Transdermal Estrogen Replacement Therapy Research Articles

Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors

The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown. To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors. Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 μg/24h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured. No difference between groups was found for change in plasma HDL-C (p=0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus+5.8 (-6.3,+16.9)% placebo group, p=0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus+7.4 (-1.5,+18.1)% placebo group, p=0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p<0.0001) and insulin resistance (p=0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (β=-0.26, p=0.004). Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.

Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls-A Longitudinal Study.

Estrogen replacement therapy (ERT) for Turner syndrome (TS) is a widely discussed topic; however, the optimal model of ERT for patients with delayed diagnosis and/or initiation of therapy is still unclear, mainly due to insufficient data. We present the results of a prospective observational single-center study in which the efficacy of late-onset puberty induction by one-regimen transdermal ERT in TS girls was evaluated. The analysis encompassed 49 TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified transdermal ERT protocol was used for puberty induction (first two months 12.5 μg/24 h, thereafter 25.0 μg/24 h until breakthrough bleeding). Clinical visits for examination and therapy modification took place every 3-6 months. Transabdominal pelvic ultrasound examinations were performed at least twice: at the beginning and at the end of follow-up. The mean (SD) age at ERT induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years. Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4 after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier initiation of ERT (≤14 years), B2 (p = 0.059) was achieved faster and B4 (p = 0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%) patients had at least stage B3 at menarche. The karyotype, initial weight, and body mass index had no impact on puberty tempo during ERT. The uterine volume increased significantly during ERT in all the study group (p < 0.0001), and in half of the patients, the increase was at least 12.4-fold. It did not correlate with the duration of treatment (p = 0.84) or the dose of estradiol per kilogram (p = 0.78), nor did it depend on karyotype (p = 0.71) or age at ERT initiation (p = 0.28). There were no differences in ΔhSDS during ERT (p = 0.63) between the two age groups (ERT ≤14 and >14 years). The presented easy-to-use fixed-dose regimen for late-onset puberty induction allowed for a satisfactory rate of achieving subsequent puberty stages and did not influence the growth potential.

Persistency with estrogen replacement therapy among hysterectomized women after the Women’s Health Initiative study

ABSTRACTObjectives Many women are reluctant to undergo estrogen replacement therapy (ERT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of ERT in hysterectomized women over the past decade, reflecting changes in the post-Women's Health Initiative (WHI) era.Methods We analyzed 8045 patients receiving ERT from 2004 to 2013 using the Disease Analyzer database.Results After 12 months of follow-up, only 24.6% of patients receiving 1 mg and 24.5% of patients receiving 2 mg of oral ERT were still on treatment (p < 0.0001). The persistency rate of patients receiving <50 μg of transdermal ERT was 28.6% compared to 33.5% for patients receiving >50 μg within the 12 months of follow-up. ERT that began in 2007–2009 was associated with a higher discontinuation rate (hazard ratio 1.06, p = 0.0660) than ERT that began in 2010–2013 (hazard ratio 0.88, p = 0.0001).Conclusions Our results indicate low persistency rates in women on ERT irrespective of the dose as well as the route of administration. However, a decrease in discontinuation rates was found when comparing women in the early vs. late post WHI era.

Roles of Sex Steroid Hormones and Nitric Oxide in the Regulation of Sympathetic Nerve Activity in Women

HomeHypertensionVol. 61, No. 4Roles of Sex Steroid Hormones and Nitric Oxide in the Regulation of Sympathetic Nerve Activity in Women Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRoles of Sex Steroid Hormones and Nitric Oxide in the Regulation of Sympathetic Nerve Activity in Women Kazushi Tsuda Kazushi TsudaKazushi Tsuda Cardiovascular and Metabolic Research CenterKansai University of Health SciencesOsaka, Japan Search for more papers by this author Originally published4 Mar 2013https://doi.org/10.1161/HYPERTENSIONAHA.111.01075Hypertension. 2013;61:e36Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 To the Editor:We read with great interest the article by Dr Carter et al1 dealing with the relationship between ovarian cycle and sympathoexcitation in premenopausal women. The results of their study demonstrated that the mid luteal phase of the ovarian cycle was characterized by sympathoexcitation, and that the degree of sympathoexcitation might be partially dependent on the degree of sex steroid surges. The authors indicated that increases in estradiol were associated with decreases in muscle sympathetic nerve activity during the the mid luteal phase, suggesting that estradiol might be sympathoinhibitory. In addition, the strong inverse association between muscle sympathetic nerve activity and changes in estradiol/progesterone ratio was observed. The authors proposed that a dynamic interaction among estradiol, progesterone, and muscle sympathetic nerve activity may be related to the cardiovascular risk in postmenopausal women.Evidence indicates that one of the mechanisms underlying the cardiovascular protective effects of estrogen may be the enhancement of NO production. In an in vitro study presented earlier, we demonstrated that 17β-estradiol significantly improved membrane microviscosity of red blood cells through the NO-dependent mechanism in postmenopausal women.2 It was also shown that hormone replacement therapy ameliorated membrane microviscosity of red blood cells with a concomitant increase in plasma NO-metabolite levels in postmenopausal women.3 In this context, it is strongly suggested that estrogen-induced NO might have a beneficial effect on the rheological behavior and the microcirculation in postmenopausal women. Vongpatanasin et al4 have reported that transdermal estrogen replacement therapy decreased muscle sympathetic nerve activity at rest in postmenopausal women. On the contrary, it was demonstrated that acute intravenous administration of NO synthase inhibitors might increase blood pressure and activate sympathetic nerve activity,5 suggesting that NO might act as a sympathoinhibitory substance. Therefore, we would like to know whether the degree of estradiol and estradiol/progesterone ratio during the ovarian cycle might be correlated with the endothelial function, such as plasma and urinary NO-metabolite levels or flow-mediated dilatation of the brachial artery, in the study of Dr Carter et al. It would be important to assess more precisely the relationships among estrogen, progesterone, and NO, and their role in the regulation of sympathetic nerve activity during sex steroid surges.Kazushi TsudaCardiovascular and Metabolic Research CenterKansai University of Health SciencesOsaka, JapanDisclosuresNone.FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 500 words (typed double-spaced) plus 5 references in length and may be subject to editing or abridgment.

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH(2)-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

Transdermal estradiol and oral or vaginal natural progesterone: bleeding patterns

Objective To evaluate the effects on bleeding pattern of two different doses of natural progesterone (NP) administered per os or per vagina in association with transdermal estradiol in a continuous, sequential estrogen–progestin therapy.Methods A prospective, randomized trial was conducted on 100 patients randomized into four groups. Each group received transdermal 17β-estradiol treatment at the dose of 50 μg/day. Groups A and B received NP per os at the dose of 100 mg/day and 200 mg/day, respectively. Groups C and D received NP per vagina at the dose of 100 mg/day and 200 mg/day, respectively.Results After 12 cycles of treatment, no significant differences were observed in endometrial thickness between groups, suggesting that all treatments are effective in balancing the effects of estradiol on endometrium. Regarding bleeding control, patients in Groups C and D showed a higher number of episodes of regular bleeding than patients in Groups A and B and fewer episodes of spotting. The better control of bleeding was associated with a higher treatment compliance in patients who received vaginal NP, with a larger percentage of women completing the study.Conclusion Transdermal estrogen replacement therapy combined with 100 mg of micronized NP administered per vagina from the 14th day to the 25th day of each 28-day cycle leads to good cycle control and provides excellent patient satisfaction without serious side-effects. This therapy could be a treatment of first choice in early postmenopausal patients.

Effects of estrogen replacement therapy on estrogen receptor expression and immunoregulatory cytokine secretion in surgically induced menopausal women

To investigate the effect of oral and transdermal estrogen replacement therapy (ERT) on the expression of different estrogen receptor (ER) subtypes and the secretion of immunoregulatory cytokines, we performed a clinical investigation on previously healthy women who had undergone a total hysterectomy and bilateral salpingo-oopherectomy. These women were randomly distributed into two groups: an oral ERT group and transdermal ERT group. Before and after ERT, the serum levels of estradiol (E 2) and follicle stimulating hormone (FSH) were measured, ERα and ERβ expression of peripheral blood T lymphocytes was tested, and secretion of specific immunoregulatory cytokines (IFNγ, IL-2 and IL-4) by T lymphocytes was examined. Our results confirm that for both groups, the serum E 2 level was increased after ERT ( P < 0.01) and the serum FSH level was decreased after ERT ( P < 0.01), with no significant difference in hormone levels between the two groups. ERα expression by T lymphocytes was significantly higher after ERT than before ( P < 0.01) in both groups. Levels of type 1 cytokines (IL-2 and IFNγ), which were secreted by T helper 1 (Th1), after ERT were substantially decreased. The level of type 2 cytokine (IL-4), which were secreted by T helper 2 (Th2), was significantly increased after ERT ( P < 0.01 for the oral group and P < 0.05 for the transdermal group). In summary, both oral and transdermal ERT increased serum E 2 levels, decreased serum FSH levels and relieved the effects of peri-menopausal symptoms. These data suggest that both oral and transdermal ERT act to improve the balance of Th1/Th2 cytokines by the effects of estrogen potentially acting in T lymphocytes mainly through ERα.

Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins

Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins

Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins

Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins

Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins

The role of hormone replacement therapy and estrogen replacement therapy (ERT) in cardiovascular disease prevention has not been unambiguously defined yet. The metabolic effects of estrogens may vary depending upon the route of administration. Therefore, we compared the impact of unopposed oral or transdermal ERT on plasma lipids and lipoproteins in 41 hysterectomized women. This was an open-label, randomized, crossover study (with 2 treatments and 2 periods). The 41 hysterectomized women were randomized to receive oral or transdermal 17 β-estradiol in the first or second of two 12-week study periods. Plasma lipid and lipoprotein levels were assayed before and after each treatment using standard automated methods. Lipid content of lipoprotein subclasses was assessed by sequential ultracentrifugation. The atherogenic index of plasma (AIP) was calculated as log(triglyceride [TG]/high-density lipoprotein [HDL] cholesterol). The difference between the 2 forms of administration was tested using a linear mixed model. The change from baseline for each of the forms was tested using paired t test. Oral ERT resulted in a significant increase in HDL cholesterol and apolipoprotein A-I levels, whereas it significantly decreased total and low-density lipoprotein (LDL) cholesterol and increased TG concentrations. Transdermal ERT had no such effect. Oral ERT led to a significant TG enrichment of HDL (0.19 ± 0.06 vs 0.27 ± 0.07 mmol/L, P < .001) and LDL particles (0.23 ± 0.08 vs 0.26 ± 0.10 mmol/L, P < .001) compared with baseline, whereas transdermal therapy did not have any effect on lipoprotein subclasses composition. The difference between the 2 treatments was statistically significant for HDL-TG and LDL-TG (0.27 ± 0.07 vs 0.19 ± 0.05 mmol/L, P < .001 and 0.26 ± 0.10 vs 0.22 ± 0.07 mmol/L, P< .001, respectively). The transdermal but not oral ERT significantly reduced the AIP compared with baseline (−0.17 ± 0.26 vs −0.23 ± 0.25, P = .023), making the difference between the therapies statistically significant (−0.23 ± 0.25 vs −0.18 ± 0.22, P = .017). Oral administration of ERT resulted in TG enrichment of LDL and HDL particles. Transdermal ERT did not change the composition of the lipoproteins and produced a significant improvement of AIP. Compared with transdermal ERT, orally administered ERT changes negatively the composition of plasma lipoproteins.

Perimenopausal Depression

Perimenopausal Depression

Computer-assisted image analysis of breast fine needle aspiration in a randomized chemoprevention trial of fenretinide vs. placebo in HRT users

Background Digital nuclear morphometric analysis can capture subtle differences along neoplastic progression. Studies showed different profiles from normal to cancer lesions. Our goal is to utilize this method as biomarker in chemoprevention trials. Methods Postmenopausal women were randomized to oral (CEE) or transdermal (E2) estrogen replacement therapy (ERT) in association with fenretinide or placebo. Ultrasound-guided fine needle aspiration (FNA) was performed at baseline and after 12 months in a subset of subjects. Results Ten samples were analyzed by karyometry. E2 compared with CEE increased nuclear area ( p=0.01). A similar pattern was observed for other DNA content and chromatin texture features. Fenretinide vs. placebo, increased nuclear area and shape while decreased slope, peak and entropy. Conclusion Preliminary results indicate that nuclear morphometry is feasible on FNA samples. ERT and fenretinide induced significant karyometric changes. These results support further investigation of this procedure as surrogate biomarker in chemoprevention trial.

Effects of transdermal estrogen therapy on serum paraoxonase activity in hysterectomized postmenopausal women

Effects of transdermal estrogen therapy on serum paraoxonase activity in hysterectomized postmenopausal women

Are Some Types of Hormone Therapy Safer Than Others?

Despite great strides in hormone therapy (HT) research, clinical trial data on the benefit-to-risk profile of different formulations, doses, and routes administration of HT remain lacking. Most of the large-scale clinical trials1–3 have tested oral conjugated equine estrogens with or without medroxyprogesterone acetate, and data on nonoral routes and different types and doses of estrogens and progestogens have been limited. The evidence is mounting that route of delivery and possibly type and dose of HT are important factors, particularly for venous thromboembolism (VTE). Results of clinical trials4,5 and observational studies6 have been concordant in demonstrating an increased risk of VTE with oral exogenous HT. Recent studies suggest that VTE risk may be lower with transdermal than oral estrogen7 and with estrogen alone than with combined therapy.4 However, in the absence of rigorous evidence from large-scale clinical trials on differential effects by hormone formulation or route of delivery, should these findings influence clinical practice? Article p 840 The Estrogen and Thromboembolism Risk (ESTHER) study,7 published in the current issue of Circulation , adds important, relevant data to bolster the case that HT type and route of delivery do indeed make a difference. This well-designed, French, multicenter case-control study of VTE enrolled 271 consecutive cases of VTE in women (age, 45 to 70 years) and matched them to hospital and community controls. Current HT use was present in 46% of the VTE cases compared with 37% of controls. Oral HT users had 4-fold-increased odds of VTE; however, there was no increased risk among transdermal hormone users (odds ratio, 0.9). Previous randomized trials have suggested that the risk of VTE may …

A comparison of raloxifene and calcium plus Vitamin D on vaginal atrophy after discontinuation of long-standing postmenopausal hormone therapy in osteoporotic women: A randomized, masked-evaluator, one-year, prospective study

Objectives: We assessed the effects of the discontinuation of long-standing transdermal estrogen replacement therapy (>4 years) and substitution of this treatment by calcium or raloxifene on the vaginal epithelium and climateric symptoms in a study population of osteoporotic women. Methods: A total of 136 women (mean age 55.5 years) were randomized to calcium (500 mg elemental calcium, 400 IU Vitamin D 3) (n = 40), raloxifene (60 mg/day) (n = 48), or estrogen patches (3.9 mg estradiol) and progesterone (100 mg/day) (n = 48). Treatment was given for 1 year. The vaginal maturation value (VMV), serum estradiol levels, and climateric symptoms using a 12-item modification of the SF-36 quality of life questionnaire were evaluated at baseline and at 6 and 12 months. Results: At 6 months, mean VMV decreased significantly (P < 0.001) in the calcium (−51.8%) and raloxifene (−18.6%) groups compared with baseline and the estrogen/progesterone group. At 12 months, significant decreases of mean VMV in the calcium (−38.7%) and raloxifene groups (−32%) ( P < 0.001) were also observed. Serum estradiol levels and changes of VMV correlated significantly at 6 months ( ρ = 0.361, P < 0.01) and at 12 months ( ρ = 0.269, P < 0.035). A significantly higher number of patients complained of hot flushes and palpitations in the calcium and raloxifene groups than in the estrogen/progesterone group. Raloxifene-treated women reported a significantly higher number of adverse events at 6 months compared to the other treatment groups. Conclusions: Withdrawal and change of long-standing transdermal hormone replacement therapy by treatment with calcium or raloxifene resulted in worsening of vaginal atrophy assessed by the VMV, although it was not clinically perceived by the patients. However, increases in dyspareunia and urinary leaks were reported. Menopausal complaints related to vasomotor symptoms worsened in the calcium- and raloxifene-treated groups and persisted throughout the study period.

Timing of follow-up densitometry in hormone replacement therapy users for optimal osteoporosis prevention

The objectives of the study were (1) to determine the time interval for repeat dual-energy X-ray absorptiometry (DXA) to detect significant bone loss, i.e., greater than the coefficient of variation (CV) of the center (2.8 x CV%) and (2) to assess how long hormone replacement therapy can be maintained to avoid undetected development of low bone mass and to not unduly delay appropriate treatment. A total of 3,826 healthy women, aged 40-65 years, participated in a prospective cohort study, 807 of whom were treated with transdermal estrogen replacement therapy and 626 with transdermal estrogen/progesterone regimens. The untreated group included the remaining 2,393 women. Between 1996 and 2002 they underwent a baseline DXA scan, and DXA scans were then repeated annually. There were no differences among the study groups at entry into the study. Treatment with estrogen was a protective factor for loss of bone mass at the lumbar spine (odds ratio [OR] =0.431, 95% confidence interval [CI] 0.344 to 0.522) and at the femoral neck (OR =0.433, 95% CI 0.352 to 0.521). Treatment with estrogen/progesterone also showed a protective effect against significant changes in follow-up BMD (>2.8 x 1.05% CV of densitometry at L1-L4, >2.8 x 2.3% CV at the femoral neck). In the treated group, significant differences in BMD at the lumbar spine (OR =1.593, 95% CI 1.423 to 2.355) did not appear within the first 3 years, and differences in BMD at the femoral neck (OR =3.555, 95% CI 2.782 to 4.905) did not appear within the first 4 years. It is concluded that in women aged 45-65 years, receiving transdermal hormone replacement therapy without risk factor for loss of bone mass, such as age < 55 years and body mass index <25 kg/m(2), periodical follow-up densitometries would not be necessary, provided that the duration of estrogen or estrogen/progesterone therapy is shorter than 3 years.

Effects of transdermal estrogen replacement therapy on plasma levels of nitric oxide and plasma lipids in postmenopausal women

Objective: Our purpose was to assess the effects of transdermal estrogen replacement therapy (TERT) on plasma levels of nitric oxide (NO) and plasma lipids in postmenopausal women. Materials and methods: The study designed as a randomized, double-blind, placebo-controlled trial, involved 43 postmenopausal healthy women who had previously undergone hysterectomy. Women received either transdermal 100 μg 17β-estradiol (Climara forte TTS ®) or placebo once a week for 3 months. Plasma levels of NO metabolites, estradiol (E 2), total cholesterol (TC), triglicerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), HDL 2 and HDL 3 were measured in blood samples of all women which were collected before, after 24 h and after 3 months of therapy. Results: We found significantly increased NO levels 24 h after therapy in TERT group. Moreover significantly higher NO levels were determined at 3rd month of therapy. Serum HDL and HDL 2 levels of ERT group were significantly increased at 3rd month of therapy. Alteration of serum levels of HDL 3, LDL and TC were not significantly different in groups. TG levels were significantly decreased in TERT group. Discussion: NO-related mechanism may help to explain the cardio-protective effect of TERT in the postmenopausal period. TERT seems to have favorable effects on plasma lipids in surgical menopausal women.

Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women

The complex relationship between sex hormones and immune function suggests that sex hormone deficiency and estrogen replacement therapy (ERT) in post-menopausal women may have pleiotropic effects on immune function. For this reason, we aimed to investigate short-term effects of surgical menopause and ERT on immunity profile in peri-menopausal women. Seventeen healthy peri-menopausal women who were to undergo total abdominal hysterectomy and bilateral salpingo-oopherectomy (TAH + BSO) for uterine myoma were enrolled into this study. Three blood samples were collected from each patient: 1-day prior to surgery, 30 days after the operation (before ERT) and 30 days after transdermal ERT. The percentages of peripheral blood lymphocyte subpopulations, serum interleukin-4 (IL-4) and interferon-gamma (IFN-γ) concentrations were determined by flow-cytometry and ELISA, respectively. Following TAH + BSO, the percentage of CD8 + cells was increased ( P<0.001) while the percentage of CD19 + cells, serum IL-4, and IFN-γ concentration and the ratio of CD4 + to CD8 + cells were decreased ( P<0.001, P<0.001, P<0.002, and P<0.05, respectively ). After ERT, this trend reversed and a decrease in the CD8 + cells ( P<0.001), increase in the CD19 + cells percentages ( P<0.02) and increase in serum IFN-γ concentration ( P<0.002) were observed. Although an increasing trend in the CD4 + to CD8 + ratio occurred by ERT, this was not significant. However, the decrease in the serum IL-4 concentration after TAH + BSO was not reversed by ERT. Hormone deficiency in post-menopausal women may cause an impaired immune response, and ERT can restore this phenomenon. Estrogen seems to have an important role in the regulation of immune function.

Differential effects of oral vs. transdermal estrogen replacement therapy on serum amyloid a in postmenopausal women

P-583 Key Words: Estrogen, Inflammation, HDL

Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women

The complex relationship between sex hormones and immune function suggests that sex hormone deficiency and estrogen replacement therapy (ERT) in post-menopausal women may have pleiotropic effects on immune function. For this reason, we aimed to investigate short-term effects of surgical menopause and ERT on immunity profile in peri-menopausal women. Seventeen healthy peri-menopausal women who were to undergo total abdominal hysterectomy and bilateral salpingo-oopherectomy (TAH + BSO) for uterine myoma were enrolled into this study. Three blood samples were collected from each patient: 1-day prior to surgery, 30 days after the operation (before ERT) and 30 days after transdermal ERT. The percentages of peripheral blood lymphocyte subpopulations, serum interleukin-4 (IL-4) and interferon-gamma (IFN-γ) concentrations were determined by flow-cytometry and ELISA, respectively. Following TAH + BSO, the percentage of CD8 + cells was increased ( P <0.001) while the percentage of CD19 + cells, serum IL-4, and IFN-γ concentration and the ratio of CD4 + to CD8 + cells were decreased ( P <0.001, P <0.001, P <0.002, and P <0.05, respectively ) . After ERT, this trend reversed and a decrease in the CD8 + cells ( P <0.001), increase in the CD19 + cells percentages ( P <0.02) and increase in serum IFN-γ concentration ( P <0.002) were observed. Although an increasing trend in the CD4 + to CD8 + ratio occurred by ERT, this was not significant. However, the decrease in the serum IL-4 concentration after TAH + BSO was not reversed by ERT. Hormone deficiency in post-menopausal women may cause an impaired immune response, and ERT can restore this phenomenon. Estrogen seems to have an important role in the regulation of immune function.