La Edad Crítica de la Mujer

MATURITAS Vol.26

Enero, 1997

S Punyahotra, L Dennerstein, P Lehert. Menopausal experiences of Thai women. 1: Symptoms and their correlates. Maturitas 26: 1 (JAN 1997): 1-7

S Punyahotra, L Dennerstein. Menopausal experiences of Thai women. 2: The cultural context. Maturitas 26: 1 (JAN 1997): 9-14

• This paper describes the cultural context of middle- aged Thai women who took part in a survey of symptoms and attitudes to menopause. The women lived in Nonthaburi province, adjacent to Bangkok, which has undergone a transition from rural to urban. Household structure often includes three generations. There have been changing opportunities for women in areas of education, occupation and family size and women's power increases with age. Thai women perceive menstruation as an indicator of health and take special care during menstruation. There is a special idiom in Thai 'leod cha pal - lom cha ma' (the blood will go - the wind will come) used to describe changes in a woman's behaviour, emotions and well-being during the menopause. These changes are expected to happen occasionally, not in every woman. Some women looked forward to menopause, while others were found to be ambivalent towards it.

J Nathorstboos, M Hammar. Effect on sexual life - A comparison between tibolone and a continous estradiol-norethisterone acetate regimen. Maturitas 26: 1 (JAN 1997): 15-20

• Objectives: to compare the effects of tibolone 2.5 mg (Livial(R)) with those of 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (Kliogest(R)) on sexual rife. Methods: in a 48 week, double blind, multicenter study, 437 postmenopausal women were randomised to treatment with either tibolone or 17 beta-estradiol 2 mg plus norethisterone acetate. Treatment groups were compared with respect to different aspects of sexual life with a questionnaire covering sexual experience and responsiveness during the last 30 days. Results: a total of 315 subjects completed 48 weeks treatment. In the E2/NETA group an improvement after 48 weeks compared to baseline was observed in five out of seven items assessing sexual life. In the tibolone group an improvement regarding all seven items assessing sexual life was seen. When tibolone was compared to E2/NETA significantly higher scores were found for the items assessing 'frequency', 'satisfaction' and 'enjoyment'. Conclusions: this study indicate that tibolone and E2/NETA -which both have an androgenic profile-affect several aspects of sexual life positively. The difference with respect to satisfaction with sexual enjoyment and frequency could be of clinical importance.

DJ Torgerson, RE Thomas, MK Campbell, DM Reid. Alcohol consumption and age of maternal menopause are associated with menopause onset. Maturitas 26: 1 (JAN 1997): 21-25

• Objectives: To examine whether a number of nutritional and familial factors were associated with menopausal development. Methods: A prospective postal survey amongst a random sample of 1227 women aged 47 to 51 who were premenopausal in a cross- sectional survey 2 years previously. Women were classed into three groups. premenopause (regular menstruation); irregular menstruation; postmenopausal (absence of menstrual cycle for at least 6 months). Proportional odds regression was used to identify those factors which were independently predictive of subsequent menopausal development. Results: There was an 80% (n = 983) survey response rate. After exclusion of current HRT users (n = 178), 150 (19%) women were postmenopausal, 277 (34%) had erratic menstruation and 378 (47%) were premenopause. There were significant univariate associations between menopausal status and age (P < 0.001), age of maternal menopause (P = 0.006), alcohol consumption (P = 0.005) and social class (P = 0.03). Maternal age and alcohol consumption were significantly correlated with estradiol levels (r = 0.45, P = 0.02, and r = 0.61, P = 0.02 for maternal age and alcohol consumption, respectively). In proportional odds regression analysis, age, maternal menopausal age, alcohol consumption and smoking were independently associated with menopausal status. Conclusions: These results suggest that, (1) there is a strong familial association in menopausal age, and (2) moderate consumption of alcohol is associated with delayed menopausal development.

HA Nash, V Brache, F Alvarez-Sanchez, TM Jackanicz, TM Harmon. Estradiol delivery by vaginal rings: Potential for hormone replacement therapy. Maturitas 26: 1 (JAN 1997); 27-33

• Objectives: To determine if delivery of estradiol from elastomeric vaginal rings gives estradiol blood levels in the range associated with effective estrogen replacement therapy and to determine the relation between in vitro estradiol release from the rings and blood levels in vivo. Secondary objectives related to changes in lipoprotein cholesterol, changes in climacteric symptoms, and evaluation of acceptability to users. Methods: Three ring Variants releasing approximately 100, 150 and 200 mu g/day of estradiol in vitro were used through 22 days in 21 postmenopausal women, 7 on each dose level. Blood samples for measurement of estradiol were taken at 3-4 day intervals. Lipoprotein cholesterol was measured before and at the end of treatment. Women were questioned about climacteric symptoms and about their satisfaction with the ring. Results: Mean serum estradiol levels for the three groups of rings were 63 +/- 6, 94 +/- 5 and 136 +/- 13 pg/ml for the 100, 150 and 200 mu g/day rings, respectively. FSH levels declined during ring use and the maturation values of cells collected on vaginal swabs markedly increased. Total and LDL cholesterol were significantly reduced and HDL cholesterol was not significantly changed. All women reported relief of post- menopausal symptoms. Vaginal discomfort during the first 3 days of use was reported by 12 women but overall satisfaction with the method was high. Conclusions: Women using the vaginal rings attained estradiol blood levels compatible with control of climacteric symptoms and bone loss. The relation between in vitro estradiol release and blood levels in vivo was essentially identical for all 3 doses. The use of vaginal rings to deliver estradiol for hormone replacement therapy is judged to merit further evaluation.

MJ Garton, C Cooper, D Reid. Perimenopausal bone density screening - Will it help prevent osteoporosis? Maturitas 26: 1 (JAN 1997): 35-43

• Objective. To estimate the potential efficacy and cost-effectiveness of hormone replacement therapy (HRT) in the prevention of osteoporotic fractures, with and without the assistance of perimenopausal bone mineral density (BMD) screening. Method: Residual lifetime fracture experience of a hypothetical cohort of 100000 British women aged 45 years at baseline, modelled using prevailing UK mortality and fracture rates. Appropriate fracture risk gradients were used to estimate the distribution of future fragility fractures (distal forearm, proximal femur and clinically diagnosed vertebral fractures) according to quarters of baseline bone density measured at fracture specific sites. We assumed that 72% of the population could be contacted and would attend for HRT counselling, with or without bone densitometry, that IO years of continuous HRT use would reduce fracture rates by 50%, and that compliance with HRT might vary between 10% and 50%. Universal recommendation of HRT was compared to selective treatment protocols offering HRT to those women whose BMD fell below the 25th, 50th or 75th percentile of BMD at the lumbar spine, femoral neck or distal forearm, measured either singly or in combination. Results: The proportion of future fractures averted was closely related to compliance with therapy, but for any given level of compliance, universal treatment always achieved the greatest reduction in fractures. If compliance was 10%, universal HRT was also the most cost-effective strategy, but if compliance was higher or if the unit cost of HRT increased, selective strategies were often more cost-effective. The sensitivity of BMD screening in identifying women at risk of future fracture could be increased by relaxing the BMD decision threshold, or expanding the number of skeletal sites measured, or both. However increments in test sensitivity were always accompanied by reductions in specificity. Conclusions: If BMD measurement does not influence compliance, then universal treatment with HRT is likely to prevent more fractures, at a similar or lower average cost per fracture averted, than selective therapy. However, if BMD screening leads to increased compliance, or if more expensive forms of treatment were used, then our model suggests a favourable impact of screening on the numbers and/or net cost of fractures prevented.

HHV Goh, SS Ratnam. Effects of hormone deficiency, androgen therapy and calcium supplementation on bone mineral density in female transsexuals. Maturitas 26: 1 (JAN 1997): 45-52

• A total of 79 healthy female transsexuals, divided into four groups, were involved in this study. Group 1 comprised 15 pre-operated normal cycling females; Group 2, five pre-operated females who were on regular androgen therapy for 1-3 years; Group 3, 27 post-operated females who were on regular androgen therapy for 2-12 years and Group 4, 32 post-operated females who either had stopped or were on irregular androgen therapy. A bone scan of the lumber spine, at positions L2-L4, was carried out for each subject. A blood sample was taken for measurement of plasma testosterone concentrations. Ten subjects from Group 3 had a repeat bone scan following 10-39 months of calcium supplement (625 mg daily as calcium carbonate); another 10 post- operated females of Group 3 had a repeat bone scan 6-59 months later; and five subjects from Group 4 had a repeat scan following resumption of regular androgen therapy for 17-27 months. The mean +/- SE concentrations of testosterone of Groups 1-4 were, respectively, 0.58 +/- 0.05, 10.1 +/- 2.48, 7.7 +/- 0.98 and 0.99 +/- 0.14 ng/ml. Pre-operated females (Group 2) following 1-3 years of regular androgen therapy had significantly higher BMD and age- matched BMD than corresponding levels in pre- operated normal cycling females in Group 1. While the age-matched BMDs of post-operated females, who were on regular androgen therapy, were not significantly different, the mean BMD was significantly lower than corresponding values in the controls of Group 1. Post-operated females in Group 4 had significantly lower BMDs and age- matched BMDs as compared to corresponding values in controls of Group 1. The BMDs and age-matched BMDs of post-operated females, who were on regular androgen therapy, were significantly raised following daily calcium supplementation for durations ranging from 10-39 months. A repeat bone scan carried out following a lapse of 6-59 months did not reveal any significant change in the BMDs and age-matched BMDs of 10 post-operated females on regular androgen therapy. On the other hand, the BMDs and age-matched BMDs of post-operated females in Group 4 were significantly raised following the resumption of regular androgen therapy for 17-27 months. Results of the present study showed that ovariectomy and remaining in the hormone-deficient state for a sufficiently long duration was associated with a definite loss of bone mass. However, it was shown in this study that the resumption of regular androgen therapy for a sufficient duration could arrest this loss and, additionally, substantially increase the bone mass. Androgen appears to have a potentially greater impact on bone mass than oestrogen. Furthermore, calcium supplementation in a Singaporean population, which is accustomed to a low dietary calcium intake, can assist in the accretion of a higher bone mass in an adult population.

TK Lau, TKH Chung, CJ Haines. A preliminary study on the effect of hormone replacement therapy on peripheral flow velocity in postmenopausal women. Maturitas 26: 1 (JAN 1997):53-56

• Apart from predisposing to the formation of atherosclerosis in the coronary and cerebrovascular circulation, the menopause is also associated with an increased risk of developing peripheral vascular disease. The aim of this observational study was to determine whether the administration of hormone replacement therapy (HRT) had any effect on peripheral flow velocity in postmenopausal women. Changes in peripheral resistance were recorded in 11 healthy postmenopausal women using Doppler ultrasound. The pulsatility index (PI) of the brachial, radial, dorsalis pedis and popliteal arteries was measured before treatment and every 2 months after the commencement of HRT for 6 months. There was a significant decrease in the PI of the radial and dorsalis pedis arteries after HRT, and there were also reductions in the PI of the brachial and popliteal arteries which were not statistically significant. These changes persisted over the complete study period. Our findings suggest that the administration of HRT will have a beneficial effect on peripheral flow velocity in postmenopausal woman. These changes require confirmation in a larger controlled trial.

D Botsis, D Kassanos, D Kalogirou, G Antoniou, N Vitoratos, P Karakitsos. Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: A comparison. Maturitas 26: 1 (JAN 1997): 57-62

• Objective: The objective of this study was to compare the efficacy of locally administered low- dose estrogens (0.625 mg of conjugated estrogens) and orally administered tibolone in postmenopausal women with symptoms and signs of atrophic vaginitis. Vaginal ultrasound was performed for the evaluation of endometrial or ovarian abnormalities. Methods: A 6-month comparative randomised prospective study of women taking tibolone and locally administered low-dose estrogens. Seventy two postmenopausal women with symptoms of atrophic vaginitis were examined with vaginal ultrasound. The endometrial thickness, the endometrial volume, the uterus and the ovaries were measured before and after 6 months of treatment with low-dose estrogens or tibolone. Results: In group A (low-dose estrogens treatment) the mean endometrial thickness, before and after treatment, was 3.0 +/- 0.1 mm and 2.9 +/- 0.8 mm, respectively The mean ovarian volume was 3.9 ml. There were no changes in uterine volume during the treatment period. In group B (treated with tibolone) endometrial thickness was 3.2 +/- 0.3 mm and 3.2 +/- 0.7 mm, respectively. One women experienced vaginal bleeding. The volume of corpus uteri was unchanged after treatment. The volume of both ovaries was 4.2 ml and 3.9 ml, respectively. The overall acceptability of both types of administration was good. Conclusions: This study, using vaginal ultrasound, has shown that either hormone replacement therapy with tibolone or symptomatic treatment with low-dose estrogens, gives no sign of endometrial proliferation measured as endometrial thickness.

SX Zheng, Y Vrindts, M Lopez, D Degroote, PF Zangerle, J Collette, N Franchimont, V Geenen, A Albert, JY Reginster. Increase in cytokine production (IL-1 beta, IL-6, TNF- alpha but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26: 1 (JAN 1997): 63-71

• Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Several investigations have suggested that ne of the mechanisms through which estrogen prevents bone loss was a modulation on secretion or release of Various cytokines that are known to influence bone remodeling, even if some recent data have challenged this hypothesis. However, in established osteoporosis, the possibility that enhanced cytokines activity may account for the progression of this disease remains unclear and controversial. We sought here to determine whether production of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct stimulation in whole blood, was different in healthy (n = 30) or osteoporotic postmenopausal women (n = 24) and whether lumbar bone density (1-BMD) correlated with the Values of cytokine production observed in these conditions. A significant difference was observed between the osteoporotic and control subjects for IL-IP (p < 0.0001), IL-6 (p < 0.001) and TNF-alpha (p = 0.027) productions, the values being higher in the osteoporotic women. No significant differences between the groups were observed for IFN-gamma (p = 0.51), GM-CSF (p = 0.70) or LIF (p = 0.97). In the whole population, statistically significant negative correlations were observed between lumbar BMD and IL-1 beta (r = -0.46) (p < 0.0005), IL-6 (r = -0.50) (p < 0.0001) and TNF-alpha (r = -0.39) (p < 0.005) production while no such correlations were observed for IFN-gamma, GM-CSF or LIF. In conclusion, the study of cytokine production by immune cells cultured in autologous whole blood suggests that in women more than 10 years past the menopause and presenting a decrease in lumbar bone density corresponding to the new WHO definition of 'osteoporosis', production of IL-1 beta, IL-6 and TNF-alpha is still increased compared to controls matched for age and ovarian function, while no differences are reported for IFN-gamma, GM-CSF or LIF production.

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