Old1991   Oldenhave JM. Well-being and sexuality in the climacteric. Academisch Proefschrift Utrecht 1991.

Ale1992   Overgangsjaren: feiten en fabels (1992), Aletta, Centrum voor Vrouwengezondheidszorg, Utrecht i.s.m. Stichting VIDO Nederland. ISBN 90-70617-35-8.

Gav1992   Gavaler JS, Van Thiel DH. The association between moderate alcoholic beverage consumption and serum estradiol and testosterone levels in normal postmenopausal women: relationship to the literature. Alcohol Clin. Exp. Res. 1992;16:87-92.

The major source of endogenous estrogens in postmenopausal women is the aromatization of androgens to estrogens; because alcohol is known to increase aromatization, the relationship between moderate alcoholic beverage consumption and serum estradiol levels was evaluated in 128 normal postmenopausal women. Alcohol intake was based on a composite of self-report and food record information. Among the 78.8% of women reporting alcohol use, weekly intake was 4.8 +/- 0.6 drinks. Among abstainers, estradiol levels were 100.8 +/- 12.1 pmol/liter, significantly lower than in alcohol users, 162.6 +/- 11.9 pmol/liter. Significant bivariate correlations were found between the logarithm of estradiol and total weekly drinks. In multiple linear regression analyses inclusion of alcohol as a variable increased the amount of explained variation in estradiol. Similar findings were demonstrable when the crude estimator of aromatization, the estradiol:testosterone ratio logarithm was the dependent variable. Together, these findings suggest that moderate alcohol use is an important factor for postmenopausal estrogen status and may offer a partial explanation for the reported protective effect of moderate alcohol consumption with respect to postmenopausal cardiovascular disease risk.

Sch1994a   Schwingl PJ, Hulka BS, Harlow SD. Risk factors for menopausal hot flashes. Obstet. Gynecol. 1994;84:29-34.

OBJECTIVE: To find predictors of hot flashes at natural menopause. METHODS: A cross-sectional sample of 334 black and white, naturally menopausal women was selected from a control group in a population-based study of reproductive cancers in central North Carolina. Women reported whether they had experienced hot flashes at the time of menopause. Life-style factors and reproductive histories of those with and without hot flashes were compared. RESULTS: Compared to women who were older at menopause, those reporting natural menopause before age 52 years had a significantly increased probability of having hot flashes (prevalence ratio 1.5, P = .04). Less than a high school education was significantly related to an increased probability of hot flashes (prevalence ratio 1.4, P = .20). There was significant interaction between cigarette smoking and body mass index (BMI), so that thin women who smoked in the premenopausal period were most likely to experience hot flashes (prevalence ratio 1.9, P = .03). Among non-smokers, BMI appeared to have no effect on the probability of hot flashes. Alcohol use, although not statistically significant, suggested a positive relation with hot flashes over and above that incurred from smoking. In addition, menarche before the age of 12 (prevalence ratio 0.6, P = .08) and a history of irregular menstrual cycles (prevalence ratio 0.6, P = .08) were marginally related to a decreased prevalence of hot flashes. Race, parity, and age at first and last pregnancy had no relation to hot flashes. CONCLUSION: Socioeconomic factors and those related to the decline of estrogen production are related to the occurrence of hot flashes at the time of menopause.

Hahn1998a   Hahn PM, Wong J, Reid RL. Menopausal-like hot flashes reported in women of reproductive age. Fertil. Steril. 1998;70:913-8.

OBJECTIVE: To report the occurrence of menopausal-like hot flashes in women of reproductive age (18-45 years). DESIGN: Observational, prospective cohort study with a retrospective survey component. SETTING: Tertiary care premenstrual syndrome (PMS) clinic and university campus. PATIENT(S): Patients with confirmed PMS (n = 157) were compared with those with chronic menstrual cycle-related symptoms (n = 27). Women without menstrual cycle-related symptoms were solicited as controls (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The frequency of episodes of chills and sweats and the magnitude of menstrual cycle-related symptoms were recorded over one cycle using the Prospective Record of the Impact and Severity of Menstrual Symptomatology (PRISM) Calendar. Characteristics of the episodes of chills and sweats were ascertained by a retrospective questionnaire. RESULT(S): In each group, the frequency of episodes of chills and sweats closely patterned the mean daily PRISM Calendar scores. At least one episode of chills and sweats was reported by 83.4% of the PMS group and 81.5% of the chronic group compared with 43.1% of the control group. The mean (+/-SD) number of episodes per cycle was 5.6 +/- 4.9 for the PMS group and 9.5 +/- 9.1 for the chronic group compared with 1.2 +/- 2.0 for the control group (the difference between all means was statistically significant). CONCLUSION(S): Episodes of chills and sweats similar to menopausal hot flashes were commonly reported by women with cyclic and chronic menstrual cycle-related symptoms.

Vand1999a   Van der Feltz-Cornelis CM. Therapieresistente opvliegers bij vrouwen in de overgang: paniekstoornis? Ned. Tijdschr. Geneesk. 1999;143:281-4.

Loc1988   Lock M, Kaufert P, Gilbert P. Cultural construction of the menopausal syndrome: the Japanese case. Maturitas 1988;10:317-32.

Europe and North America have been the focus of most research on the menopause and its symptoms. In this study, in the course of in-depth interviews Japanese physicians and women were asked to describe the menopausal experience. A cross-sectional survey concerning women and their health at midlife was then distributed to 1738 women. The analysis in this paper is based on the replies received from 1141 non-hysterectomized women aged 45-55. Factor analysis was used to group the symptoms these women had experienced in the previous 2 wk. After constructing an index based on the factor scores, one-way analysis of variance was used to examine the relationship between symptom experience and the epidemiological menopausal status as well as the self-defined menopausal status. Symptom experience was always significantly related to self-defined menopausal status.

Bey1986   Beyene Y. Cultural significance and physiological manifestation of menopause: a biocultural analysis. Culture Med. Psychiatr. 1986;19:47-73.

The perception and experiences of menopause vary cross-culturally. However, the lack of physiological symptoms such as hot flashes, in some cultures, calls for more explanations beyond social and cultural factors alone. Like other developmental events, menopause is a biocultural experience. Therefore, research on menopause should consider biocultural factors such as environment, diet, fertility patterns and genetic differences that may be involved in the variations of menopausal experience.

Can1998   Canto de Cetina TE, Canto Cetina P, Polanco Reyes L. Survey of climacteric symptoms in semi-rural areas of Yucatan. Revista de Investigacion Clinica 1998;50:133-5.

OBJECTIVE: To determine the symptoms of climacterium in women from rural areas of Yucatan. MATERIAL AND METHODS: We conducted a transversal study of 202 women in the villages of Seye and Cuzama. A questionnaire on socioeconomic status, and symptoms of the menopause was applied. RESULTS: In both villages, the commonest menopause-related symptoms were backache tiredness in more than half of the women. Sweating and hot flashes were reported by 35% and 31%, respectively. CONCLUSION: Our observations differed from the absence of hot flashes and sweating reported by another group in rural women living in Yucatan (Ref 7).

Ric1997   Richters JMA. Menopause in different cultures. J. Psychosom. Obstet. Gynecol. 1997;18:73-80.

The nature-culture divide of the Western biomedical and feminist models of the menopausal woman is challenged by the presentation of the results of various anthropological studies of the menopausal transition. Perspectives on women’s ageing bodies may differ across cultures. In individual narratives culturally dominant perspectives on women’s ageing bodies may be either reproduced or challenged. Variation in the social position of women is but one of the factors to explain inter- and intracultural differences in the symptomatology and experience of the menopause, and the meaning given to this life-cycle transition. Other factors to be considered in the study of the menopause cross-culturally are psychological factors, genetics, the entire reproductive history including pregnancy and lactation, patterns of menstrual fluctuation throughout a life-cycle, level of physical activity, diet and physical environment. Based on the knowledge currently available no clear conclusions can be drawn with respect to the causal connections between the different factors relating to intra- and intercultural variations or similarities in response to the menopause, and to the possible linkages between the menopause and illnesses of ageing like osteoporosis and heart disease. It is stressed that in future studies serious attention must be paid to the various methodological problems at stake in the cross-cultural study of the experience and symptomatology of the menopause as a biocultural and political process.

Moh1997   Mohyi D, Tabassi K, Simon J. Differential diagnosis of hot flashes. Maturitas 1997;27:203-14.

Objective: The purpose of this study is to present the physiology and differential diagnosis of hot flashes, other than associated with menopause, in order to facilitate the proper evaluation of symptomatic patients with hot flashes.

Study Design: Literature search using Med-Line computer access.

Results: Interest in flushing reaction began in historic times. With the rapidly expanding population of women over the age of 45 and prevalence of hot flashes as menopausal symptoms, physicians need to be aware of other medical conditions which may mimic hot flashes. These include flushing due to systemic diseases, carcinoid syndrome, systemic mast cell disease, pheochromocytoma, medullary carcinoma of the thyroid, pancreatic islet-cell tumors, renal cell carcinoma, neurological flushing, emotional flushing, spinal cord injury, flushing reaction related to alcohol and drugs, flushing associated with food additives, and eating.

Conclusion: There is a wide variety of disease processes that can cause hot flashes. Knowledge of the nature of these disease processes is necessary to quick recognition of patients with hot flashes who do not respond to estrogen replacement treatment, and to facilitate the proper evaluation of atypical patients. 1997 Elsevier Science Ireland Ltd.

Hahn1998b   Hahn PM, Wong J, Reid RL. Menopausal-like hot flashes reported in women of reproductive age. Fertil. Steril. 1998;70:913-8.

OBJECTIVE: To report the occurrence of menopausal-like hot flashes in women of reproductive age (18-45 years). DESIGN: Observational, prospective cohort study with a retrospective survey component. SETTING: Tertiary care premenstrual syndrome (PMS) clinic and university campus. PATIENT(S): Patients with confirmed PMS (n = 157) were compared with those with chronic menstrual cycle-related symptoms (n = 27). Women without menstrual cycle-related symptoms were solicited as controls (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The frequency of episodes of chills and sweats and the magnitude of menstrual cycle-related symptoms were recorded over one cycle using the Prospective Record of the Impact and Severity of Menstrual Symptomatology (PRISM) Calendar. Characteristics of the episodes of chills and sweats were ascertained by a retrospective questionnaire. RESULT(S): In each group, the frequency of episodes of chills and sweats closely patterned the mean daily PRISM Calendar scores. At least one episode of chills and sweats was reported by 83.4% of the PMS group and 81.5% of the chronic group compared with 43.1% of the control group. The mean (+/-SD) number of episodes per cycle was 5.6 +/- 4.9 for the PMS group and 9.5 +/- 9.1 for the chronic group compared with 1.2 +/- 2.0 for the control group (the difference between all means was statistically significant). CONCLUSION(S): Episodes of chills and sweats similar to menopausal hot flashes were commonly reported by women with cyclic and chronic menstrual cycle-related symptoms.

Vand1999b   Van der Feltz-Cornelis CM. Therapieresistente opvliegers bij vrouwen in de overgang: paniekstoornis? Ned. Tijdschr. Geneesk. 1999;143:281-4.

Tata1980a   Tataryn IV, Lomax P, Bajorek JG, Chesarek W, Meldrum DR, Judd HL. Postmenopausal hot flushes: a disorder of thermoregulation. Maturitas 1980 Jul;2(2):101-7

The changes in cutaneous and body temperature and cutaneous conductance during hot flushes in eight postmenopausal women were studied. The vasomotor changes occurred approx. 45 sec after the patients experienced the initial subjective symptoms of the attacks. The rise in skin conductance appeared to be a more reliable index of the flushing episode than did the change in skin temperature. On the basis of the changes recorded it is suggested that the hot flush syndrome may represent a specific thermoregulatory disorder rather than being due to a non-specific central autonomic discharge. The episodes may be triggered by a neuroendocrine imbalance following the disruption of ovarian function and fall in estrogen production. In assessing the frequency and severity of hot flushes, and the effects of treatment, objective measurements of skin and core temperature and skin conductance should replace subjective criteria.

Leus1994   van Leusden HA. The flush revisited (editorial)Eur-J-Obstet-Gynecol-Reprod-Biol. 1994 Dec; 57(3): 137-9

A nadir of LH precedes the onset of the flush and a flush is never seen without an LH pulse. However, af-ter surgical and medical (GnRH agonist) hypophysectomy flushing occurs while LH is absent, thus LH itself is not the cause of the flush. GnRH agonist treatment induces low LH, whereas flushes remain, even when oestrogens are supplemented, suggesting that GnRH itself is the mediator. As flushes are preceded by a spike of LH-RH, GnRH involvement is most likely. Pulsatile administration of GnRH does not induce flushes, whereas continuous administration does. Thus it is the interference with the pulsatile pattern of GnRH that causes flushes. Even high doses of oestradiol during GnRH agonist treatment do not abolish flushes, whereas the alpha 2-adrenergic agonists such as clonidine and alpha-methyldopa abolish flushes during treatment with GnRH agonists. Thus, dysregulation of the GnRH releasing clock center in the nu-cleus arcuatus in the mediobasal hypothalamus is associated with altered central alpha-receptor activity which results in lowering of the set point of the central thermostat and the circulatory changes. The ba-lance of evidence indicates that interference with the pulsatile pattern of GnRH causes the flush.

Lom1991   Lomax P. Pathofysiology of postmenopausal hot flushes. In: Schönbaum E (ed). The climacteric hot flush. Prog Basic Clin Pharmacol 1991: 6:61-82. Karger, Basel.

Tata1980b   Tataryn IV, Lomax P, Bajorek JG, Chesarek W, Meldrum DR, Judd HL. Postmenopausal hot flushes: a disorder of thermoregulation. Maturitas 1980 Jul;2(2):101-7

The changes in cutaneous and body temperature and cutaneous conductance during hot flushes in eight postmenopausal women were studied. The vasomotor changes occurred approx. 45 sec after the patients experienced the initial subjective symptoms of the attacks. The rise in skin conductance appeared to be a more reliable index of the flushing episode than did the change in skin temperature. On the basis of the changes recorded it is suggested that the hot flush syndrome may represent a specific thermoregulatory disorder rather than being due to a non-specific central autonomic discharge. The episodes may be triggered by a neuroendocrine imbalance following the disruption of ovarian function and fall in estrogen production. In assessing the frequency and severity of hot flushes, and the effects of treatment, objective measurements of skin and core temperature and skin conductance should replace subjective criteria.

Loma1993   Lomax P, Schonbaum E. Postmenopausal hot flushes and their management. Pharmacol Ther 1993 Feb-Mar;57(2-3):347-58

Hot flushes are frequently incapacitating to the patient and the severe vasomotor disturbances may seriously impair normal daily life. This review attempts to provide an understanding of the pathophysiology of the hot flush as a basis for rationale therapy for each individual patient. The physiological mechanisms controlling body temperature are discussed briefly, and the changes in the system which precipitate the menopausal hot flush are detailed. The neuroendocrine events leading to the onset of the flushing syndrome are then considered. Finally, the therapeutic strategies which may be used in the management of the affected patient are discussed.

Free1998   Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flashes. Fertil Steril 1998 Aug;70(2):332-7

OBJECTIVE: To determine if increases in core body temperature preceding most hot flashes are caused by increased metabolic rate, peripheral vasoconstriction, or central noradrenergic activation. DESIGN: Laboratory physiological study. SETTING: University medical center. PATIENT(S): Fourteen healthy, postmenopausal women reporting frequent hot flashes. INTERVENTION(S): Data were recorded for 3 hours in a temperature- and humidity-controlled room. MAIN OUTCOME MEASURE(S): Core body temperature, mean skin temperature, respiratory exchange ratio, sternal skin conductance, plasma 3-methoxy-4-hydroxyphenylglycol, and vanillylmandelic acid. RESULT(S): Twenty-nine physiologically defined hot flashes were recorded. Increases in core body temperature, measured with an ingested radiotelemetry capsule, preceded 76% of the flashes. Increased metabolic rate began after increased core temperature. Peripheral vasoconstriction did not occur. Plasma levels of 3-methoxy-4-hydroxyphenylglycol, a metabolite of brain norepinephrine, increased significantly, whereas vanillylmandelic acid, a peripheral metabolite, did not. CONCLUSION(S): Core body temperature elevations preceding menopausal hot flashes are not driven by peripheral vasoconstriction or increased metabolic rate, but probably by a central noradrenergic mechanism.

Fre1989   Freedman RR. Laboratory and ambulatory monitoring of menopausal hot flushes. Psychophysiology 1989;26:573-9.

A large increase in skin conductance activity recorded from the sternum was found during menopausal hot flashes and corresponded well with patient self-reports. The magnitude and time course of this skin conductance change was similar during spontaneous hot flashes recorded in the laboratory, during heat-induced hot flashes, and during those recorded by ambulatory monitoring techniques. This pattern of sternal skin conductance change did not occur in premenopausal women during body heating or ambulatory monitoring. These methods should be useful in research on the etiology and treatment of menopausal hot flashes.

Fre1992   Freedman RR, Woodward S, Norton DAM. Laboratory and ambulatory monitoring of hot flushes: comparison of symptomatic and asymptomatic women. J. Psychophysiol. 1992;6:162-6.

DeB1996   De Bakker IPM, Everaerd W. Measurement of menopausal hot flushes: validation and cross-validation. Maturitas 1996;23:87-98.

Specificity and sensitivity of two physiological markers for hot flushes were investigated. One marker, proposed by Freedman, is an increase of sternal skin conductance, the second marker, proposed by Swartzman, is a physiological profile which consists of skin conductance changes in combination with circulation changes. In our laboratory 20 menopausal women, 15 with frequent hot flushes and 5 without hot flushes, and 5 women with regular menstrual cycles were continuously monitored for 2.5 h on subjective hot flush experience, sternal and palmar skin conductance, dorsal and palmar finger temperature and pulse blood volume. Increase in sternal skin conductance proved to be very specific in contrast to Swartzman’s physiological profile, although it was less sensitive. Receiver operating characteristics revealed that an increase combined with a preceding decrease in sternal skin conductance as most specific for, and most sensitive to, subjectively reported hot flushes. This was confirmed by a cross-validation with 34 “flushing” menopausal women.

Gut1996   Guthrie JR, Dennerstein L, Hopper JL, Burger HG. Hot flushes, menstrual status and hormone levels in a population-based sample of midlife women. Obstet. Gynecol. 1996;88:437-42.

OBJECTIVE: To determine the frequency of hot flushes in a population sample of 453 pre-, peri-, and postmenopausal women (aged 48-59 years), and to investigate the relationship of hot-flush reporting with menstrual status, serum levels of estradiol (E2), inhibin, and FSH, history of premenstrual complaints, and physical and life-style factors. METHODS: We used a population-based sample. Interviews were conducted in the women’s homes. RESULTS: Frequency of hot-flush reporting was associated with menstrual status (P  .001). Twenty-nine percent of women who had more than 3 and less than 12 months of amenorrhea, and 37% of postmenopausal women experienced hot flushes several times a day. In total, 13% of premenopausal women, 37% of perimenopausal women, 62% of postmenopausal women, and 15% of women on hormone therapy reported having had at least one hot flush in the previous 2 weeks. Follicle-stimulating hormone levels were higher in women who experienced hot flushes at least once a day or more (P  .001); E2 levels were higher in women experiencing one or no hot flushes per week (P  .001). The women in the perimenopausal group who experienced hot flushes had higher FSH levels (P = .008) and were more likely to have reported premenstrual complaints at the first interview 3 years earlier (P = .03). In the postmenopausal group, there was no significant difference with any of the variables studied between the women who were experiencing hot flushes and those who were not. CONCLUSION: Reporting of hot flushes is greatest 3 months or more after the final menstrual period. The frequency of hot flushes is associated with increasing FSH, decreasing E2, and a history of premenstrual complaints.

Sta1998a   Staropoli CA, Flaws JA, Bush TL, Moulton AW. Predictors of menopausal hot flashes. J. Womens Health 1998;7:1149-55.

There are limited data on the factors associated with menopausal hot flashes, a common and potentially morbid condition. The objective of this study was to identify predictors of menopausal hot flashes. To meet this objective, 233 naturally perimenopausal or post-menopausal women (ages 45-65) attending a large urban hospital center primary care clinic, mammography unit, or women’s health practice were enrolled. The women responded to a self-administered questionnaire assessing selected demographic factors, reproductive history, and behavioral factors. Sixty-seven percent of respondents experienced hot flashes, with 63% reporting frequent hot flashes (at least one hot flash per day) and 60% with hot flashes describing the hot flashes as severe. Women with hot flashes were significantly more likely to have mothers who experienced hot flashes (OR = 4.4, CI = 2.0-10.0) or to be smokers (OR = 2.0, CI = 1.2-3.5). There were no statistically significant associations between hot flashes and other selected demographic, reproductive, or behavior characteristics. These results reveal that menopausal hot flashes are associated with a maternal history of hot flashes as well as with cigarette smoking. These results may help physicians to counsel their patients about smoking cessation.

Sch1994b   Schwingl PJ, Hulka BS, Harlow SD. Risk factors for menopausal hot flashes. Obstet. Gynecol. 1994;84:29-34.

OBJECTIVE: To find predictors of hot flashes at natural menopause. METHODS: A cross-sectional sample of 334 black and white, naturally menopausal women was selected from a control group in a population-based study of reproductive cancers in central North Carolina. Women reported whether they had experienced hot flashes at the time of menopause. Life-style factors and reproductive histories of those with and without hot flashes were compared. RESULTS: Compared to women who were older at menopause, those reporting natural menopause before age 52 years had a significantly increased probability of having hot flashes (prevalence ratio 1.5, P = .04). Less than a high school education was significantly related to an increased probability of hot flashes (prevalence ratio 1.4, P = .20). There was significant interaction between cigarette smoking and body mass index (BMI), so that thin women who smoked in the premenopausal period were most likely to experience hot flashes (prevalence ratio 1.9, P = .03). Among non-smokers, BMI appeared to have no effect on the probability of hot flashes. Alcohol use, although not statistically significant, suggested a positive relation with hot flashes over and above that incurred from smoking. In addition, menarche before the age of 12 (prevalence ratio 0.6, P = .08) and a history of irregular menstrual cycles (prevalence ratio 0.6, P = .08) were marginally related to a decreased prevalence of hot flashes. Race, parity, and age at first and last pregnancy had no relation to hot flashes. CONCLUSION: Socioeconomic factors and those related to the decline of estrogen production are related to the occurrence of hot flashes at the time of menopause.

Old1993a   Oldenhave A, Jaszmann LJ, Haspels AA, Everaerd WT. Impact of climacteric on well-being. A survey based on 5213 women 39 to 60 years old. Am. J. Obstet. Gynecol. 1993;168:772-80.

OBJECTIVE: Our aim was to assess the influence of the severity of vasomotor complaints, menopausal status, and age on the severity of 21 general complaints considered atypical for the climacteric. STUDY DESIGN: A cross-sectional general population survey was conducted through questionnaires of 5213 women aged 39 to 60 years. Statistical analysis was performed by cross tabulation, analysis of variance, and multiple regression analysis. RESULTS: Severity of vasomotor complaints is related to the severity of all 21 general complaints, most pronounced for tenseness and tiredness. Because menstruating women report more severe atypical complaints than nonmenstruating women with similarly severe vasomotor complaints, the change in prevalence of atypical complaints according to menopausal status is rather small. Adjusted for vasomotor complaints, there is virtually no independent effect of age on atypical complaints. CONCLUSIONS: Severity of vasomotor complaints is related to an overall reduced well-being. When climacteric women are seen for atypical complaints it is vital to assess the severity of vasomotor complaints also because others have shown that the severity of vasomotor complaints is indicative of the rate of climacteric bone loss.

Erl1981   Erli Y, Tataryn IV, Meldrom DR, Lomax P, Bajorek JG, Judd HL. Association of waking episodes with menopausal hot flushes. JAMA 1981;245:1741-4.

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest the menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy.

Pol1998a   Polo-Kantola P, Erkkola R, Helenius H, Irjala K, Polo O. When does estrogen replacement therapy improve sleep quality. Am. J. Obstet. Gynecol. 1998;178:1002-9.

OBJECTIVE: Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved. STUDY DESIGN: Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures. RESULTS: Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p  0.001). The subjects were less tired in the mornings and in the daytime (p  0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75). CONCLUSIONS: Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them.

Pur1995a   Purdie DW, Empson JAC, Crighton C, Macdonald L. Hormone replacement therapy, sleep quality and psychological wellbeing. Br. J. Obstet. Gynaecol. 1995;102:735-9.

OBJECTIVE: To examine the effect of hormone replacement therapy upon sleep quality and duration in postmenopausal women. DESIGN: Randomised, single-blind, placebo-controlled trial. SETTING: Sleep research laboratory. SUBJECTS: Thirty-three healthy postmenopausal women. INTERVENTIONS: Continuous 0.625 mg conjugated equine oestrogens with 0.15 mg cyclic norgestrel taken for 12 days per 28 day cycle. MAIN OUTCOME MEASURES: Occurrence of vasomotor symptoms, polysomnographic sleep stage measures, Stanford sleepiness questionnaire, Crown-Crisp experiential index and the cognitive failures questionnaire. RESULTS: Hormone replacement therapy results in an improvement in menopausal symptoms but not in parameters of sleep quality. Despite this, certain measures of psychological wellbeing showed significant improvement in the hormone replacement therapy group. CONCLUSION: Hormone replacement therapy results in a measurable improvement in physical and psychological welfare, the latter being independent of improvement in sleep quality.

Sha1991   Shaver JLF, Giblin E, Paulsen V. Sleep quality subtypes in midlife women. Sleep 1991;14:18-23.

Summary: Eighty-two midlife women (40-59 years) were classified as poor or good sleepers according to either self-reported sleep quality or a sleep efficiency index (SEI) criterion, for comparison of wakefulness, fragmentation and other somnographic sleep variables as ell as psychological (SCL-90) and somatic symptom distress. When classified solely by self-report, the good and poor sleeper groups did not differ on any somnographic variables but self-declared poor sleepers had higher psychological distress scores than good sleepers (p  0.01). When classified solely by the SEI criterion, the good and poor sleepers did not differ on psychological distress but, as expected, differed on various somnographic wakefulness as well as rapid eye movement and stage 2 sleep variables. Further analysis of four subgroups derived by combining objective and subjective, good and poor sleep scores indicated that 15% of this sample (n = 12) perceived but had no objective evidence of poor sleep, and this group scored highest in psychological distress. Only seven women perceived poor sleep in concert with demonstrating low SEI. They scored highest in menopausal symptoms but not in general psychological distress. Key Words: Women’s sleep - Menopause - Psychological distress.  

Polo1999  Polo-Kantola P, Erkkola R, Irjala K, Helenius H, Pullinen S, Polo O. Climacteric symptoms and sleep quality. Obstet Gynecol 1999;94:219-24

OBJECTIVE: To evaluate the effect of climacteric vasomotor symptoms on sleep quality measured by self-report and polysomnography in postmenopausal women. METHODS: Seventy-one healthy postmenopausal women were recruited, of whom 63 completed the study. Each subject recorded climacteric symptoms and subjective sleep quality for 14 days. Sleep quality was evaluated objectively by all-night polysomnography using the static charge-sensitive bed. RESULTS: During polysomnography, a high frequency of climacteric vasomotor symptoms was not associated with changes in sleep latency, percentage of sleep stages, number of arousals, sleep efficiency, or total sleep time. However, a high frequency of climacteric vasomotor symptoms (range 0-8.9, r = .60, P < .001), somatic symptoms (range 0-5.0, r = .25-.44, P < .05), and mental symptoms (range 0-5.0, r = .41-.51, P < .001) was related to impaired subjective sleep quality. In stepwise regression analysis, 32% of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). High body mass index predicted impaired objective sleep quality, such as prolonged latencies to stage-2 sleep (r = .27, P = .031) and slow-wave sleep (r = .51, P = .003) and decreased oxygen saturations (r = -.54, P < .001). Older women had decreased sleep efficiency (r = -.27, P = .030) and lower oxygen saturations (r = -.36, P = .004). Serum estradiol level had only a minor effect on objective sleep quality. CONCLUSION: Impaired subjective sleep quality associated with climacteric vasomotor symptoms did not manifest as abnormalities in polysomnographic sleep recordings. Body mass index and age appeared to have the strongest effect on objective sleep quality.

Hollander2001 Hollander LE, Freeman EW, Sammel MD, Berlin JA, Grisso JA, Battistini M. Sleep quality, estradiol levels, and behavioral factors in late reproductive age women. Obstet Gynecol 2001;98:391-7

OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35-49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged 35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses. RESULTS: Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for current use of sleep medications. CONCLUSION: Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45-49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.

Nic1996   Nicol-Smith L. Causality, menopause and depression: a critical review of the literature. BMJ 1996;313:1229-32.

Objective To assess whether causal criteria can be used to find out whether there is support in published research for maintaining that meno-pause causes depression.

Design Ninety four articles from 30 years of research examining the relation of natural menopause to depression were traced by using Medline and systematic follow up of reference lists. Specified exclusion and inclusion criteria were applied, and the resulting 43 epidemiological primary research articles were classified and tabulated according to sample and measures used and the researchers’ own conclusion as to whether or not an association had been established. This material was qualitatively evaluated with Hill’s nine criteria for causality.

Result There is insufficient evidence at present to maintain that menopause causes depression. In addition to methodological and statistical problems, a temporal problem in the menopause concept hinders research in this area.

Conclusion Causal criteria can usefully be used to structure a literature review. Further theoretical work is required to integrate standard clinical epidemiological concepts.

Avi1994   Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann. Epidemiol. 1994;4:214-20.

The present article prospectively examines the effect of change in menopause status on depression, while controlling for prior depression. This is a longitudinal follow-up of previous cross-sectional analyses reported by McKinlay, McKinlay, and Brambilla who examined the relative contribution of menopause to depression. The data derive from the Massachusetts Women’s Health Study, a 5-year longitudinal study of a cohort of 2565 women aged 45 to 55 years at baseline (1981 to 1982). Results show that prior depression is the variable most predictive of subsequent depression, as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. Onset of natural menopause was not associated with increased risk of depression. Experiencing a long perimenopausal period (at least 27 months), however, was associated with increased risk of depression. The association between a long perimenopause and depression appeared to be explained by increased menopausal symptoms rather than by the menopause status itself. The observed increase in depression during a lengthy perimenopause appears to be transitory.

Arc1999a   Archer JSM. Relationship between estrogen, serotonin and depression. Menopause 1999;6:71-8.

OBJECTIVE: A limited review of the medical literature was performed to determine whether there is an increase in the prevalence of depressive symptomatology in women undergoing menopause and whether this increase can be related to fluctuating levels of estrogen. In addition, we evaluate the possible effect that estrogen has on the concentrations of neurotransmitters, specifically serotonin, in the central nervous system and the subsequent impact on mood in peri- and postmenopausal women. Finally, we examine whether estrogen replacement therapy is efficacious in the treatment of depression during the climacteric. DESIGN: Limited MEDLINE review of the medical literature on depression in women, the evidence for a serotonergic role in depression, evidence linking estrogen to changes in serotonergic activity and evidence that estrogen therapy can improve depression. RESULTS: Depression is more common in women than in men and seems to be increased at times of changing hormone levels in women. The serotonergic system seems to play a major role in depression, although other neurotransmitters are also involved. Estrogen can alter not just serotonergic activity but also has an impact on the activity of several other neurotransmitters that might result in an antidepressant effect. At this time, estrogen therapy for the treatment of depression in peri- and postmenopausal women may be useful, but confirmatory studies are still lacking. CONCLUSIONS: There is suggestive evidence that estrogen therapy is appropriate treatment for mid-to-moderate depression in peri- and postmenopausal women.

Stu1994   Studd JWW, Smith RNJ. Estrogens and Depression in Women. Menopause 1994;1:333-7.

Depression is twice as common in women as in men, with three peaks of occurrence coinciding with major hormonal changes-premenstrual, postnatal, and climacteric. The following review covers studies of all three peaks and the hormonal treatments used.].

Avi1995   Avis NE, McKinlay SM. The Massachusetts Women’s Health Study: an epidemiologic investigation on the menopause. J. Am. Med. Womens Assoc. 1995;50:45-9

This paper presents findings from the Massachusetts Women’s Health Study (MWHS), one of the largest population-based studies of mid-aged women. A longitudinal study that followed a population-based cohort of women as they proceeded through menopause, the MWHS’s goal was to describe their responses and to identify health-related, life-style, and other social factors that affect this transition. Findings indicate that natural menopause appears to have no major impact on health or health behavior. The majority of women do not seek additional help concerning menopause, and their attitudes toward it are, overwhelmingly, positive or neutral. Physicians treating mid-aged women must be careful not to confuse “menopausal” symptoms with indicators of underlying disease or conditions unrelated to menopause.

Hun1990   Hunter MS. [published erratum appears in Psychosom Med 1990 Jul-Aug;52(4):410] Psychological and somatic experience of the menopause: a prospective study. Psychosom. Med. 1990;357-67.

This study investigates the nature of psychological and somatic symptoms experienced during the menopause and attempts to predict individual differences using a prospective design. Thirty-six women, who were premenopausal during an initial investigation, became peri- or postmenopausal three years later. The Women’s Health Questionnaire, developed specifically for this population, was used to assess general health, beliefs, psychosocial factors, and current symptoms. As expected, vasomotor symptoms were more prevalent in peri- and postmenopausal women. However, significant but small increases in depressed mood were also evident. The results of a stepwise regression analysis indicated that past depression together with cognitive and social factors accounted for 51 per cent of the variance in depressed mood reported by menopausal women. The clinical and theoretical implications are discussed.

Arc1999b   Archer JSM. Relationship between estrogen, serotonin and depression. Menopause 1999;6:71-8.

OBJECTIVE: A limited review of the medical literature was performed to determine whether there is an increase in the prevalence of depressive symptomatology in women undergoing menopause and whether this increase can be related to fluctuating levels of estrogen. In addition, we evaluate the possible effect that estrogen has on the concentrations of neurotransmitters, specifically serotonin, in the central nervous system and the subsequent impact on mood in peri- and postmenopausal women. Finally, we examine whether estrogen replacement therapy is efficacious in the treatment of depression during the climacteric. DESIGN: Limited MEDLINE review of the medical literature on depression in women, the evidence for a serotonergic role in depression, evidence linking estrogen to changes in serotonergic activity and evidence that estrogen therapy can improve depression. RESULTS: Depression is more common in women than in men and seems to be increased at times of changing hormone levels in women. The serotonergic system seems to play a major role in depression, although other neurotransmitters are also involved. Estrogen can alter not just serotonergic activity but also has an impact on the activity of several other neurotransmitters that might result in an antidepressant effect. At this time, estrogen therapy for the treatment of depression in peri- and postmenopausal women may be useful, but confirmatory studies are still lacking. CONCLUSIONS: There is suggestive evidence that estrogen therapy is appropriate treatment for mid-to-moderate depression in peri- and postmenopausal women.

Gon1993   Gonzales GF, Carillo C. Blood serotonin levels in postmenopausal women. Effects of age and serum oestradiol levels. Maturitas 1993;17:23-9.

This study investigated the effect of ageing and reduction in ovarian function on whole blood serotonin levels and the effect of the oestrogen replacement in postmenopausal women on blood serotonin levels. Amenorrheic, natural postmenopausal and ovariectomised women had lower blood serotonin levels than regularly menstruating women. Blood serotonin levels increased after oestrogen replacement in postmenopausal women to values similar to those observed in regularly menstruating women. In ovariectomised women, the blood serotonin levels were inversely correlated with age (P  0.01). In women with different serum oestradiol levels ranging 30-1335 pg/ml, a direct relationship was observed between serum oestradiol levels and whole blood serotonin levels (P  0.001). It was concluded that whole blood serotonin concentration is reduced during menopause by suppression of ovarian function but may also be an effect of ageing.

Gro1996   Groeneveld FPMJ, Bareman FP, Barentsen R, Dokter HJ, Drogendijk AC, Hoes AW. Maturitas 1996;23:293-9.

Objectives: To determine more closely the relationship between vasomotor symptoms, well-being and climacteric status according to the last menstrual bleeding and according to the women themselves. Methods: A population-based cross-sectional study was executed using a postal questionnaire. Well-being of women with and without vasomotor symptoms was compared, for the different menopausal statuses. All 2729 women living in a commuter suburb of Rotterdam aged 45-60 years were approached of whom 1947 (71.3%) responded. Well-being was measured by the Inventory of Subjective Health (ISH) and three subscales of the Sickness Impact Profile (SIP). Results: The results showed that the relationship between vasomotor symptoms and well-being was dependent on climacteric status. Pre- and (middle and late) postmenopausal women with vasomotor symptoms more often experienced a relatively lower level of well-being compared to women without these symptoms. However, when the prevalence of vasomotor symtoms is at its peak, i.e. in late perimenopause, a difference in the level of well-being between women with and without vasomotor symptoms was absent. Conclusions: It is concluded that well-being and vasomotor symptoms were inversely related in all menopausal statuses except for the (late) perimenopausal phase. For this no somatic explanation seems plausible. A more social scientific explanation is suggested.

Dit1991   Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol 1991;78:991-5.

Estrogen treatment of postmenopausal women has been suggested to improve mood and psychological function. However, this remains controversial because previous studies involved heterogeneous groups, were not double blind, and included women who were also experiencing somatic symptoms that were relieved by estrogen. A randomized double-blind study was carried out comparing the effects of placebo and conjugated equine estrogens (0.625 and 1.25 mg) on psychological function over 3 months in 36 asymptomatic women aged 45-60. The tests included the Minnesota Multiphasic , Personality Inventory-168, the Profile of Adaptation to Life, and the Beck Depression Inventory. Memory was assessed directly by the Wechsler Adult Intelligence Scales, measuring both digit span and digit symbol. All women were well-adjusted psychologically. The income management scale of the Profile of Adaptation to Life improved (P less than .05) with estrogen, as did the Beck Depression Inventory (P less than .05), but these results were not dose-related. Memory assessed prospectively by the Wechsler Adult Intelligence Scales was not affected significantly. These results suggest that estrogen use may improve the overall quality of life in postmenopausal women.

Ska2000   Skarsgard C, E Berg G, Ekblad S, Wiklund I, Hammar ML. Effects of estrogen therapy on well-being in postmenopausal women without vasomotor complaints. Maturitas 2000;36:-30.

Objective: To establish whether estrogen treatment affects well-being in postmenopausal women without current or previous vasomotor symptoms. Design: Forty postmenopausal women, aged 45-59 years, without current or previous vasomotor complaints, were included. They were randomized to masked treatment with either transdermal 17beta-estradiol 50 mcg/24 h or to placebo. At baseline and after 12 and 14 weeks of treatment, the women completed a questionnaire which reflects well-being, the Psychological General Well-Being (PGWB) Index. Results: The women scored high on the PGWB Index, both at baseline and after 12 and 14 weeks of treatment. There was no significant difference in well-being according to PGWB Index between the groups treated with estrogen and placebo, neither at baseline, nor after therapy. Furthermore, there was no difference in change during therapy between the treatment groups. Conclusion: There is a gradual decline in estrogen during the climacteric, and it is controversial to which extent this affects women's mental health. The PGWB scores in this study were high before therapy, reflecting that these women without previous or current vasomotor complaints represented a selected sample. Neither short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone acetate during 2 weeks improved well-being in postmenopausal women without vasomotor symptoms who had high well-being at baseline. 

Wu2001a  Wu MH, Pan HA, Wang ST , Hsu CC, Chang FM, Huang KE. Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy. Climacteric 2001;4:314-9.

OBJECTIVE: The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women. METHODS: Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale. RESULTS: Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse. CONCLUSIONS: The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.

Neele2002  Neele SJ; Evertz R; Genazzani AR; Luisi M; Netelenbos C. Raloxifene treatment increases plasma levels of beta-endorphin in postmenopausal women: a randomized, placebo-controlled study. Fertil Steril 2002;77:1110-7    

Maartens2002  Maartens LWF, Knottnerus JA, Pop VJ. Menopausal transition and increased depressive symptomatology. A community based prospective study. Maturitas 2002;42:195-200

 Objective: Prevalence of depression is suggested to be substantially higher in women around menopause. Declining estrogen levels might be an explanation. This study attempts to determine whether depressive symptomatology in healthy women is independently related to menopausal transition. Method: All caucasian women born between 1941 and 1947, living in the city of Eindhoven the Netherlands were invited to take part in a screening program (n = 8098) of whom 78% participated (n = 6648). About 92% returned the questionnaires of which 81% (n = 4975) was fully completed. Women using estrogens and/or having undergone hysterectomy and/or ovariectomy were excluded (43.6%). Of the remaining 2820 women, after 3.5 years, 2748 returned another postal questionnaire, of which 76% was fully completed (n = 2103). Depressive symptomatology was assessed using the Edinburgh Depression Scale (EDS). Independent relationship between an intra-individual change in EDS score during the follow-up period and menopausal transition was analysed by multiple logistic regression (enter as well as stepwise method). Results: Beside the classical determinants of depression (unemployment OR 3.1, CI 1.6-5.8, inability to work OR 1.7, CI 1.0-2.8, financial problems OR 2.9, CI 1.1-7.3 death of a partner OR 2.6, Cl 1.1-6.1, death of a child OR 5.9, CI 1.1-32.1 and a previous episode of depression OR 2.0, CI 1.5-2.7) transition from pre to perimenopause and peri to postmenopause was significantly related to a high increase (>5.4) of the EDS score (OR 1.8, Cl 1.1-3.3 and OR 1.8, Cl 1.5-2.7, respectively). Conclusion: The transition from pre to perimenopause as well as from peri to post-menopause seems to be independently related to a high increase of depressive symptomatology. This suggests that the decrease of ovarian estrogen production is a risk factor for depressive symptomatology

Gre1998   Greene JG. Constructing a standard climacteric scale. Maturitas 1998;29:25-31.

Issues relating to the design of scales and their psychometric properties are discussed in the context of constructing a standard measure of core climacteric symptoms. Seven factor analytic studies of climacteric symptoms are examined to determine whether or not there is sufficient consensus across studies to permit agreement on the symptom content and the structure of such a scale. It is argued that these factor analytic studies do indeed contain sufficient consensus on the basis of which a standard climacteric scale can be constructed. Such a scale is described.

Kup1959   Kupperman HS, Wetchler BB, Blatt MH. Contemporary therapy of the menopausal syndrome. JAMA 1959;171:1627-37.

Bar2001a   Barentsen R. Van de Weijer PHM, Van Gend S, Foekema H. Climacteric symptoms in a representative Dutch population sample. Normative data for the Greene Climacteric scale. Maturitas 2001; 38:123-128.

Objective: To measure climacteric symptoms in a population-based survey as assessed by the Greene Climacteric Scale and to obtain normative data for the total score and subscales (psychological, somatic, vasomotor, and sexual) of the Greene Climacteric Scale. Methods: A sample representative of the Dutch female population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269 women aged 45-65 years) and from the NIPO-CAPI@HOME database (a s ample of 235 women aged 45-65 years). They all filled in the 21 items of the Greene Climacteric Scale. The women were divided in four groups according their menopausal status: premenopausal, perimenopausal, postmenopausal and posthysterectomy. Results: Th e total score of the Greene Climacteric Scale (mean; SD) was in premenopausal women 10.53+/-7.36). The score in perimenopausal women (15.78+/-9.09) and postmenopausal women (15.33+/-9.01) were significant higher than in the premenopause. The same significa n t difference between pre and peri/postmenopausal women was observed in the psychological, somatic and vasomotor subscales. The depression subscale did not change significantly during the menopausal transition. Hysterectomized women had the same score as p o stmenopausal women, reflecting the rather high mean age of the hysterectomized women (55.8 years). Conclusions: Prevalence and intensity of climacteric symptoms as expressed in the Greene Climacteric Scale do increase during the menopausal transition and stay high during the postmenopause. Data presented can be considered normative for the Greene Climacteric Scale in a mainly Caucasian population.

Bar2001b   Barentsen R. Van de Weijer PHM, Van Gend S, Foekema H. Climacteric symptoms in a representative Dutch population sample. Normative data for the Greene Climacteric scale. Maturitas 2001; 38:123-128.

Objective: To measure climacteric symptoms in a population-based survey as assessed by the Greene Climacteric Scale and to obtain normative data for the total score and subscales (psychological, somatic, vasomotor, and sexual) of the Greene Climacteric Scale. Methods: A sample representative of the Dutch female population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269 women aged 45-65 years) and from the NIPO-CAPI@HOME database (a s ample of 235 women aged 45-65 years). They all filled in the 21 items of the Greene Climacteric Scale. The women were divided in four groups according their menopausal status: premenopausal, perimenopausal, postmenopausal and posthysterectomy. Results: Th e total score of the Greene Climacteric Scale (mean; SD) was in premenopausal women 10.53+/-7.36). The score in perimenopausal women (15.78+/-9.09) and postmenopausal women (15.33+/-9.01) were significant higher than in the premenopause. The same significa n t difference between pre and peri/postmenopausal women was observed in the psychological, somatic and vasomotor subscales. The depression subscale did not change significantly during the menopausal transition. Hysterectomized women had the same score as p o stmenopausal women, reflecting the rather high mean age of the hysterectomized women (55.8 years). Conclusions: Prevalence and intensity of climacteric symptoms as expressed in the Greene Climacteric Scale do increase during the menopausal transition and stay high during the postmenopause. Data presented can be considered normative for the Greene Climacteric Scale in a mainly Caucasian population.

Bar2001c   Barentsen R. Van de Weijer PHM, Van Gend S, Foekema H. Climacteric symptoms in a representative Dutch population sample. Normative data for the Greene Climacteric scale. Maturitas 2001; 38:123-128.

Objective: To measure climacteric symptoms in a population-based survey as assessed by the Greene Climacteric Scale and to obtain normative data for the total score and subscales (psychological, somatic, vasomotor, and sexual) of the Greene Climacteric Scale. Methods: A sample representative of the Dutch female population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269 women aged 45-65 years) and from the NIPO-CAPI@HOME database (a s ample of 235 women aged 45-65 years). They all filled in the 21 items of the Greene Climacteric Scale. The women were divided in four groups according their menopausal status: premenopausal, perimenopausal, postmenopausal and posthysterectomy. Results: Th e total score of the Greene Climacteric Scale (mean; SD) was in premenopausal women 10.53+/-7.36). The score in perimenopausal women (15.78+/-9.09) and postmenopausal women (15.33+/-9.01) were significant higher than in the premenopause. The same significa n t difference between pre and peri/postmenopausal women was observed in the psychological, somatic and vasomotor subscales. The depression subscale did not change significantly during the menopausal transition. Hysterectomized women had the same score as p o stmenopausal women, reflecting the rather high mean age of the hysterectomized women (55.8 years). Conclusions: Prevalence and intensity of climacteric symptoms as expressed in the Greene Climacteric Scale do increase during the menopausal transition and stay high during the postmenopause. Data presented can be considered normative for the Greene Climacteric Scale in a mainly Caucasian population.

Bar2001d   Barentsen R. Van de Weijer PHM, Van Gend S, Foekema H. Climacteric symptoms in a representative Dutch population sample. Normative data for the Greene Climacteric scale. Maturitas 2001; 38:123-128.

Objective: To measure climacteric symptoms in a population-based survey as assessed by the Greene Climacteric Scale and to obtain normative data for the total score and subscales (psychological, somatic, vasomotor, and sexual) of the Greene Climacteric Scale. Methods: A sample representative of the Dutch female population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269 women aged 45-65 years) and from the NIPO-CAPI@HOME database (a s ample of 235 women aged 45-65 years). They all filled in the 21 items of the Greene Climacteric Scale. The women were divided in four groups according their menopausal status: premenopausal, perimenopausal, postmenopausal and posthysterectomy. Results: Th e total score of the Greene Climacteric Scale (mean; SD) was in premenopausal women 10.53+/-7.36). The score in perimenopausal women (15.78+/-9.09) and postmenopausal women (15.33+/-9.01) were significant higher than in the premenopause. The same significa n t difference between pre and peri/postmenopausal women was observed in the psychological, somatic and vasomotor subscales. The depression subscale did not change significantly during the menopausal transition. Hysterectomized women had the same score as p o stmenopausal women, reflecting the rather high mean age of the hysterectomized women (55.8 years). Conclusions: Prevalence and intensity of climacteric symptoms as expressed in the Greene Climacteric Scale do increase during the menopausal transition and stay high during the postmenopause. Data presented can be considered normative for the Greene Climacteric Scale in a mainly Caucasian population.

Jas1969   Jaszmann L, Van Lith ND, Zaat JCA. The perimenopausal symptoms. Med. Gynaecol. Sociol. 1969;4:268-77.

Summarizing Table 1 to 7, the following conclusions can be drawn: 1. No significant difference can be shown between light, normal and heavy women with respect to the frequency of climateric complaints. 2. An overall difference can be demonstrated, but no interaction, with respect to the following complaints: a. number of pregnancies: women who had never been pregnant have fewer complaints than women who had been pregnant once or more often (P=0.03). b. age at final pregnancy: if the age at final pregnancy was relatively high ( 40) it appeared that there were fewer complaints than when the final pregnancy had been at a lower age (P=0.001). c. annual financial income: women from the higher income brackets had just sihnificantly fewer complaints than women from the lower income group (P=0.05). d. education: women with only primary education had more complaints than women who had enjoyed further education (P=0.001). e. marital status: married women had more complaints than single women (P=0.01) The fact that for the above variables no interaction was found, means that no evidence was found that the differences are dependent on the menopausal stage. 2. The age at menarche showed an interaction (P=0.02) with the menopausal stage, as is illustrated in Table 1. It is emphasized that in the foregoing the variables were analysed one-dimensionally. It is clear that some variables are highly correlated therefore one and the same difference may be found in several ways. The conclusion that fewer complaints were reported by women who were never pregnant than by women who had been pregnant once or several times (conclusion a.) in fact conveys to a large extent the same information as: married women appeared to have more complaints than single women (conclusion c.).

Old1993b   Oldenhave A, Jaszmann LJ, Haspels AA, Everaerd WT. Impact of climacteric on well-being. A survey based on 5213 women 39 to 60 years old. Am. J. Obstet. Gynecol. 1993;168: 772-80.

OBJECTIVE: Our aim was to assess the influence of the severity of vasomotor complaints, menopausal status, and age on the severity of 21 general complaints considered atypical for the climacteric. STUDY DESIGN: A cross-sectional general population survey was conducted through questionnaires of 5213 women aged 39 to 60 years. Statistical analysis was performed by cross tabulation, analysis of variance, and multiple regression analysis. RESULTS: Severity of vasomotor complaints is related to the severity of all 21 general complaints, most pronounced for tenseness and tiredness. Because menstruating women report more severe atypical complaints than nonmenstruating women with similarly severe vasomotor complaints, the change in prevalence of atypical complaints according to menopausal status is rather small. Adjusted for vasomotor complaints, there is virtually no independent effect of age on atypical complaints. CONCLUSIONS: Severity of vasomotor complaints is related to an overall reduced well-being. When climacteric women are seen for atypical complaints it is vital to assess the severity of vasomotor complaints also because others have shown that the severity of vasomotor complaints is indicative of the rate of climacteric bone loss.

Mat1990   Matthews KA, Wing RR, Kuller LH, Meilahn EN, Kelsey SF, Costello EJ, Caggiula AW. Influences of natural menopause on psychological characteristics and symptoms of middle-aged healthy women. J. Consult. Clin. Psychol. 1990;58:345-51.

We investigated the psychological and symptom consequences of the natural menopause in a longitudinal study of 541 initially premenopausal healthy women. All women were given an extensive evaluation at baseline. After 3 years of follow-up, 69 women ceased cycling for 12 months; another 32 women had ceased cycling and had taken hormone replacement therapy for a total of 12 months. These women were reevaluated in a clinic examination identical with the baseline examination, as were 101 age-matched premenopausal control women. Comparison among groups at the baseline and follow-up examination showed that natural menopause led to few changes in psychological characteristics, with only a decline in introspectiveness and an increase in reports of hot flashes being apparent. We conclude that natural menopause did not have negative mental health consequences for the majority of middle-aged healthy women.

Maa2000   Maartens LW, Leusink GL, Knottnerus JA, Pop VJ. Hormonal substitution during menopause: what are we treating. Maturitas 2000;34:113-8.

OBJECTIVES: It is suggested that during menopausal transition, women with vasomotor symptoms benefit from HRT, (hormone replacement therapy) whereas, the use of HRT for other cognitive-vegetative symptoms is questionable. METHODS: The occurrence of menopausal complaints and depressive symptoms was assessed cross-sectionally in 5896 Dutch Caucasian women (47-54 years) of a large community sample in the city of Eindhoven, The Netherlands. Menopausal complaints were assessed using a 22 items self-rating scale (consisting of a vasomotor, uro-genital and a cognitive-vegetative subscale ). Depressive symptoms were assessed using the Edinburgh depression scale (EDS). Differences in mean scores were analysed between groups using ANOVA. The independent relationship of depressive symptoms to the intensity of menopausal complaints was assessed, by multiple linear regression analysis. RESULTS: Women using HRT showed the highest scores on all subscales. Oral contraceptive users had significantly lower scores on the vasomotor subscale compared to HRT users and to non users. Depressive symptoms contributed the most, to the explained variance on scores on the menopausal subscales. CONCLUSIONS: Women during menopause presenting several complaints, other than vasomotor origin might be suffering from underlying depression which makes it questionable to prescribe HRT for the latter symptoms.

Buk1995a   Bukovsky I, Halperin R, Schneider D, Golan A, Hhertzianu I, Herman A. Ovarian function following abdominal hysterectomy with and without unilateral oophorectomy. Eur. J. Obstet. Gynecol. Reprod. Biol. 1995;58:29-32.

There is no consensus concerning optimal adnexal surgery during abdominal hysterectomy, when continued hormonal function is desired, associated with reduced sequelae in the future. The aim of the study was to compare residual ovarian function following abdominal hysterectomy with preservation of one or both ovaries, in a prospective randomized study. Forty patients were allocated randomly and sequentially into two groups: those undergoing abdominal hysterectomy with unilateral oophorectomy, and those undergoing abdominal hysterectomy only. Ovarian function was evaluated by measuring FSH, TLH and E2 before, and 1 week, 1 month, 3 months and 6 months after the operation. Thirty-five percent of the patients undergoing abdominal hysterectomy with unilateral oophorectomy demonstrated impaired ovarian function 6 months after the operation. None of the patients with both preserved ovaries showed impaired ovarian function 6 months later. Therefore, when continued ovarian function following abdominal hysterectomy is desired, preservation of both ovaries seems to be more beneficial.

VanG1996a   Van Geelen JM, van de Weijer PHM, Arnolds HTh. Urogenitale verschijnselen en hinder daarvan bij thuiswonende Nederlandse vrouwen van 50 tot 75 jaar. Ned. Tijdschr. Geneesk. 1996;140:713-6.

Doel: Vaststellen van de prevalentie van urogenitale verschijnselen en de mate van hinder daarvan bij vrouwen in de leeftijd van 50 tot 75 jaar. Opzet: Dwarsdoorsnede-onderzoek. Plaats: Landelijk onderzoek. Methode: Een representatieve steekproef van 2159 thuiswonende vrouwen in de leeftijd 50 tot 75 jaar werd getrokken uit een bestand van een onafhankelijk onderzoeksbureau. De steekproef was representatief voor de Nederlandse bevolking met betrekking tot leeftijd, burgerlijke staat, opleidingsniveau en menopauzale leeftijd. De vrouwen kregen een vragenlijst toegestuurd met 40 vragen over vaginale atrofie, mictie/incontinentie en blaasontsteking. Resultaten: De respons was 81.6% (1761 evalueerbare vragenlijsten). De prevalentie van 1 of meer verschijnselen van vaginale atrofie bedroeg 27%, van mictieklachten, onwillekeurig urineverlies en recidiverende urineweginfecties 36%. Vaginale droogheid en onwillekeurig urineverlies namen lineair af bij volgende leeftijdscategorieen. Ongeveer de helft van de vrouwen met urogenitale verschijnselen ondervond hiervan hinder/veel hinder: 1 op de 3 consulteerde hiervoor de huisarts. De urogenitale verschijnselen hingen niet samen met eerdere uterusextirpatie, maar de hinder was wel groter. Conclusie: De prevalentie van 1 of meer urogenitale verschijnselen bij vrouwen in de leeftijd van 50 tot 75 jaar was hoog: 47%. Van deze groep ondervond 40 tot 60% in meer of mindere mate hinder, doch slechts een minderheid consulteerde hiervoor de huisarts. In de komende decennia zullen deze urogenitale problemen waarschijnlijk nog toenemen.

Miod1998   Miodrag A, Castleden CM, Vallance TR. Sex hormones and the female urinary tract. Drugs 1988;36:491-504.

Symptomatic clinical changes and urodynamic changes are apparent in the female urinary tract system during pregnancy, the menstrual cycle and following the menopause. The sex hormones exert physiological effects on the female urinary tract, from the ureters to the urethra, with oestrogens having an additional influence on the structures of the pelvic floor. High affinity oestrogen receptors have been identified in bladder, trigone, urethra and pubococcygeus muscle of women. Oestrogen pretreatment enhances the contractile response of animal detrusor muscle to alpha-adrenoceptor agonists, cholinomimetics and prostaglandins, as well as enhancing the contractile response to alpha-agonists in ureter and urethra. Progesterone on the other hand decreases tone in the ureter, bladder and urethra by enhancing beta-adrenergic responses. The dependence on oestrogens of the tissues of the lower urinary tract contributes to increased urinary problems in postmenopausal women. Urinary symptoms due to atrophic mucosal changes respond well to oestrogen replacement therapy. However, because they recur when treatment is stopped, continuous therapy with low dose natural oestrogens is recommended. Oestrogens may be of benefit in postmenopausal women with stress incontinence, but the doses necessary for clinical effect are higher than for the treatment of atrophic urethritis. The practice of adding a progestagen to long term oestrogen therapy to reduce the risk of endometrial carcinoma may, however, exacerbate stress incontinence by decreasing urethral pressure. Cyclical therapy with oestrogens may therefore be more appropriate particularly in women who are not suitable for surgery or have a mild degree of stress incontinence, along with other conservative measures such as pelvic floor exercises and alpha-adrenoceptor agonists. The place of oestrogen therapy in motor urge incontinence has not been determined. The risk of developing endometrial carcinoma as a result of long term high dose oestrogen replacement therapy must be borne in mind but remains to be clarified. However, oestriol has less of a uterotrophic effect compared to other oestrogens in standard therapeutic doses and is to be preferred. Side effects are usually dose related and tend not to be a problem with low dose therapy.

VanG1992   Van Geelen JM, Rekers H. Incontinentie in de postmenopauze. Ned. Tijdschr. Obstet. Gynaecol. 1992;105:27-9.

De gevolgen van oestrogeendeficientie op de lagere urinewegen zijn minder algemeen bekend dan de vasomotore symptomen ten tijde van de overgang en de latere effecten op skelet en hart-vaatstelsel. Toch krijgen veel vrouwen na de overgang te maken met urogenitale klachten in de een of andere vorm. In een recent epidemiologisch onderzoek werd een duidelijke relatie vastgesteld tussen de overgang en het optreden van incontinentieklachten. Ook werd een duidelijk verband gevonden tussen incontinentie en andere urogenitale klachten.

VanG1996c   Van Geelen JM, van de Weijer PHM, Arnolds HTh. Urogenitale verschijnselen en hinder daarvan bij thuiswonende Nederlandse vrouwen van 50 tot 75 jaar. Ned. Tijdschr. Geneesk. 1996;140:713-6.

Doel: Vaststellen van de prevalentie van urogenitale verschijnselen en de mate van hinder daarvan bij vrouwen in de leeftijd van 50 tot 75 jaar. Opzet: Dwarsdoorsnede-onderzoek. Plaats: Landelijk onderzoek. Methode: Een representatieve steekproef van 2159 thuiswonende vrouwen in de leeftijd 50 tot 75 jaar werd getrokken uit een bestand van een onafhankelijk onderzoeksbureau. De steekproef was representatief voor de Nederlandse bevolking met betrekking tot leeftijd, burgerlijke staat, opleidingsniveau en menopauzale leeftijd. De vrouwen kregen een vragenlijst toegestuurd met 40 vragen over vaginale atrofie, mictie/incontinentie en blaasontsteking. Resultaten: De respons was 81.6% (1761 evalueerbare vragenlijsten). De prevalentie van 1 of meer verschijnselen van vaginale atrofie bedroeg 27%, van mictieklachten, onwillekeurig urineverlies en recidiverende urineweginfecties 36%. Vaginale droogheid en onwillekeurig urineverlies namen lineair af bij volgende leeftijdscategorieen. Ongeveer de helft van de vrouwen met urogenitale verschijnselen ondervond hiervan hinder/veel hinder: 1 op de 3 consulteerde hiervoor de huisarts. De urogenitale verschijnselen hingen niet samen met eerdere uterusextirpatie, maar de hinder was wel groter. Conclusie: De prevalentie van 1 of meer urogenitale verschijnselen bij vrouwen in de leeftijd van 50 tot 75 jaar was hoog: 47%. Van deze groep ondervond 40 tot 60% in meer of mindere mate hinder, doch slechts een minderheid consulteerde hiervoor de huisarts. In de komende decennia zullen deze urogenitale problemen waarschijnlijk nog toenemen.

Reke1992   Rekers H, Drogendijk AC, Valkenburg HA, Riphagen F. The menopause, urinary incontinence and other symptoms of the genito-urinary tract.Maturitas 1992;15:101-11.

In a study on incontinence and other symptoms of the genito-urinary tract in postmenopausal women covering their prevalence, consequences and predisposing factors, the prevalence of incontinence was found to be 26.4%. Daily incontinence was present in postmenopausal women more than twice as often as before the menopause (P  0.05). The frequency of medical consultation for such incontinence was low; only 26.1% of the postmenopausal women had ever seen their doctor about it. Urgency, nocturia and dyspareunia were more prevalent in postmenopausal women, while vaginal itching and discharge were more frequent in premenopausal women (P  0.05). The prevalence of incontinence and the other genito-urinary symptoms was higher after surgical than after natural menopause. Multivariate analysis showed the menopause to be the only factor that contributed significantly to the onset of incontinence (P  0.001).  

Sherburn2001  Sherburn M, Guthrie JR, Dudley EC, O'Connell HE, Dennerstein L. Is incontinence associated with menopause? Obstet Gynecol 2001;98628-33

OBJECTIVES: To estimate (1) the prevalence of urinary incontinence in a population-based sample of Australian women aged 45-55 and to identify the factors associated with urinary incontinence; (2) the incidence of urinary incontinence over a 7-year follow-up period and to identify whether the transition from pre- to postmenopause is associated with the development of urinary incontinence. METHODS: This was a cross-sectional study of 1897 women and a 7-year longitudinal follow-up of 373 of these women who were premenopausal at baseline. Annual interviews and physical measurements were taken in their homes. RESULTS: Cross-sectional: the prevalence of urinary incontinence was 15%; multivariate analysis found that urinary incontinence patients were significantly more likely than those without incontinence to have higher body mass index (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.15, 1.95), have had gynecologic surgery (OR 2.17, 95% CI 1.42, 3.32), report urinary tract infections (OR 4.75, 95% CI 2.28, 9.90), diarrhea or constipation (OR 1.95, 95% CI 1.27, 3.00), and have had three or more children (OR 1.47, 95% CI 1.06, 2.05). Longitudinal: during the 7-year follow-up, the average prevalence of urinary incontinence was 18% and the overall incidence 35%. Women who experienced a hysterectomy during the follow-up period had a higher incidence. CONCLUSION: Urinary incontinence in middle-aged women is more closely associated with mechanical factors than with menopausal transition.

Brin1987   Brincat M, Kabalan S, Studd JW, Moniz CF, de Trafford J, Montgomery J. A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman. Obstet. Gynecol. 1987;70:840-5.

The skin collagen content, skin thickness, metacarpal index, and forearm bone mineral content in postmenopausal women showed a similar decline of between 1-2% per year after the menopause. All four parameters showed a decline that was significant when compared with the years from the menopause. Significant correlations between all four parameters suggest that a similar pathology causes the decrease in bone mass and skin thicknes - a decline in the connective tissue element that is common to both bone and skin.

Cast1992   Castelo Branco C, Duran M, Gonzalez Merlo J. Skin collagen changes related to age and hormone replacement therapy. Maturitas. 1992 Oct; 15(2): 113-9.

A total of 76 nulliparous women who had been hospitalized for minor operations, classified according to age group (by decade from 20s to 60s) and 118 postmenopausal women randomly allocated to one of four groups were studied. In all, 312 skin biopsies were taken from the lower abdomen at 0 and 12 months and the skin collagen changes noted. Collagen content decreased significantly with age beyond the 40s (P  0.001) and after the menopause (P  0.01). The decrease was preventable by the use of hormone replacement therapy. All the therapeutic regimens induced increases in skin collagen content, whereas in the control group a significant decrease was observed (P  0.05).

Mesc1994   M. Meschia, F. Bruschi, F. Amicarelli, P. Barbacini, G.C. Monza, P.G. Crosignani. Transdermal Hormone Replacement Therapy and Skin in Postmenopausal Women: A Placebo Controlled Study Menopause 1994;1:79-82.

It has been shown that skin collagen decreases in the years after menopause and that oral estrogen replacement therapy is effective in preventing the loss of skin collagen content. Skin thickness, measured radiologically, is a cheap, noninvasive measure of skin