Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

雌激素替代治疗与老年痴呆

老年性痴呆症是随年龄增长发生的由于智力和记忆力严重受损而影响到生活不能自理的综合症。随着人口的老龄化，老年性痴呆在许多发达国家已成为严重的社会卫生难题，从而受到重视。近年发现，绝经后妇女雌激素替代治疗（ＥｓｔｒｏｇｅｎＲｅｐｌａｃｅｍｅｎｔＴｈｅｒａ...     

Bone density patterns after normal and premature menopause

Objectives: The investigation of the effect of time and type of menopause on bone mineral density (BMD) at different ages. Methods: Five hundred and fourteen women, who had never received any hormonal substitution were studied in a cross-sectional design: 177 with normal (NMP), 210 with surgical (SUMP) and 127 with premature natural (EMP) menopause. Age at menopause was 49.1±3.9, 38.3±4.7 and 38.1±4.2 years (mean±1 S.D.), respectively. BMD was measured at L2–L4 vertebrae and proximal femur by the DEXA method. Results: EMP women presented significantly lower vertebral BMD than NMP women in the 45–55-years segments (P<0.001), but did not differ from SUMP women. This group exhibited lower vertebral BMD than NMP between 45 and 50 years (P<0.001). Regarding femoral neck, EMP women exhibited lower values than SUMP in the 45–50 and 55–65 age segments (P<0.001) whereas SUMP women presented significantly higher BMD values than NMP women after 55 years of age (P<0.001). The percentages of women with vertebral BMD (T-score values) in the osteoporotic range were significantly greater in EMP compared with either NMP or SUMP groups (both P<0.001) whereas in femoral neck lower in SUMP than the other two categories. Conclusions: Women with either natural or surgical premature menopause exhibit lower BMD of trabecular bone compared with normal menopause women at the age segments 45–55 and 45–50, respectively. However, surgical menopause women exceed normal menopause women in their mixed bone BMD values after 60 years as well as premature natural menopause women at almost all age segments.     

The effects of oestrogen therapy on the sex life of post-menopausal women

The literature concerning sexual behaviour around the time of the menopause is reviewed. Mentioned is a decline in sexual activity and satisfaction in women which is attributed to the changes in the women themselves, and not merely a reaction to the decline in the sexual capacity of their husbands.

Forty women were treated during 1 yr with oestrogens. The eventual effect of this treatment on sexual activity and satisfaction was investigated and compared with a group who had undergone partial treatment only. The results show that in the completely treated Group A, symptoms such as hot flushes and depression diminished, and the pain of sexual relations was relieved. As a consequence of this improvement, coital activity and satisfaction were more gratifying. The partially treated Group B showed a clear decline in sexual activity and in sexual satisfaction.     

Early impact of hormone replacement therapy on vascular hemodynamics detected via ocular colour Doppler analysis

Objective: To determine the effects of hormone replacement therapy (HRT) on ocular blood flow.

Study design: In a prospective controlled study, 40 healthy women who presented to the menopause clinic between December 2000 and December 2001 were randomly assigned into the study. The HRT-receiving group was administered estradiol 17-valerate 2 mg the first 11 days, and estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg the next 10 days of the monthly cycle for 6 months. The control group did not receive any HRT for 6 months. The ocular colour Doppler analysis were performed at baseline and after 3 and 6 months. The ocular Doppler analysis was performed in the first half of the cycle in the HRT-receiving group.

Results: Central retinal artery and ophthalmic artery basal Doppler index (peak systolic velocity, end-diastolic velocity, resistive index and pulsatility index) values of the two groups at the beginning of the study did not show any statistically significant difference. Both the right and the left central retinal artery pulsatility index (PI) values of the study group, who received HRT at the end of the third and sixth months, showed a statistically significant decline (paired-samples test, P < 0.05), while the decrease in the resistive indexes was not significant.

Conclusion: These results suggest that 6 months of combined hormone replacement therapy with estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg improves ocular vascular Doppler indices which may be a reflection of cerebral vascular status.     

Development of nocturia in relation to health, age and the menopause

Objectives:To analyse the relationship between nocturia, age, the menopausal transition, parturition and hormone replacement treatment (HRT) in women.Material and methods:A questionnaire study was carried out in 3669 randomly selected women (out of 6000 invited) in the County of Jämtland, Sweden. Questions were asked about health, the occurrence of somatic diseases and symptoms, habits, health care and medication.Results:In univariate analyses age, menopausal state and HRT, but not parturition, were associated with increased nocturia. In a multiple logistic regression analysis, independent correlates for two or more nocturnal micturition episodes versus no more than one episode were: health, poor versus good 2.9 (2.1–3.8); <5 years after the menopause versus before 1.8 (1.3–2.5); 5–9 years after the menopause versus before 2.1 (1.5–3.0); ≥10 years after the menopause versus before 3.1 (2.3–4.2). Age and HRT were deleted by the logistic regression model.Conclusion:The present data indicate that menopausal state, but not age, parturition and HRT are independent correlates of nocturia in 40–64-year-old women.     

Laboratory and Ambulatory Monitoring of Menopausal Hot Flashes

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.     

Lack of functional estrogen receptor beta influences anxiety behavior and serotonin content in female mice

Estrogen has been linked to the modulation of anxiety in females. Here we report results of anxiety tests conducted in female estrogen receptor beta (ERbeta) knockout (ERbetaKO) and wild-type (WT) mice. Ovariectomized (OVX) mice treated with chronic estradiol (E2) replacement did not behave differently on the elevated plus-maze when compared with OVX mice that did not experience hormone replacement. However, a genotype difference was noted; WT females were more likely to explore the distal portion of the open arm of the maze than ERbetaKO littermates. In addition, ERbetaKO female mice had significantly lower serotonin (5-HT) content than WT littermates in several brain regions including: the bed nucleus of the stria terminalis, preoptic area, and hippocampus. A similar trend was noted in the dorsal raphe nucleus. Dopamine content was reduced within the caudate putamen in ERbetaKO mice as compared to brains from WT animals. Thus, in the absence of functional ERbeta, regardless of the presence or absence of circulating E2 in plasma, female mice exhibited enhanced anxiety and decreased concentrations of 5-HT or dopamine in several brain regions. We hypothesize that ERbeta is required during development to modulate the effects of estrogen on anxiety and catecholamine concentrations in female mouse brains.