Transdermal Estradiol Treatment Research Articles

Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women – A randomized clinical trial

BackgroundThe menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown. This study aimed at determining relationships between E2 fluctuations, mood symptoms, and physiologic stress-reactivity (cortisol and interleukin-6) and whether differences in mood-sensitivity to E2 fluctuations predict mood responses to TE2 treatment. MethodsThis randomized, double-blind, placebo-controlled trial investigated medically healthy women (46–60 years) in the early or late menopause transition. Baseline E2-sensitivity strength was calculated from eight weekly individual correlations between week-to-week E2 change and index week anxiety (State-Trait Anxiety Inventory) and anhedonia (Snaith-Hamilton Pleasure Scale). Women then received eight weeks of TE2 or transdermal placebo. ResultsAnalyses included 73 women (active TE2 n = 35). Greater baseline E2 fluctuations predicted greater anhedonia (p = .002), particularly in women with more SLEs. Greater E2 fluctuations also predicted higher cortisol (p = .012) and blunted interleukin-6 (p = .02) stress-responses. Controlling for baseline symptoms, TE2 was associated with lower post-treatment anxiety (p < .001) and anhedonia (p < .001) versus placebo. However, the efficacy of TE2 for anxiety (p = .007) and also for somatic complaints (p = .05) was strongest in women with greater baseline E2 sensitivity strength. ConclusionsTE2 treatment reduced perimenopausal anxiety and anhedonia. The ability of baseline mood-sensitivity to E2 fluctuations to predict greater TE2 efficacy has implications for individualized treatment of perimenopausal anxiety disorders.

368. Maternal mental health (mama) trial evaluating short-term estrogen as a strategy to prevent postpartum depression in high-risk women: Protocol for a double-blind, randomized, placebo-controlled trial

Introduction and aims of the study:Perinatal depression affects 10–15% of women postpartum and has a recurrence rate of 40% in subsequent pregnancies. Women who develop perinatal depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of three weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression.

Short-term oestrogen as a strategy to prevent postpartum depression in high-risk women: protocol for the double-blind, randomised, placebo-controlled MAMA clinical trial

IntroductionPostpartum depression affects 10%–15% of women and has a recurrence rate of 40% in subsequent pregnancies. Women who develop postpartum depression are suspected to be more sensitive to the rapid...

Transdermal estradiol as a novel treatment for Peyronie's disease: A case report

Introduction: This is a single‐patient case report of a (now) 75-year old married male with long-standing Peyronie’s disease (PD). The patient’s main symptoms were painful erections as well as secondary anxiety and depression. Resolution of these symptoms was achieved with transdermal estradiol treatment.&#x0D; Objectives: To describe a patient with PD, whose persistently painful erections and psychologic distress were eliminated by a novel treatment involving transdermal estradiol. This report also aims to present a novel treatment for patients with paraphilias.&#x0D; Methods: An interview with the patient, chart review, and a literature search were conducted. Informed consent was obtained from the patient and this report was approved by the Research Ethics Committee at the Royal Hospital in Ottawa.&#x0D; Results: Treatment with transdermal estradiol decreased the patient’s sex drive and virtually eliminated his erections with no undesirable side effects. The patient and his wife still enjoy sexual relations without the need for penile erection.&#x0D; Conclusions: This case report presents a novel treatment for PD. It also introduces a novel method to treat men who wish to decrease their sex drive (e.g. men with paraphilic disorders). Replication of this treatment intervention in men with PD and new studies of its use in men with paraphilic disorders are warranted.

Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress.

Endothelial function declines progressively across stages of the menopause transition; however, the mechanisms contributing to this decline are unknown. We hypothesized that differences in endothelial function among pre-, peri, and postmenopausal women are related to differences in estradiol and oxidative stress. Brachial artery flow-mediated dilation (FMD) was measured in 87 healthy women categorized by menopause stage (24 premenopausal, 17 early and 21 late perimenopausal, and 25 postmenopausal) before and after 3 days of ovarian hormone suppression (gonadotropin releasing hormone antagonist [GnRHant]) alone, and an additional 3 days of GnRHant with concurrent transdermal estradiol or placebo add-back treatment. In 82 women, FMD during acute vitamin C (antioxidant) infusion was measured before and after GnRHant + add-back. Before GnRHant, FMD was different among groups (p < 0.005; reduced across stages of menopause). Vitamin C increased FMD in late peri- and post- (p < 0.005) but not pre- or early perimenopausal women (p > 0.54). After GnRHant alone, FMD decreased in pre- and peri- (p < 0.01), but not postmenopausal women, and was restored to premenopausal levels by estradiol add-back in the pre- and perimenopausal groups. Vitamin C improved FMD in pre-, peri-, and postmenopausal women on GnRHant + placebo. There was no effect of vitamin C on FMD in women on GnRHant + estradiol. These observations support the concept that the decline in endothelial function across the menopause transition is related to the loss of ovarian estradiol. The decline in estradiol may alter redox balance, thereby increasing oxidative stress and impairing endothelial function.

Effect of transdermal estradiol therapy on bone mineral density of amenorrheic female athletes.

The effects of transdermal estradiol treatment (HT) in amenorrheic athletes (AA) with low body weight (BW) and low bone mineral density (BMD) are unknown. To investigate whether HT increases BMD in AA with low BW and to compare the results with levels in AA who have recovered spontaneous menstruation (SM). Female athletes (n=151) were recruited at the Japan Institute of Sports Sciences and the University of Tokyo. All participants were divided into four groups: an AA group (untreated group) (n=36), a HT group (n=55), a SM group (n=21), and an eumenorrheic athletes (EA) group (n=39). Height, body weight, blood tests, and dual-energy X-ray absorptiometry were measured at baseline and after 12months. The HT group was treated daily for 12months with transdermal estrogen therapy. In addition, participants received oral progestin for 7days once every 3months. After 12months, BMD in the AA group was significantly lower than at baseline; however, BMD in the other three groups was significantly higher than at baseline. The ratio of the change in BMD values before and after 12months was -1.6±3.2% for the AA group, 5.3±8.7% for the HT group, 11.1±8.9% for the SM group, and 2.3±5.7% for the EA group. The rate of change in BMD values in the SM group was greater than that in the HT group. HT increased BMD in AAwith low BW, and the increase in those with SM was greater than that in those treated with HT.

P155 Transdermal oestrogen prevents cyclically-recurrent genital herpes: Abstract P155 Table 1

<h3>Background</h3> Some women suffer cyclical recurrences of genital herpes (c-RGH) immediately prior to menstruation, which are effectively prevented using aciclovir in the luteal phase only. This is more likely to occur in perimenopausal women whose immunity is diminished by premenstrual dysphoric disorder (PMDD), which is treatable with transdermal estradiol. <h3>Aim</h3> To observe the frequency of herpes recurrences in women commencing estradiol treatment for perimenopausal PMDD. <h3>Methods</h3> 12 perimenopausal women median age 41 years (range 36–45) presented between 2006–15, each meeting the criteria for PMDD subsequently defined in DSM-5. Each had at least 4 consecutive monthly episodes of c-RGH (culture-proven HSV2) before some took luteal-phase aciclovir, then all switched to transdermal 17-beta estradiol gel 0.5mg daily for 14 days in the luteal phase or continuously for those using Mirena. Subjects self-reported mood with a modified daily symptom chart and herpetic symptoms over 9 months follow-up during which no aciclovir was taken pre-emptively. Intention-to-treat analysis included 10 cycles where treatment was omitted in error and both conditions recurred. <h3>Results</h3> All women experienced substantial or complete relief of PMDD in all but three treated cycles. Only 13 symptomatic c-RGH episodes occurred on treatment in 108 woman-months’ observation. <h3>Conclusion</h3> Transdermal estradiol treatment is a novel and biologically plausible method of preventing cyclically-recurrent genital herpes as it stabilises the hormonal milieu and diminishes immune suppression caused by PMDD.

Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations

We examined estradiol (E2) and estrone (E1) concentrations in breastfeeding mother-infant dyads. The mothers had postpartum depression and were participants in a randomized clinical trial with three treatments (transdermal E2, sertraline, and placebo). Neither infant E1 and E2 concentrations nor infant growth differed across the treatments. Transdermal E2 administration of 50 to 200 mcg/day for breastfeeding women did not affect infant E1 or E2 concentrations or infant growth.

Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women

Decreases in estrogen levels contribute not only to early postmenopausal bone loss but also to bone loss with aging. While estrogen is critical for the maintenance of bone formation, the mechanism(s) of this effect remain unclear. Thus, we assessed the effects of 4months of transdermal estradiol treatment (0.05mg/day) of postmenopausal women as compared to no treatment (n=16 per group) on the expression of genes in pre-specified pathways in freshly isolated bone marrow osteoprogenitor cells (hematopoietic lineage [lin]-/Stro1+). We also evaluated whether estrogen treatment modulated peripheral blood or bone marrow plasma levels of the Wnt antagonists, sclerostin and DKK1, as well as serotonin, OPG, RANKL, adiponectin, oxytocin, and inflammatory cytokines (TNFα, IL-1β, and IL-6), as each of these molecules have recently been shown to play an important role in regulating osteoblast function and/or being responsive to estrogen. We observed a significant decrease in the expression of several proliferation markers (cyclin B1, cyclin E1, E2F1) and increase in adhesion molecules (N-cadherin) in bone marrow lin-/Stro1+ cells from estrogen-treated compared to control women. None of the peripheral blood or bone marrow plasma marker levels differed between the two groups, with the exception of sclerostin levels, which were significantly lower in the estrogen-treated as compared to the control women in peripheral serum (by 32%, P=0.009) and in bone marrow plasma (by 34%, P=0.017). There were significant differences in bone marrow versus peripheral plasma levels of several factors: sclerostin and OPG levels were higher in bone marrow as compared to peripheral plasma, whereas serotonin and adiponectin levels were higher in peripheral as compared to bone marrow plasma. In summary, our data directly assessing possible regulation by estrogen of osteoprogenitor cells in humans indicate that, consistent with previous studies in mice, estrogen suppresses the proliferation of human bone marrow lin-/Stro1+ cells, which likely represent early osteoprogenitor cells. Further animal and human studies are needed to define the role of the changes we observed in mRNAs for adhesion molecules in these cells and in local sclerostin production in bone in mediating the effects of estrogen on bone metabolism in humans.

Depot-Medroxyprogesterone Acetate and Endothelial Function Before and After Acute Oral, Vaginal, and Transdermal Estradiol Treatment

Young women using depot-medroxyprogesterone acetate (DMPA) contraception have low circulating estrogen and elevated synthetic progestin. Low estrogen and certain progestins have been shown to impact endothelial function even in young healthy women. The purpose of this study was to investigate how DMPA affects endothelial function and serum biomarkers of cardiovascular risk before and after acute oral, vaginal, and transdermal estradiol treatments. Seven young women participated on 3 study days during a normal 12-week DMPA cycle, during weeks 3, 6, and 9. An additional 8 young women participated on 6 separate days during a 12-week DMPA cycle, 3 times on DMPA only and 3 times when using DMPA plus acute estradiol treatments. Wall tracking of high-resolution ultrasound images of the brachial artery were used during endothelium-dependent flow-mediated dilation and nitroglycerin administration to test endothelial function. Serum samples were analyzed for cardiovascular indexes at each study visit. All of the estradiol treatments increased endothelium-dependent flow-mediated dilation compared with DMPA only (P<0.001). Endothelium-dependent flow-mediated dilation was not different among DMPA-only treatment days. Endothelium-independent vasodilation and cholesterol levels were unchanged across DMPA-only and DMPA plus estradiol cycles. These data suggest that acute estradiol treatments improve endothelium-dependent flow-mediated dilation in young hypoestrogenic women using DMPA.

A Prospective Study of Hormone Therapy and Depression in Community-Dwelling Elderly Women

The potential benefits of hormone therapy (HT) in treating depressed postmenopausal women are controversial, and data on depression (re)emergence in the context of HT discontinuation are lacking. To determine whether HT is associated with a modified risk of new-onset depressive symptoms in elderly women. Current depressive symptomatology was evaluated in 4,069 community-dwelling postmenopausal women aged 65 years and over who were randomly recruited from 3 French cities between 1999 and 2001. Depressive symptomatology was assessed using the Center for Epidemiologic Studies-Depression Scale at baseline and as part of the 2- and 4-year follow-up. Over the follow-up period, multivariate logistic regression analyses adjusted for sociodemographic variables, measures of physical health, and cognitive impairment failed to find a significant association between HT at baseline and the incidence of depressive symptoms. However further analysis indicated an increased risk of incident depressive symptoms for women using transdermal estradiol treatment combined with synthetic progestin specifically (odds ratio [OR] = 1.59; 95% CI, 1.01-2.50; P = .046). In addition, while women taking HT continuously over the 4-year follow-up did not show an increased risk of depressive symptoms, women who stopped their treatment early after study inclusion, had a significantly higher risk (OR = 2.63; 95% CI, 1.52-4.55; P = .0005). Hormone therapy was not associated with a protective effect against the emergence of depressive symptoms in elderly postmenopausal women. However, discontinuing treatment could increase the risk of depressive symptoms. Data on the appropriate management of depression in the context of HT discontinuation among postmenopausal women require further investigation.

Aromatase deficiency in men: a clinical perspective

Human aromatase deficiency is a very rare syndrome characterized by congenital estrogen deprivation that is caused by loss-of-function mutations in CYP19A1, which encodes aromatase. Here, we review the presentation, diagnosis and treatment of aromatase deficiency in men to provide useful advice for clinical management of the condition. At presentation, all men with aromatase deficiency have tall stature, delayed bone maturation, osteopenia or osteoporosis and eunuchoid skeletal proportions. Diagnosis of the condition is supported by the presence of unfused epiphyses and undetectable serum estradiol levels; the condition can be further substantiated by genetic sequencing of CYP19A1. Transdermal estradiol treatment at a daily dose of about 25 microg might be adequate for lifelong replacement therapy. BMD and levels of serum estradiol, luteinizing hormone and testosterone should be monitored carefully and considered powerful biochemical markers of adequate estrogen substitution in clinical practice. Early diagnosis is important to initiate estrogen therapy as soon after puberty as possible to avoid the skeletal complications that are associated with this condition.

Low-dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

The aim of this study was to investigate whether transdermal low-dose estradiol treatment induces changes in mammographic density or heterogeneity compared with raloxifene, whether if these changes relate to changes in bone formation/resorption markers, and whether these findings indicate elevation of breast cancer risk by treatment. Digitized mammograms of 2 x 135 completers of a 2-year, randomized trial formed the base of the present analysis. Active treatments were transdermal estradiol releasing 0.014 mg estradiol (E2)/week and orally administered raloxifene hydrochloride 60 mg/day, respectively. Influence of the therapies on breast density was assessed with categorical scores Breast Imaging Reporting and Data System, area percentage density, and computer-based (E2-specific) heterogeneity examination of radiographs. These where related to physical and systemic markers. At baseline, no mammography scoring methodology or other marker could separate the two treatment groups of transdermal estradiol and raloxifene. No treatment induced significant density changes measured by Breast Imaging Reporting and Data System. Both treatments made the area percentage density increase and the estradiol significantly. Both treatments induced significant changes in E2-specific heterogeneity scoring (E2-specific heterogeneity examination of radiograph), and the raloxifene treatment induced a significantly higher change. At baseline, the mammographic markers showed negative correlation with body mass index and positive correlation with serum type I collagen crosslinks C-telopeptide. The changes in mammographic markers did not essentially exhibit correlations to changes in bone markers in either treatment group. Low-dose transdermal estradiol and raloxifene induced comparable changes in breast density and heterogeneity. Baseline correlations may be explained through relations to obesity. The current study does not yield evidence against the hypothesis that "neither raloxifene nor low dose transdermal estradiol treatment increases the breast cancer risk."

The effects of long-term raloxifene and estradiol treatments on bone in a patient with congenital aromatase deficiency

Introduction In adult aromatase-deficient men, estrogen treatment has always resulted in a rapid skeletal maturation with epiphyseal closure and improved BMD. Raloxifene is a SERM with proven estrogen agonist action on bone that leads to an improvement in BMD and a reduction in bone turnover. The present study reports the effects of raloxifene and transdermal estradiol treatment, respectively, on epiphyseal closure and BMD in an aromatase-deficient man, over a 24-month follow-up, with the aim of obtaining further insight into the role of estrogens in the male skeletal homeostasis. Materials and methods A 25-year-old Caucasian man with aromatase deficiency, a bone age of 15.3 years, unfused epiphyses and an impaired BMD was initially administered raloxifene (60 mg/day per os) for 12 months, while transdermal estradiol (25 μg twice weekly) was administered for the subsequent 12 months. During the follow-up, the effects of the two treatments on epiphyseal closure, BMD and bone turnover markers were investigated. An iliac crest bone biopsy was performed only before and after the raloxifene treatment, but it was not repeated after transdermal estradiol treatment. Results No changes in bone age were observed after raloxifene therapy, whereas a complete epiphyseal closure was achieved with transdermal estradiol treatment. Compared with baseline values, raloxifene treatment led to improved BMD both at the ultradistal forearm and 33% radius; the transdermal estradiol treatment resulted in a further slight increase in BMD at the 33% radius, but not at the ultradistal forearm. The baseline bone biopsy showed elevated bone remodelling in trabecular bone, while the second biopsy following raloxifene treatment revealed a decrease in remodelling. Discussion This study shows that the management of aromatase deficiency in the male cannot consider raloxifene as a first choice treatment, but should be still based on estrogen replacement treatment since in this patient the completion of bone maturation has only been obtained once estradiol substitution was performed. The present case also demonstrates that raloxifene is able to improve BMD in aromatase-deficient men.

Hypothalamic–pituitary–gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback

In men, the feedback of gonadotropins is regulated by estrogens that come from the aromatization of testosterone, but the relative contribution to the inhibition of LH and FSH secretion by the amount of locally produced estrogens within the hypothalamus and/or the pituitary, and the amount of circulating estrogens still remains unknown. In order to evaluate the effect of regulation induced by estradiol on the hypothalamic-pituitary-gonadal (HPG) axis, we studied the pulsatility of LH and FSH in two aromatase-deficient men (called subject 1 and subject 2), in which the production rate of estrogen (both local and circulating) is completely, or at least severely, impaired. FSH and LH were evaluated in terms of their pulsated secretion and as GnRH-stimulated secretion in two phases: phase 1, before estrogen treatment; and phase 2, during estrogen treatment with 25 microg transdermal estradiol twice weekly. Blood samples were taken during phase 1 and phase 2 at 0800 h for basal measurements of LH, FSH, inhibin B, testosterone, and estradiol. The analysis of the pulsatility of LH and FSH was performed by sampling every 10 min for 8 h in the two phases. Gonadotropin response to GnRH-stimulation test was studied by serial standard sampling after 100 microg GnRH i.v. bolus in phases 1 and 2. Estrogen treatment led to a significant reduction in both LH-pulsated frequency (7.5 +/- 0.7 in phase 1, 4.5 +/- 0.7 in phase 2) and amplitudes (3.5 +/- 0.006 in phase 1, 1.9 +/- 0.4 in phase 2) of peaks, whereas FSH showed only a conspicuous reduction in serum levels and a trend towards the reduction of the amplitudes of its peaks without modification of the frequency of the pulses. Both testosterone and gonadotropins decreased during phase 2, whereas estradiol reached the normal range in both subjects. Transdermal estradiol treatment significantly lowered the peaks of both serum LH and FSH after GnRH as well as the incremental area under the curve after GnRH administration in both subjects. Basal serum inhibin B levels were slightly higher before transdermal estradiol treatment (phase 1) than during estrogen treatment (phase 2) in both subjects. The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of the frequency of LH pulses. The present study, coupling the outcomes of basal, GnRH-stimulated and the pulsatile evaluation of LH and FSH secretion in two aromatase-deficient men, demonstrates that circulating estrogens play an inhibitory role in LH secretion by acting on the hypothalamus and the pituitary gland of men. The discrepancy among testosterone levels, the arrest of spermatogenesis and a slightly inappropriate respective increase of serum FSH (lower than expected) suggests a possible role of estrogens in the priming and the maturation of HPG axis in men, an event that has never occurred in these two subjects as a consequence of chronic estrogen deprivation.

Sex steroids and sexual desire in a man with a novel mutation of aromatase gene and hypogonadism

Sexual behavior was investigated by a sexological interview in a man with aromatase deficiency and hypogonadism. The study was performed at the end of a long testosterone treatment, during transdermal estradiol treatment and during estradiol and testosterone associated treatment. Sexual behavior did not show abnormalities. As assessed by a sexological interview and by a sexological questionnaire gender-identity was male, sexual orientation was heterosexual and libido was normal. Sexual function was limited to masturbation and was seemingly unaffected by testosterone or estradiol alone; only the associated treatment induced a great increase in libido and in frequency of masturbation and sexual fantasies when both testosterone and estradiol reached the range of normality. Sexual behavior is mainly under the control of cognitive functions in men, but sex steroids may modulate some aspects of male sexuality. Our findings suggest that in men estrogens could play a role in sexual activity.

Transdermal estradiol treatment suppresses serum gonadotropins during lactation without transfer into breast milk

To determine which dose of transdermal E(2) could be administered to breastfeeding women without significant transfer into breast milk. Single center, prospective study. University hospital research unit. Twenty-one healthy breastfeeding women (aged 20-38 years) who had delivered 20 weeks earlier. Treatment with either 50, 75, or 100 microg/24 hours of transdermal E(2) or placebo for 2 weeks beginning at 20 weeks postpartum. Breast milk and blood samples were collected before the treatment and 2 weeks into the treatment. Serum and milk E(2) were measured by RIA after diethyl ether-ethyl acetate extraction. Serum inhibin B concentrations were measured by ELISA and serum FSH and LH concentrations were measured by fluoroimmunoassay. None of the breast milk samples contained any measurable concentrations of E(2) after E(2) treatment. Serum E(2) concentrations were elevated in a dose-dependent manner. Both serum FSH and LH concentrations were decreased in all treatment groups with a more pronounced suppression in the 75 and 100 microg/24-hour groups. Serum inhibin B concentrations were not significantly suppressed during the study. Three of six women using the 100 microg/24-hour E(2) dose discontinued the study due to side effects. A dose as high as 100 microg/24 hours of E(2) can be administered transdermally without traces appearing in the breast milk. Whether the symptoms associated with the hypoestrogenic state of lactation can be alleviated by transdermal E(2) treatment (50 or 75 microg/24 hours) can now be studied in the early postpartum phase (6 weeks onward).

The effect on cartilage of different forms of application of postmenopausal estrogen therapy: comparison of oral and transdermal therapy

The effect on urine C-telopeptides of type II collagen (uCTX-II) of oral and transdermal estradiol treatment was compared using samples from two randomized, double-blind, placebo-controlled trials. A total of 171 healthy, Danish postmenopausal women, 45–65 years of age completed the 2-year study periods. The uCTX-II marker assessed cartilage degradation, and this response was compared with the effect on urine C-telopeptides of type I collagen (uCTX-I), considered a specific marker of bone resorption. Doses in the oral estradiol treatment groups (continuous combined therapy) were 1 mg 17-β-estradiol + 1 mg drosperinone or 1 mg 17-β-estradiol + 2 mg drosperinone or 1 mg 17-β-estradiol + 3 mg drosperinone or placebo. Doses in the transdermal estradiol treatment groups (continuous combined therapy) were 45 μg 17-β-estradiol + 30 levonorgestrel or 45 μg 17-β-estradiol + 40 μg levonorgestrel or placebo. The effect of oral and transdermal estradiol therapy on cartilage degradation was reflected as a decrease of 19–30% in uCTX-II ( P = 0.02 and P = 0.003 vs. placebo) after 1 year of treatment. uCTX-I decreased 70% ( P < 0.0001 vs. placebo) reflecting a pronounced effect on bone resorption that was consistent with a 2-year increase in spine and hip BMD of 7–8% and 4–6%, respectively. The results indicate that different regimens of postmenopausal HRT both have an effect on cartilage and bone thus protecting against osteoporosis and osteoarthritis (OA). However, long-term clinical trials are needed to further investigate this issue.

Effects in post-menopausal women of transdermal estrogen associated with progestin upon the removal from the plasma of a microemulsion that resembles low-density lipoprotein (LDL)

Objective: To evaluate the effects of transdermal estradiol and medroxyprogesterone acetate (MPA) treatment on the removal from the plasma of a cholesterol-rich microemulsion (LDE) that roughly resembles low-density lipoprotein (LDL) structure and that binds to LDL receptors. Methods: Ten healthy post-menopausal women were studied before and after 3-month treatment with transdermal estradiol in the following dosages administered every 3.5 days: 25, 50, 50, 100, 100, 50, 50 and 25 μg. From the 15th to the 21st day and from the 22nd to the 28th day of estrogen treatment, respectively, 10 and 5 mg q.d. MPA per oral were associated to the transdermal estrogen. The emulsion labeled with 14 C -cholesteryl oleate was injected after 12 h fasting and its fractional catabolic rate (FCR) was calculated from the plasma decaying curves of the isotope. Results: Treatment reduced LDL-cholesterol levels by 8% only (149.0 ± 36.0 mg/dl, 138.0 ± 27.0 mg/dl; P = 0.046), but the FCR of LDE expressed in medians (25%; 75%) increased from 0.0054 (0.003; 0.052) h −1 to 0.021 (0.009; 0.10) h −1, P = 0.002. Conclusion: The association used in this study so as to mimic the increasing–decreasing pattern of the hormonal ovarian production reduced modestly LDL-cholesterol levels but pronouncedly increased the lipoprotein removal as tested by LDE FCR.

Effect of different hormone replacement therapy regimens on circadian blood pressure profile and active renin in postmenopausal women

Hormone replacement therapy (HRT) was considered as main prevention of cardiovascular disease (CVD) in postmenopausal women. Mechanisms of vasoprotective effect of this treatment are complex. However, recent data give rise to some uncertainties about HRT benefits and risks. Little is known about the effects of oral and transdermal HRT regimens on the renin-angiotensin-aldosterone system (RAS) and blood pressure (BP). This 3-month study comprised 28 menopausal women (age range 45-55 years) divided into two groups: Group 1: 12 normotensive women with natural occurrence of menopause receiving oral treatment with Climen® (Schering) containing estradiol valerate and cyproterone acetate; Group 2: 16 normotensive women with surgically induced menopause receiving transdermal application of Climara® (Schering) containing 17β-estradiol. There were no significant differences in office BP before and after treatment with Climara or Climen. However, ambulatory monitoring showed a significant fall in systolic BP (day-time, night-time and total 24-h) when estradiol alone was used. A similar trend towards lower values of systolic BP that was significant only for the night-time BP was observed after treatment with Climen. There were no significant changes in diastolic BP after both treatment regimens. Heart rate (day-time and 24-h) was significantly lower after transdermal estradiol treatment. There was no significant change in active renin after both treatment regimens. The present study showed that both treatment regimens resulted in lower ambulatory BP in normotensive postmenopausal women with more notable reduction in night-time BP. Increase in nocturnal dipping may account in part for the beneficial cardiovascular effects of HRT including decreased end-organ damage.