Olfactometric and rhinomanometric outcomes in post-menopausal women treated with hormone therapy: a prospective study

Sir, Caruso and his co-workers in their paper (Caruso et al., 2004)report a favourable effect of hormone replacement therapy (HRT)on olfactory sensitivity in 46 naturally post-menopausal womenrequiring HRT treatment for climacteric symptoms; moreover,they have demonstrated that both combined and sequential continuousHRT ‘increase significantly nasal airflow, indirectlycausing a decrease     

Olfactometric and rhinomanometric outcomes in post-menopausal women treated with hormone therapy: a prospective study

BACKGROUND: The aim of this prospective study was to evaluate the effects of hormone therapy (HT) on olfactory sensitivity in post-menopausal women. METHODS: Forty-six naturally post-menopausal women underwent rhinomanometric and olfactometric measurements to compare nasal airflow resistance values and olfactometric thresholds during the eighth month of HT treatment with baseline levels prior to starting HT. Eighteen women used an oral HT regimen, and twenty-eight women used transdermal patch HT. RESULTS: Rhinomanometric values during HT were statistically differ from those at baseline (P < 0.001). Olfactometric threshold data indicated a higher sensitivity during the HT treatment than at baseline (P < 0.001). Finally, no statistically significant difference was observed among women using oral or patch HT administration on rhinomanometric and olfactometric values. CONCLUSIONS: Our study demonstrates that 8 months of treatment with estrogen and progestogens in HT preparations has an effect on nasal airflow resistance and the olfactory thresholds to odours. We believe that estrogens could influence neuronal plasticity, and the neuronal conduction time into the olfactory system. Our findings confirm that gonadal steroids such as estrogen have an influence on non-genital targets; this relationship might have a beneficial impact on sensorineural communication and emotional behaviour.     

Responses in post-menopausal women: Counselling post-menopausal women for donor in-vitro fertilization and hormone replacement therapy

Oocyte donation was applied initially to women with hypergonadotrophichypogonadism or ‘premature menopause’. Later, therapywas extended to recipients >40 years old and to post-menopausalwomen. In all cases, enhanced implantation and pregnancy rateswere obtained by many investigators. Post-menopausal women mustbe informed about in-vitro fertilization results, obstetricrisks for themselves and their newborn babies. They must bescreened and investigated as accurately as possible for anyexisting medical contraindication. Results are encouraging becausethese patients become pregnant as easily as young donors, withpregnancy rates of 58, 34.6 and 37.9% per patient, per synchronizationcycle and per transfer respectively. Abortion rates (5%) arevery low considering the women are >45 years old. The post-menopausaluterus can sustain implantation, grow and carry pregnancy toterm and reduce adequately after labour. The incidence of maternalmorbidity during pregnancy is less encouraging. A higher incidenceof pregnancy-related diseases, e.g. gestational diabetes, hypertension,moderate and severe pre-eclampsia have been reported.     

Micturition complaints in postmenopausal women treated with continuously combined hormone replacement therapy: a prospective study

OBJECTIVES: To study parameters of the micturition pattern in postmenopausal women and the effect of an oral continuously combined HRT-regimen. METHODS: Hormone therapy consisted of 2 mg 17 beta-oestradiol in combination with either 2.5, 5, 10 or 15 mg dydrogesterone, orally once a day. The baseline assessment was done just before starting hormone replacement therapy, the second assessment took place after 6 months of hormone therapy. Data were collected using a standardized questionnaire and focused on diurnal urinary frequency, nocturnal urinary frequency and urinary incontinence as parameters of the micturition pattern. Furthermore, bacteriuria was assessed. RESULTS: One hundred and two women entered the study and 95 women completed 6 months of hormone replacement therapy. Urinary incontinence was reported by 44.1% of the women, in 19.6% of the women it occurred more than twice a week. Both diurnal frequency and nocturnal frequency was reported by 28.4% of the women. For women with frequency or nocturia, the number of voids significantly decreased after 6 months hormone replacement therapy. Nocturia disappeared in 65.4% of the women after treatment and 23.3% reported to be cured of their urinary incontinence. Bacteriuria was present in the same seven women before and after hormone treatment. Dydrogesterone dose did not influence treatment outcomes. CONCLUSIONS: Postmenopausal women report improvement on urinary incontinence and nocturia after 6 months of a continuously combined hormone replacement therapy regimen. The improvement was most outspoken with regard to nocturia. Bacteriuria was not influenced. Different doses of dydrogesterone did not effect these findings.     

A prospective study evidencing rhinomanometric and olfactometric outcomes in women taking oral contraceptives.

BACKGROUND: The aim of this prospective study was to evaluate the changes in olfactory sensitivity of oral contraceptive (pill) users. METHODS: Sixty women underwent rhinomanometric and olfactometric determinations during the follicular, periovular and luteal phases of the menstrual cycle, and at day 7, 14 and 21 of contraceptive intake. Thirty-one women used 30 microg ethinyl oestradiol plus 75 microg gestodene and 29 women used 20 microg ethinyl oestradiol plus 150 microg desogestrel. RESULTS: Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases. Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle. The rhinomanometric surveys in pill users were statistically different from those of the luteal phase (P < 0.02) and the follicular and periovular phases (P < 0.001). The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances, and from those of the periovular phase for each odorous substance, but similar to those of the luteal phase (P = NS). CONCLUSIONS: Unlike the rhinomanometric airflow and trans-nasal pressure, the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.     

Dry eye in post-menopausal women using hormone replacement therapy

PURPOSE: To evaluate the effect of hormone replacement therapy (HRT) on dry eye in post-menopausal women. METHODS: Forty post-menopausal women with dry eye (20 patients, group 1) and without dry eye (20 patients, group 2), and planning to receive HRT (estrogen plus progesterone), were recruited as the study groups. Forty age-matched untreated women were enrolled as controls (group 3 with dry eye, 5 patients; group 4 without dry eye, 35 patients). Patients having at least one of the symptoms (dryness, itching, photophobia, foreign body sensation, and tearing) together with two of the tests with positive results for dry eye (tear film break-up time (BUT), fluorescein staining of the cornea, analysis of the meibomian gland, and Schirmer I test) in both eyes were considered dry eye positive. Hormonal assay for follicle stimulating hormone, luteinizing hormone, estradiol, and free testosterone was performed. Dry eye statuses in the groups were evaluated statistically. RESULTS: Four patients with incomplete follow-up data were excluded. HRT use increased estradiol levels in the groups. Mean ages of patients (50.2+/-4.8 and 50.7+/-3.9 years, and 50.0+/-4.6 and 53.0+/-3.9 years) were similar (p=0.67). Duration of menopause in groups 1 and 2 (3.2+/-2.2 and 1.4+/-1.2 years; p=0.01), and in groups 3 and 4 (3.0+/-1.6 and 1.7+/-1.3 years; p=0.014) were different. At the third month examinations, all of the patients in group 1, and 11 patients (61.1%) in group 2 had dry eye (p=0.003). CONCLUSION: Duration of menopause and use of HRT may increase the incidence of dry eye in post-menopausal woman.     

Changes in body composition during post-menopausal hormone therapy: a 2 year prospective study

BACKGROUND: Post-menopausal hormone therapy (pHT) induces changes in both body composition and bone mineral density (BMD). METHODS: In 109 post-menopausal women beginning either tibolone 2.5 mg (n=29), tibolone 1.25 mg (n=42) or estradiol 2 mg plus norethisterone acetate 1 mg (E2 + NETA) (n=38), we assessed body composition, total and regional BMD by dual energy X-ray absorptiometry, and the serum bone alkaline phosphatase (BAP), osteocalcin and the urinary excretion to type I collagen C-telopeptide (CTX) at baseline and after 2 years. RESULTS: At baseline, BMD at all sites correlated negatively with age and years since menopause, and positively with lean mass and fat mass (r=0.42, P<0.001 and r=0.26, P=0.006 at the total femur). During treatment, BMD increased at all sites (P<0.001), and serum BAP, osteocalcin, and urinary CTX decreased in all groups (P<0.001). Lean mass increased whereas android fat and android obesity index decreased. The increase in BMD at all sites correlated positively with changes of lean mass at 2 years. CONCLUSIONS: Both fat mass and lean mass are related to BMD in post-menopausal women, the relationship being strongest with lean mass; an increase in lean mass and a change in distribution of body fat are observed during treatment with E2 + NETA and tibolone.     

Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis

BACKGROUND: Long-term post-menopausal hormone therapy (pHT) was often regarded as first-line therapy to prevent fractures in post-menopausal women, a recommendation under scrutiny given the benefit-risk profile of the Women's Health Initiative results of the estrogen-progestin combination. Apart from controlled clinical studies providing data with fractures as an end point, measures of lumbar and hip bone mineral density (BMD) may be used to assess bone-related effects of pHT. The objective of this study was to conduct a systematic review of 2-year trials, published between 1990 and December 2002, and assessing changes in BMD by any estrogen including ethinyl estradiol, any estrogen plus any progestin, or tibolone. METHODS: We searched MEDLINE, EMBASE and systematic reviews. Thirty-nine randomized, prospective, controlled 2-year trials were analysed in pre-specified groups according to the profile of the compounds. RESULTS: Virtually all pHT regimens at least maintain BMD at the lumbar spine and the hip compared with baseline; there is no apparent difference between the various estrogenic compounds. Tibolone, a synthetic progestin, appears to be as effective as any estrogen. Most trials were conducted in early post-menopausal women, fewer in women with hysterectomy and/or bilateral oophorectomy. CONCLUSIONS: The size of impact on BMD does not appear to differ between tibolone and any estrogen compound studied.     

Auditory brainstem response in postmenopausal women treated with hormone replacement therapy: a pilot study

OBJECTIVE: To research the nongenital audiological target for gonadal steroids in postmenopausal women who are treated with hormone replacement therapy. DESIGN: Fifty postmenopausal volunteers were treated with hormone replacement therapy. Women with an intact uterus had sequential weekly transdermal estradiol plus nomegestrole acetate 5 mg orally for 12 days per month or a continuous daily oral dose of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg tablet. Eighteen surgically postmenopausal women received a weekly transdermal estradiol system. Twenty-five postmenopausal volunteers-5 with a natural menopause and 10 with a surgical menopause-and 20 premenopausal normally cycling women were used as a control group. Each woman performed auditory brainstem response by auditory-evoked potentials for waves I, III, and V and for interpeak I-III, I-V, and III-V intervals. RESULTS: Women who were treated with hormone replacement therapy showed wave latencies and interpeak latencies shorter than those for postmenopausal women in the control group (p < or = 0.05), overlapping those of the premenopausal women (p > 0.05). Women who were treated with estrogen replacement therapy showed shorter time latencies than those treated with combined hormone replacement therapy (p < or = 0.05). CONCLUSIONS: Our data suggest that fluctuating hormone levels cause changes in auditory brain-stem response waves, even if the exact mechanism of activity of the gonadal steroids is not clear. However, we believe that estrogen may influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiological system.     

Carotid artery wall thickness in women treated with hormone replacement therapy

Objective: To measure the thickness of the individual layers (externa, media, intima) of the carotid artery in two groups of postmenopausal women. Methods: A high resolution ultrasound (25-MHz Osteoson DIII Minhorst) was used to assess the distal end of the common carotid artery. Forty-six women were on hormone replacement therapy (Premarin 0.625 mg nad Norgestrel 1 mg) for more than 1 year. The measurements of the treated group were compared to those of 51 postmenopausal women who acted as controls. Results: No significant difference between the externa and media layers of both groups of women were noted. The media showed a tendency to be thicker in the treated group. The intima of the untreated group was found to be significantly thicker than that of the treated group (P < 0.05). Significant correlations were found between the layers of the carotid artery especially between the externa and media both mainly composed of connective tissue (Collagen Type I and III and elastin). The media/intima ratio of the treated women was significantly higher than that of the untreated group (P < 0.003). Conclusion: It is postulated that the changes observed may be due to the effect of oestrogen on connective tissue. These arterial changes induced by hormone replacement therapy may partially explain the cardioprotective effect this treatment has on postmenopausal women. The increased intimal thickness in untreated women compared to treated ones on the other hand would represent the reduction in atheromatous plaque formation in women on oestrogen replacement therapy.     

Skinfold thickness and long-term post-menopausal hormone therapy

Skinfold thickness was measured in 130 post-menopausal women treated with long-term hormone therapy. One group of 50 women took oestradiol valerate 2 mg/day for 3 wk out of 7, a second group comprising 19 women received oestriol succinate 2 mg/day and the remaining group of 61 women used oestradiol valerate 2 mg/day combined sequentially with norgestrel 0.5 mg/day. The duration of treatment in these groups was 6.3 ± 0.4, 6.4 ± 0.4 and 3.3 ± 0.3 yr, respectively. The control group was made up of a further 89 post-menopausal women. The skinfold thickness in all the treated groups was significantly greater than that in the controls.     

No increase in C-reactive protein levels during intranasal compared to oral hormone therapy in healthy post-menopausal women

BACKGROUND: Inflammation plays an important role in the development of atherosclerotic disease. Oral post-menopausal hormone therapy increases serum C-reactive protein (CRP) levels. This study compared the effects of intranasal and oral administration of 17beta-estradiol (E2) combined with norethisterone acetate (NETA) on markers of inflammation in healthy post-menopausal women. METHODS: Ninety healthy post-menopausal women (age 56.6 +/- 4.7 years) participated in this 1-year trial. After computerized block randomization, they daily received, in a double-blind fashion, either intranasal E2/NET [175 microg/275 microg (n = 47)] or oral E2/NETA [1 mg/0.5 mg (n = 43)]. Concentrations of high sensitivity CRP and adhesion molecules were measured at baseline and after 12, 24 and 52 weeks of treatment. RESULTS: CRP levels were increased (P = 0.001) in the oral but not in the intranasal group. The increase in the oral group was highest at week 12 (64.9%) and was larger (P < 0.01) compared with the non-significant increase (8.6%) found in the intranasal group. Both groups showed decreases (P < 0.001) in soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM) and sE-selectin. The decreases were larger (P < 0.01) in the oral than in the intranasal group. CONCLUSION: Intranasal E2/NET therapy did not significantly increase CRP levels, in contrast to the increase observed in the oral E2/NETA treatment group. Both intranasal and oral therapy lowered plasma concentrations of adhesion molecules, however, more so in the oral group.     

Reproductive history in relation to plasma hormone levels in healthy post-menopausal women

OBJECTIVES: We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer. METHODS: We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained. RESULTS: Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density. CONCLUSIONS: These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.     

Information needs of post-menopausal women with hormone receptor positive early-stage breast cancer considering adjuvant endocrine therapy

Objective

To identify questions that post-menopausal women with receptor-positive early-stage breast cancer want answered before their adjuvant-endocrine-therapy decision is made.

Methods

We surveyed patients eligible for adjuvant-endocrine therapy in the previous 3–18 months. Participants rated the importance of getting each of 95 questions answered before the decision is made (options: essential/desired/not important or no opinion/avoid). For each question rated “essential”/“desired”, the participant also identified the purpose(s) for the answer: to help her understand, decide, plan, or other reason(s).

Results

The response rate was 55% (188/343). Participants rated a mean of 57 (range: 1–95) questions “essential”, 80 (range: 1–95) “essential” or “desired”, and 2 (range: 0–27) “avoid”. Every question was “essential” to ≥31% of participants, and “essential”/“desired” to ≥63%. All but eleven questions were rated as “avoid” by ≥1 participant. The most frequent purposes for “essential” questions were to: understand their situations (mean 45, range: 0–95), decide (mean 18, range: 0–94), and plan (mean 13, range: 0–95).

Conclusion

Many patients want a lot of information before this decision is made but there is wide variation within the group in both the number and in which questions they want answered.

Practice implications

Patient education in this setting needs to be tailored to the needs of the individual patient.     

Effect of HRT on hormone responses to resistance exercise in post-menopausal women

Purpose: The purpose of this study was to evaluate the effect of hormone replacement therapy (HRT) on the acute and chronic hormonal responses to resistance exercise in post-menopausal women. Methods: Thirty-two post-menopausal women were recruited for this study; 16 who were currently using HRT and 16 who were not using HRT. Subjects in both the HRT and NHRT groups were randomly assigned to either a resistance training group (N=16; 8 HRT and 8 NHRT) or a control group (N=16; 8 HRT and 8 NHRT). The training group completed a supervised resistance training program three times a week for 12 weeks. To evaluate changes in hormone levels, resting blood samples were drawn at weeks 0, 4, and 13 of the program. In addition, at weeks 0 and 13, post-exercise blood samples were drawn in order to examine the hormone response to an acute bout of resistance exercise. Samples were analyzed for serum growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisol. Results: There were no significant changes in resting hormone levels between weeks 0, 4, and 13 of the training program. There was a significant week-by-group interaction for DHEA (P<0.05) and cortisol (P<0.05) with the NHRT-training group having a greater post-exercise increase in DHEA and cortisol after training. Overall, the post-exercise GH levels were significantly greater than pre-exercise (P<0.05) or recovery levels (P<0.01). There were no significant differences between HRT and NHRT groups in the acute hormone response to exercise. Conclusion: These results indicate that HRT will not have an effect on the acute or chronic hormone response to a recreational resistance training program in post-menopausal women.     

The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis

We reviewed epidemiological and experimental studies of female gonadal hormone replacement therapy (HRT) on cognitive function in post-menopausal women and carried out meta-analyses. In healthy ageing women, HRT has small and inconsistent effects that include enhancement of verbal memory, abstract reasoning and information processing. Epidemiological studies show larger effects than experimental studies, which is not related to sample size. Important confounds may be that women who start using HRT are healthier than women who do not. Also, controlling for socio-economic status diminishes the effect of HRT. The effects of HRT may depend on the age and type of menopause and the therapeutic intervention used, with the most widely used drug, Premarin, having least effect. However, the effects are independent of mood and climacteric symptom alleviation. There is a paucity of experimental studies that include healthy elderly women. The evidence for an estrogen deficiency in women with dementia and cognitive dysfunction is inconsistent. Nevertheless, epidemiological studies suggest that HRT protects against the development of clinically diagnosed Alzheimer's disease. However, poor recall of HRT use by patients and altered physician behaviour may have confounded the effects. Surprisingly, both healthy and demented women with low education seem to benefit most from HRT. Three recent controlled experimental studies using Premarin showed no effects of HRT in preventing further cognitive decline in women who already have Alzheimer's disease. Duration of treatment seems to play an important role, with beneficial effects declining-and even reversing-with longer treatment in women with Alzheimer's disease.Future research should further investigate the cognitive effect of different HRT preparations, serum estrogen levels, and the interactions of HRT with age, menopausal status and existing protective (e.g. education) and risk factors (e.g. smoking and apolipoprotein E genotype) for cognitive decline and Alzheimer's disease.     

Intervertebral disc height in treated and untreated overweight post-menopausal women

BACKGROUND: The effect of the menopause and HRT on the intervertebral discs has not been investigated. METHODS: One hundred women were recruited, comprising of 44 post-menopausal women on HRT, 33 untreated post-menopausal women and 23 pre-menopausal women. The height of the intervertebral discs between the 12th thoracic vertebra and the 3rd lumbar vertebra was measured by utilizing the bone densitometer height cursors. RESULTS: The untreated menopausal group of women had the lowest total disc height (D1-D3: 1.95 0.31 cm). This was significantly lower than the pre-menopausal group D1-D3: 2.16 0.24 cm) and the hormone-treated group (2.2 0.26 cm) (P > 0.02). The 2nd intervertebral disc consistently maintained a significant difference between the untreated menopausal group (D2: 0.63 0.13) and the other two groups (pre-menopausal group (D2: 0.72 0.09 cm) and treated menopausal group (D2: 0.73 0.12 cm) (P > 0.02). CONCLUSIONS: Estrogen-replete women appear to maintain higher intervertebral discs compared to untreated post-menopausal women. The estrogenic milieu may be relevant because of the significant impact it has on the hydrophilic glycosaminoglycans, the water content, collagen and elastin of the intervertebral discs. The maintenance of adequate disc height may allow the intervertebral discs to retain their discoid shape and viscoelastic function, containing vertical forces which may threaten spinal architecture leading to vertebral body compression fractures.     

Myocardial infarction and estrogen therapy in post-menopausal women.

Data obtained from two multipurpose surveys of hospitalized patients were examined to determine the risk of nonfatal acute myocardial infarction in post-menopausal women 40 to 75 years of age in relation to use of estrogen-containing drugs. Eight (2.4 per cent) of 336 myocardial infarction patients and 330 (4.9 per cent) of 6730 reference patients were regular estrogen users (crude rate ratio, 0.47) at the time of hospitalization. After control for confounding variables -- among them, age, past history of myocardial in farction, angina, diabetes, and hypertension (alone or in combination) and cigarette smoking -- the summary point estimate of rate ratio was 0.97 with 95 per cent confidence limits of 0.48 and 1.95. Thus, there was no evidence of a statistically significant association between current regular use of estrogens and nonfatal acute myocardial infarction.     

Sex steroid replacement in post-menopausal women: effects on thyroid hormone status

We have measured serum thyroxine (T4), triidothyronine (T3), thyroid-stimulating hormone (TSH) free thyroxine (FT4) and thyroxine-binding globulin (TBG) levels in a total of 5 post-menopausal women who were receiving oestrogen alone (Premarin, n = 19), progestogen alone (Primolut-N, n = 12), a combination of oestrogen and progestogen (Prempak C, n = 14) or no treatment (control group, n = 12). No differences were observed between the Premarin and Prempak C groups; both exhibited elevated T4 and TBG levels, although free thyroxin (FT4) and T4/TBG concentrations were normal relative to those in the control group. The Primolut-N subjects showed subnormal T3 and FT4 levels relative to the controls. It was concluded that it is not possible to make general statements regarding the effects of sex steroids on FT4 levels.     

Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy.

Doppler ultrasound was used to investigate circadian variations in uterine artery blood flow in 20 post-menopausal women in the oestrogen-only phase of combined oestrogen hormone replacement therapy with cyclical oral norethisterone or dydrogesterone. All women were examined between 0800 and 0830 h and then again between 1800 and 1830 h on the same day. Mean arterial blood pressure, heart rate and a blood sample for measurement of serum oestradiol were taken at each visit. Indices of uterine artery blood flow included the pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity. No significant differences in the mean arterial blood pressure, pulse rate and oestradiol concentrations were detected between morning and evening visits. Significant fluctuation was observed in the pulsatility index (P < 0. 001), resistance index (P < 0.001) and time-averaged maximum velocity (P < 0.01). The assessment of uterine artery blood flow in post-menopausal women should take into account the presence of circadian variations to ensure accuracy and reproducibility of Doppler investigations.