were assessed to determine which factors might predispose women to hot flashes or render them resistant, and which might influence the age at onset of hot flashes and the length of time women experience hot flashes.

Participants and Methods The 501 subjects were women who over a 4-month period in 1983-1984 inquired by letter in response to newspaper articles about our work on hot flashes. Questionnaires were sent to 1180 women, with a cover letter inviting participation. Each women was sent two identical questionnaires and was asked to give the second copy to a friend of comparable age, who had not had hot flashes. The respondents are self-selected and self-identified primarily as having hot flashes. The 26-page, self-administered questionnaire consisted of 94 questions, subdivided into five sections: (a) hot flashes, which included a card on which to record time, intensity and duration of current hot flashes for 2 days; (b) medical and gynecologic history, including current health and illness, medications and reproductive system surgery; (c) diet and exercise; (6)sexual activity; and ( e ) dernographic information. To facilitate consistency in interpretation of questions, an introductory page defined pre-, peri- and postmenopause, and explained that the terms hot flush, hot flash, and night sweat should be considered as synonymous. What follows is a partial report on these data, primarily from the hot flash section of the questionnaire.

Definitions The categories of menopausal status were defined as: Premenopausal: Menstrual cycles still occurring regularly and have had a menstrual period within the past 3 months.

LH

c-4

20

_----

40

60

80

1

100

120

140

160

200

minutes

180

I

?20

-0

-50

100

0--0

F

"Yml

FIGURE 5. Plasma levels of adrenocorticotropin (ACTH), p-lipotropin (P-LPH), and p-endorphin (p-EP) (fop)and luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol (F) (bottom) in subject M. M. during observation period. Arrows indicate onset of hot flashes. (From Genazzani et a1.% Reproduced by permission.)

00

50-

100-

FSHm--.r

$-..p. .'3 /-

w

3

G m

m

8

n

* * 5

4 0 5Fl R

si

z

F m


73

Perimenopausal: Last menstrual period occurring more than 3 months ago, but less than 12 months ago. Postmenopausal: Natural: Last menstrual period more than 12 months ago. Artificial: Menopause due to surgical removal of both ovaries or ovarian inactivation by radiation or chemotherapy. A fifth category was created during analysis for women with hysterectomy only: Indeterminate: Women whose uterus has been removed, with ovaries conserved, before their menstrual cycles stopped naturally, and thus, menopausal status could not accurately be determined. Women were also grouped by hot flash status as a “current flasher,” “past flasher,” “never flasher,” or “current and past flasher” (for those whose hot flashes had stopped for some time, spontaneously or with medication, and had now resumed). When referring to all women who have or who ever have had hot flashes, the term “ever flashes” will be used.

Measures Onset of Hot Flashes: Respondents were asked whether they were currently having hot flashes, or had had them in the past, and what date the flashes had started, stopped, andlor resumed. Length of Hot Flashing Period: The time period during which women had hot flashes was calculated from their reported start and stop dates, which, for the “current and past flashers” included at least two periods separated by a flash-free interval. Frequency, Intensity, and Duration of Hot Flashes: Information on the frequency of hot flashes was derived from two parts of the questionnaire. Women were asked to indicate the number of hot flashes they had experienced in the last month as a number per day, per week, per month, or as “some in the last year, but not in the last month”. In addition, respondents completed a prospective 2-day hot flash log in which they recorded the times, intensities and duration of each hot flash over a 2-day period. They were asked to rate hot flash intensity on a scale of 1-10, with 10 being the most intense hot flash they had experienced and to indicate the typical intensity of their flashes as (1) mild, (2) moderate, ( 3 ) severe, or (4) variable. They were also asked how long a typical flash lasts: (1) less than 1 min; (2) 1-5 min; ( 3 ) 6-15 min; (4) more than 15 min; more than 15 min; ( 5 ) variable. Description of a Hot Flash: The questionnaire contained a list of descriptors for the hot flash and the aura, and women were asked to indicate which of the terms described their hot flashes, with a space for their own alternatives. They were also asked whether they could tell when a flash was about to start, or whether they sweat during a hot flash, “always,” “sometimes,” or “never.” Respondents were given a list from which to choose possible precipitants of hot flashes or they could add to that list. Hot Flash Pattern: The women were asked to indicate the time of day at which their hot flashes were most frequent, most intense, and most disturbing (morning, afternoon, evening, during sleep, or no particular time), and whether there was a season (summer, fall, winter, spring) in which hot flashes were either more or less frequent, intense or disturbing. They were also asked whether the pattern (frequency, intensity, duration) of their hot flashes had changed between the time the flashes had started and the present.


74

Results The subjects in this study were primarily women currently having hot flashes, so that much information about their hot flash experience was current. For dates such as onset of hot flashes, the older the women, the more their recall may be questioned. However, women often have the date of menopause or surgery as a point of reference for onset of hot flashes. The results must be viewed acknowledging the limitations inherent in these types of data. It should be emphasized that the subjects are primarily women with hot flashes, and thus the reported percentages are not representative hot flash prevalences. In all, 506 women returned the questionnaire. Although they were from 26 states, most resided in New York, Michigan, New Jersey and California. Ninetyeight respondents were friend-pairs. Friendlcontrol comparisons have not yet been analyzed. Five women were excluded from the final analysis because of reported endocrine probIems. Of the 501 remaining women, 438 women had had hot flashes at some time in their life. Of these women, 341 were currently experiencing hot flashes; 23 women in this subgroup had stopped having hot flashes for a period of time, but were now again experiencing them. This pattern was common in women who used hormone therapy for a period of time and then stopped. TABLE 4.

Sample According to Hot Flash and Menopausal Status Menopausal Status

Hot Flash Status _____

Pre-

Totals

Peri-

Natural

Surgical

Indeterminate

n

Percent

63.4 4.6 19.4 12.6

~

Current only Current + past Past only Never

10 0 9 16

30 2 7 7

172 7 48 33

72 7 16 1

33 I 17 6

318 23 97 63

Total (n)

35

46

260

96

63

50 1

NOTE: Current only = women who are currently having hot flashes; Current + past = women who had hot Rashes some time in the past which stopped for awhile, but have currently resumed; Past only = women who had had hot flashes some time in the past; Never = women who have never had hot flashes.

Ninety-seven women had had hot flashes at some time in the past (“past flasher”) but were not “current flashers,” and 63 women had never experienced hot flashes (‘‘never flashers”). Each woman was classified according to her menopausal status. No one reported having had radiation or chemotherapy. All “artificially” menopausal women were surgically menopausal and are referred to as such. The 63 women of “indeterminate” menopausal status were excluded from analyses involving years postmenopause.

Personal Information Subjects ranged in age from 29 to 82. The age distribution of the participants 6, and hot flash status according to their menopausal status is given in FIGURE with respect to menopausal status in TABLE4. Other characteristics of the respondents are given in TABLE5. The mean age at menopause was 49.5 years for the naturally menopausal women (median age at menopause = 501, and 43.7 years (median = 45 years) for the surgically menopausal women. The sample was


75

largely white (96.4%), married (71%), and working full or part time (56%). Twenty-one percent completed high school with no post-secondary school, 75% had some post-secondary school education, and 4% had not completed high school. Onset of Hut Flashes: The age range over which women began having hot flashes was 20 to 58. For approximately 50% of flashers, hot flashes began before TABLE 5. Characteristics of Respondents

45.9

&

5.0

Age at No. of Onset of Years of Hot Hot Flashes Flashes 42.8 t 6.3 4.0 t 5.4

49.9

f

3.9

46.5

f

4.7 3.6

f

2.9

2

7.1

Menopausal Status Premenopausal Perimenopausal Naturally menopausal Surgically menopausal Indeterminate

Mean Age (yr)

57.1 t 6.1

50

49.45

4.4 7.45

&

6.41 47.5

f

5.4 8.2

53.6

r+_

8.6

45

43.66 k 7.2 9.99

f

8.46 44.6

+.

6.8 8.0 2 7.3

55.7

?

8.2

1 year. Mean +- SD.

a 2

Median" Mean No. of Age at Age at Years Post Menopause Menopause Menopause

&

46.4 +- 7.8 8.8 -+ 10.1


76

50 NONE 40

cn

W IRREGULAR

REGULAR

+

Y

23

30

cn u.

0

20 3

z

10

0

menopause, when their menstrual cycles were still regular or becoming irregular (FIG.7). Most of the remainder reported the onset of hot flashes within a year of menopause, with a small number (n = 18, [of 293)]) whose hot flashes began more than two years after menopause. Are the hot flash episodes of women in their twenties identical physiologically to the hot flashes occurring in peri- or postmenopausal women? Postmenopausal women who report an early age at hot flash onset have experienced the hot flashes of menopause, so perhaps are in a better position to label their early experiences as having been hot flashes. The premenopausal women in this sample (mean age 45.9) are closer in age to perimenopausal women than to younger cycling women so it is not surprising that they report hot flashes. These data confirm and extend other reports that hot flashes often begin before cessation of menses. Length of Hot Flashing Period: This study provides evidence that it is not unusual for women to have hot flashes for more than 20 years. The total time of flashing ranged from a few months to 44 years (FIG. 8). A majority (60%) of the women had thus far experienced hot flashes for < 7 years, and 15% for more than 15 years. Fifty percent of the women who had more than 15 years of hot flashes started having hot flashes when they were between 26 and 35 years old. Of those whose hot flashes began when they were between 45 and 55 years of age, 50% had more than 5 years of hot flashes. Although for some of these women hot flash onset was at an early age due to surgically induced menopause, a number of naturally menopausal women also began flashing at a young age. The women who reported 44 years of hot flashes, had experienced an early menopause (age 31).

77


She took estrogen for many years, but her hot flashes continued, particularly during the weeks she was off estrogen. Since most of the participants were still experiencing hot flashes, the reported number of years of hot flashes are underestimates. Of the women who were “past flashers,” approximately half had their hot flashes suppressed by hormone therapy, while more than one-third indicated that their hot flashes had stopped “spontaneously.” Further, for those whose hot flashes were suppressed for a period of time because of hormone therapy, it is likely that the hot flashes would have continued during that period had they not taken medication. More studies of women ages 60-90 are needed so we can determine the full course that hot flashes may take and to identify factors that may be related. Frequency, Intensity and Duration of Hot Flashes: Frequency, intensity, and duration of hot flashes vaned both within and among individuals. Most (295/341; 87%) of the “current flashers” had daily hot flashes. While about a third of these reported more than 10 hot flashedday, the reported frequency of hot flashes among “ever-flashers” ranged from 5 per year to 50 per day. Women rated the intensity of their typical hot flash as mild, moderate, severe, or variable (FIG.9). More than one-third of the naturally menopausal group reported their hot flashes to be variable in intensity and 26% reported that their hot flashes were severe. The surgical, indeterminate, and premenopausal groups reported predominately severe hot flashes (47.4%, 42.1% and, 36.8%, respectively); about a third of each of these groups reported that their hot flashes vaned in intensity. Penmenopausal women indicated that their hot flashes varied or were

H SURGICAL H INDETER

I

NATURAL

-1.

o

I

+J

Y

6

v

PER1

H PRE

B B ~

4 ~

~

~

~

~

YEARS FIGURE 8. Total years of hot flashes by current menopausal status.

~

I


78

B Moderate

IIB Severe

H Variable

50

40 I-

Z

w

30

w

a 20 10

0 Pre

Peri Natural Surgical MENOPAUSAL STATUS

FIGURE 9. Intensity of hot flashes according to current menopausal status.

moderate in intensity (39% and 3 I%, respectively). We defined “intensity” as referring to individual hot flashes, and agree with Feldman et that the severity of hot flashes somehow reflects an integration of the many components of the hot flash phenomenon. A hot flash was commonly 1-5 minutes long in all menopausal status groups (55.5% of “ever-flashers”). Only 17.4% reported that most hot flashes lasted less than 1 minute, and 5.7% reported that hot flashers were most typically more than 6 minutes long. About 1% reported that hot flashes usually lasted longer than 15 minutes. For 16.4%, hot flashes could not be characterized by one particular length; rather, they varied in duration. Description of Hot Flush: Most women distinguished the premonition that a hot flash was about to begin (the aura) from the hot flash itself. A large proportion of postmenopausal women (41.7% natural, 45.3% surgical) “always” sensed the onset of a hot flash, while only 15.8% of the premenopausal and 23% of the perimenopausal women “always” sensed an impending hot flash. Only a few women “never” sensed an oncoming hot flash (16%), the numbers being highest among pre- and perimenopausal women, and lowest among surgically menopausal women. Descriptions of the aura suggest both physical and psychological components. The most frequent descriptor of the aura was a sense of anxiety (44%), but some mentioned reddening skin, a change in heart rate, or a feeling of heat; others “just know” (32%) when a hot flash is about to begin. The hot flash was described as a sensation of heat, sweating, flushing, anxiety and chills (TABLE6). Women also indicated that during a hot flash they felt irritated, annoyed, or frustrated, and sometimes experienced a sense of panic, a feeling of suffocation, or, occasionally, suicidal feelings. About 42% were embarrassed by their hot flashes. The pre and perimenopausal women were less embarrassed ( 3 I .6% and 28.2%, respectively) than the postmenopausal women (natural, 43.0%; surgical 46.3%).

84.2 47.4 94.7 79.0 36.8 42.1 63.2 47.4 63.2 21.1 57.9 31.6 47.4 10.5 19

(16) (9) (18) (15) (7) (8) (12) (9) (12) (4) (11) (6) (9) (2)

n 87.2 43.6 76.9 76.9 25.6 12.8 43.6 20.5 59.0 12.8 59.0 28.2 38.5 10.3

%

Peri-

+ past”

39

(23) (5) (23) (11) (15) (4)

(8)

(17)

228

(196) (73) (196) (178) (60) (29) (82) (57) (123) (44) (123) (98) (79) (12)

n 93.9 45.3 91.6 84.2 31.6 22.1 47.4 36.8 67.4 23.2 61.1 46.3 44.2 9.5

n

95

(22) (58) (44) (42) (9)

(64)

(89) (43) (87) (80) (30) (21) (45) (35)

Surgical %

flashers are included.

43.0 34.7 5.3

54.0

86.0 32.0 86.0 78.1 26.3 12.7 36.0 25.0 54.0 19.3

(34) (17) (30) (30) (10) (5)

%

n

Natural

Menopausal Status

NOTE:Only respondents who were “current” or “current

Total n

Heat Burning sensation Sweating Flushed Pressure in head Pressure in chest Change in heart rate Change in breathing rate Anxious IIUnauseous Chills/clamminess Embarrassed Depressed Suicidal

%

Pre-

TABLE6. Description of Feeling during a Hot Flash

94.7 42.1 84.2 79.0 24.6 12.3 36.8 31.6 54.4 14.0 47.4 40.4 35.1 1.8

%

57

(54) (24) (48) (45) (14) (7) (21) (18) (31) (8) (27) (23) (20) (1)

n

Indeterminate

88.8 37.9 86.5 79.5 27.6 16.0 40.4 29.0 57.8 19.0 55.3 41.6 37.7 6.4

%

Total

438

(28)

(242) (182) (165)

(83)

(70) (177) (127) (253)

(121)

(379) (348)

(166)

(389)

n

$

sa

X

0

n

3 3 B

0

n

5r:


80

Sweating: Almost all women sweat during hot flashes. This was the most bothersome complaint, since it often required a change of clothing, bed linens, or rolling over to a dry spot on the bed. Only 5% reported that they never sweat during a hot flash. The sweating was localized primarily to the upper body (TABLE 7). Almost two-thirds of premenopausal women reported total body sweating, but fewer peri (25.6%), natural (29%) and surgical (35.8%) women did. Trigger: Hot flashes occurred spontaneously in most women. However, many women reported specific triggers for hot flashes. Stress or emotional situations were cited most often (59%), followed by external heat (44%) and a confining space (38%). A small number of women reported that caffeine (17%) and alcohol (20%) triggered their hot flashes. Pattern of Hot Flashes: For most women there was no time of day that hot flashes were more frequent; however, there were time-of-day differences in hot flash intensity. Pre- and perimenopausal women reported hot flashes to be most intense during sleep (47% and 49%, respectively). A majority of postmenopausal women (natural and surgical) found no particular time of the day when hot flashes were more intense. Nighttime hot flashes were the most disturbing because they caused repeated awakenings. TABLE 7.

Location of Sweating during a Hot Flash (n = 438)

Face/Head Menopausal Status PrePeriNatural Surgical Indeterminate

%

n

Chest

Neck %

n

%

n

Lower Part of Body

~ %

_

n

(9) 47.4 (9) 26.3 ( 5 ) 57.9 (11) 47.4 79.5 (31) 79.5 (31) 69.2 (27) 25.6 (10) 84.2 (192) 73.7 (168) 65.4 (149) 30.3 (69) 84.2 (80) 77.9 (74) 72.6 (69) 29.5 (28) 132) 40.4 (23) (4) 56.1 71.9 141) 4.2

NOTE:Only respondents who were “current” or “current

All over

_

%

63.2 25.6 29.0 35.8 43.9

n

_

n

(12) 19 (10) 39 (66) 228 (34) 95 (25) 57

+ past” flashers are included.

When asked whether they noticed any other pattern with respect to their hot flashes, a small number responded positively. Seven premenopausal women reported hot flashes to be worse at “one particular time” of their menstrual cycle. Ten perimenopausal women reported that hot flashes were most frequent in the intervals when they had no menstrual periods. And 38 postmenopausal women (19 natural, 10 surgical) reported that hot flash frequency varied in a monthly pattern. Most women reported there to be no seasonal change in the frequency, intensity or disturbance of their hot flashes; but for some women, hot flashes were slightly more frequent, intense, and particularly more disturbing during the summer. There was no particular long-term trend in the pattern of hot flashes. Approximately equal numbers of women reported increased as reported decreased frequency of hot flashes in the period since hot flashes had begun; almost twice as many women reported that hot flashes became shorter over time compared with those who said they became longer; and some women reported no discernible change in hot flash pattern. Consultation with a Doctor: Of the 438 “current” or “past” flashers, 340 (78%) consulted a physician for “menopausal problems,” the most common of which was hot flashes ( n = 333), followed by sleep disturbance ( n = 178), depression (n = 141) and vaginal dryness ( n = 140). Of the “never-flashers,’’ 24% consulted a physician, primarily for vaginal bleeding or depression. One hundred


81

women experienced menopausal problems for which they had not seen a doctor, including vaginal dryness ( n = 4 9 , hot flashes (n = 40) and sleep problems (n = 38). SUMMARY

A review of the literature illustrates the many questions about hot flashes that remain unanswered. My survey addresses some of these questions. The prospective and retrospective descriptions of hot flashes provide a more detailed profile of the hot flash than has previously been available. Further, data from this survey demonstrate that while the patterns of hot flashes may be varied, there are commonalities in hot flash physiology and subjective manifestation. The data indicate that hot flashes may start much earlier and continue far longer than is commonly recognized by physicians or acknowledged in textbooks of gynecology. Studies of hot flash duration must control for age or age at hot flash onset, since the older the subjects, the more potential years of hot flashes and the greater the probability of encompassing the entire period of hot flashes. Hot flashes are not static; patterns may change with time. For some women, hot flashes become less frequent and less intense; for others, hot flashes may continue at hourly intervals well into old age. How common these experiences are for women of all ages still needs to be discovered. As expounded by K a ~ f e r t McKinlay,"j ,~~ G ~ o d m a n , ~and ' many others, a greater effort must be made to standardize definitions and question formats as well as to improve methodology in epidemiologic investigations to facilitate comparability between studies and insure that proffered conclusions indeed reflect the questions being asked. Physiological studies are critical counterparts to the epidemiology; yet such studies have been too few. My work, by examining the physiology and psychophysiology of hot flashes, has raised additional questions about central and peripheral inputs that may affect the subjective experience of hot flashes. A more complete understanding of the thermoregulatory, cardiovascular, and psychophysiology of women with hot flashes as compared to women without will facilitate the prediction of who is most likely to be affected and the identification of additional approaches to the management of hot flashes. ACKNOWLEDGMENTS

I would like to thank E. Brickman and S. Mahler for their efforts in analysis of the survey data. D. McMahon and the Irving Center for Clinical Research have also contributed their expertise to the surveys analysis. S. Teitelbaum has provided valuable and greatly appreciated input at all stages of this hot flash research. The many discussions with and comments of R. Barnard and L. Cote are gratefully appreciated. I would especially like to thank J. A. Downey for his longstanding support of this research. Special thanks go to the women who gave so generously of their time and energy by persevering through the time-consuming questionnaire with the hope of contributing to the good of womankind. REFERENCES 1 . GAMBRELL, R . D., JR. 1986. The menopause. Invest. Radiol. 21: 369-378. 2. WHITEHEAD,M. I. 1987. The menopause. Practitioner 231: 37-42. 3. ZICHELLA, L., E. TESSERI, P. FALASCHI, M. GAMBACCIANI, A. CAGNACCI, F. STRI-


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