Vaginal Estradiol Research Articles

Artificial versus stimulated cycles for endometrial preparation prior to frozen–thawed embryo transfer

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen–thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9–10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 ± 1.1 mm versus 8.7 ± 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) ( P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.

Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine insemination

This pilot study was conducted to compare the results of intrauterine insemination (IUI) under ovarian stimulation with either letrozole (Femara) or human menopausal gonadotrophin (HMG). A randomized controlled trial was conducted. Eighty women aged 20–35 years with unexplained infertility of at least 2 years' duration were randomized according to a computer-generated randomization list into the letrozole group and the HMG group. Letrozole was administered at 5 mg/day from day 3 to day 7 of the IUI cycle. HMG injections were started on day 3 at a dose of 75 IU for women under 30 years old and 150 IU for women over 30 years old and monitored periodically by vaginal ultrasound and oestradiol concentrations. The variables selected for analysis were clinical pregnancy rate, endometrial thickness, length of follicular phase and number of preovulatory follicles. No statistically significant difference in clinical pregnancy rates per cycle was found for patients in the letrozole or HMG group (18.4 versus 15.7%). Cost was significantly higher in the HMG stimulation cases ( P < 0.001) and no injections were required in the letrozole group. In conclusion, letrozole offers a new treatment regimen in ovarian stimulation regimens for IUI that is cost effective, simple and convenient for the patients.

Alteração do epitélio vaginal em fêmeas crioulas com ovulação durante a lactação

O objetivo deste estudo foi identificar mudanças do epitélio vaginal em fêmeas de "Cerdo Pelón Mexicano", que ovularam durante o lactação, estágio causado pelo efeito da presença de macho e retirada da leitegada. A avaliação do estro foi feita através de citologia de raspado vaginal, observação do comportamento das fêmeas e por determinação de 17 ß estradiol e de progesterona no 8º dia após o início de lactação. Foram formados quatro grupos de fêmeas: Grupo 1 não sofreu estímulo; Grupo 2 permaneceu com o macho; Grupo 3 foi separado sua leitegada por 4 h e grupo 4 recebeu ambos estímulos. Amostras de raspado vaginal foram coletadas a cada 24 horas durante 5 dias após o estímulo. ANOVA para amostras repetidas foi realizada durante os 5 dias do teste. O estímulo utilizado no Grupo 4 causou modificações significativas (P &lt; 0·001) quando comparado aos Grupos 1, 2 e 3. Os níveis de estradiol foram mais altos que 30 pg/ml no Grupo 4 no 10º dia pós parto e 4.5 ng/ml de progesterona nos 11º e 12º dias pós parto. Ficou evidente que 100% das fêmeas nos Grupos 1, 2 e 3 não mostraram atividade de estro quando foi relacionado citologia vaginal com o comportamento estral e determinação hormonal da fase de lactação das fêmeas, ao passo que 100% das fêmeas no Grupo 4 apresentaram estro 72 horas após os estímulos e ovularam 24 a 36 horas do início do cio, o que foi comprovado pela determinações de estradiol e progesterona, respectivamente.

Fraktionierte Anwendung einer 17β Estradiolcreme zur Behandlung der atrophischen Kolpitis postmenopausaler Frauen

Purpose: The study was performed to evaluate the efficacy and safety of locally applied estradiol cream (Linoladiol® N) on vaginal atrophy in postmenopausal women in fractionated use. Material and Methods: In a randomized, double-blind, placebo-controlled parallel group study, 48 postmenopausal women self-administered 2 g of the test preparation (= 200 μg estradiol) for 4 weeks and placebo cream as well. In the first week, the creams were used thrice in 48-hour intervals. In the weeks 2 - 4, the application intervals were 3 and 4 days, respectively (twice weekly). The primary endpoint was the change in the vaginal maturation index (VMI). Secondary endpoints were clinical improvement of atrophy, vaginal pH, and number of lactobacilli. For safety assessment the serum levels of E2, FSH, LH, and SHBG were determined. The thickness of the endometrium was controlled sonographically and unexpected events were monitored systematically. Results: The estradiol treatment resulted in an increase in the VMI from 24.47% on day 1 to 64.23% on day 31. This is an enhancement of 39.56%. Under placebo, the change in VMI amounted only 5.16%. The difference between active treatment and placebo is highly significant (p < 0.0001). The improvement of vaginal cytology was mostly due to an increase in the superficial cells and a concomitant decrease in the basal and parabasal cells. In parallel, the use of estradiol improved the clinical symptoms of atrophy markedly. The mean pH value diminished in the treatment group from pH 6.0 to pH 4.2, correlated with a high proliferation of lactobacilli. During local treatment, the mean E2 plasma level increased slightly from 6.4 pg/ml to 15.1 pg/ml on day 31. The levels of FSH, LH, and SHBG were not significantly changed. There was no relevant change in mean endometrium thickness. The tolerability of the creams was good; there were no severe unexpected events. Conclusion: The results indicate that the fractionated use of vaginal estradiol cream (Li-noladiol® N) causes rapid and extensive improvement of vaginal atrophy. This method of treatment can be considered safe.

Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet

Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring (ESTring) to that of a vaginal estradiol tablet (Vagifem®) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency. Quality of life and acceptability of treatment delivery were also assessed.Study design A prospective, randomized study in which women were assigned in a 2 : 1 ratio to ESTring and Vagifem and followed for 12 months. The primary endpoint was endometrial safety, based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48. Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3, 12, 24, 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline, 12 and 48 weeks. In addition, pelvic floor strength, vaginal cytological evaluation and pH, bacteruria and patient acceptability were assessed. Quality of life was assessed using a menopause-specific quality-of-life questionnaire and a 2-day bladder diary at baseline and 12 and 48 weeks. The comparability of the two groups was assessed using ANOVA, χ2 or Fisher's exact tests.Results A total of 126 women were randomized to ESTring and 59 to Vagifem. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency. Maturation indices increased in both groups, from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks. After 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. A statistically smaller proportion of bleeding/spotting occurred in the ESTring group (n = 0) compared to the Vagifem users (n = 4). Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range. General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups. Bladder diary variables showed no differences between treatment groups.Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.

Recombinant gonadotrophin-based, ovarian hyperstimulation syndrome-free stimulation of the high responder: suggested protocol for further research

Ovarian stimulation of the high responder remains controversial. The narrow margin between a too low gonadotrophin dose (and abnormal oestradiol rise) and excessive stimulation (risk of OHSS) is a challenging situation. This study describes an OHSS-free protocol, based on the use of recombinant gonadotrophins for stimulation and gonadotrophin-releasing hormone (GnRH) antagonist to prevent premature LH surge. In six patients with a previous history of excessive response, stimulation was started on day 3 of cycle with recombinant FSH. When follicular diameter reached 13−14 mm, a daily injection of GnRH antagonist was added, together with a daily dose of 75 IU of recombinant LH. When the leading follicles reached 17 mm in diameter, ovulation was triggered with a single dose of 0.2 mg triptorelin. Luteal support with vaginal oestradiol and progesterone was started on the day of oocyte retrieval. None of the patients developed clinically significant OHSS. Mean maximal oestradiol concentration was 23,209 pmol/l, and mean number of embryos obtained per patient was 20.5. Fresh embryo transfer resulted in one ongoing pregnancy and two chemical pregnancies. Thaw cycles have resulted so far in two additional ongoing pregnancies. This protocol removes the risk of OHSS and has a good clinical outcome, and therefore merits further research.

Long-term treatment with vaginal estradiol tablets—an impact on uterine artery blood flow

Objective: We investigated, using color Doppler ultrasound, possible detectable blood changes of prolonged treatment with 17-β-estradiol tablets on uterine artery blood flow, in a cohort of low risk postmenopausal women. Methods: 39 postmenopausal women, who were taking local estrogen therapy for at least 6 months, were examined in the study group. Forty-two women who never used hormone replacement therapy consisted a control group. They were examined with color Doppler ultrasound and the pulsatility index of the uterine artery was measured. The groups were divided into three subgroups (the age, the duration of the postmenopause, and the duration of the treatment) and the data were compared among groups and within subgroups. Results: The overall mean age of the patients was 66 years, the mean duration of the postmenopause was 15 years, the overall mean PI was 1.96 ± 0.90, and the mean duration of taking vaginal estradiol tablets was 1.97 years for the study group; and 64 years, 13 years and 2.88 ± 0.96 for the control group, respectively. There was a difference in the mean PI among groups. No significant differences in pulsatility index values in the subgroups were found. Conclusion: Long-term treatments with vaginal estradiol tablets in low risk women causes lowering of the uterine artery PI values compared to the women who are not receiving hormone replacement therapy.

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

Evaluate the efficacy and acceptability of a novel vaginal ring delivering oestradiol acetate (Menoring) versus oral oestradiol for relief of climacteric symptoms in postmenopausal women. Prospective, multicentre, randomised, double-blind, comparator-controlled, parallel group study. Twenty-one centres in the United Kingdom. Postmenopausal women, aged <65 years experiencing > or =20 hot flushes/night sweats per week for two consecutive weeks. Patients received a vaginal ring releasing oestradiol acetate at a rate equivalent to 50 microg/day in addition to placebo tablets (vaginal ring group) or oral oestradiol 1 mg/day in addition to placebo vaginal ring (oral group) for 24 weeks. For patients with inadequate control of vasomotor symptoms, dosage was doubled at 12 weeks. Non-hysterectomised women received norethisterone 1 mg/day for 12 days in each 28 day cycle. Efficacy was assessed by change in climacteric symptoms measured by the Greene Climacteric Scale, as well as mean change in frequency of hot flushes/night sweats. A total of 159 patients were enrolled (84 vaginal ring, 75 oral). Significant improvement (P < 0.05) in mean total Greene Climacteric Scale scores in both treatment groups was observed at 12 and 24 weeks and for every subscale score including anxiety, depression and sexual dysfunction (P < 0.05). In both groups, frequency of hot flushes/night sweats was significantly reduced (P < 0.001) at 12 and 24 weeks. No significant between-group differences were noted at 12 or 24 weeks. The oestradiol vaginal ring significantly improved climacteric symptoms as measured by Greene Climacteric Scale scores and reduced the frequency of hot flushes/night sweats. Efficacy and safety of vaginal ring oestradiol were comparable with those of oral therapy. Patient evaluations of oestradiol vaginal ring tolerability and acceptability were excellent.

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

Objective Evaluate the efficacy and acceptability of a novel vaginal ring delivering oestradiol acetate (Menoring) versus oral oestradiol for relief of climacteric symptoms in postmenopausal women. Design Prospective, multicentre, randomised, double-blind, comparator-controlled, parallel group study. Setting Twenty-one centres in the United Kingdom. Population Postmenopausal women, aged <65 years experiencing ≥20 hot flushes/night sweats per week for two consecutive weeks. Methods Patients received a vaginal ring releasing oestradiol acetate at a rate equivalent to 50 μg/day in addition to placebo tablets (vaginal ring group) or oral oestradiol 1 mg/day in addition to placebo vaginal ring (oral group) for 24 weeks. For patients with inadequate control of vasomotor symptoms, dosage was doubled at 12 weeks. Non-hysterectomised women received norethisterone 1 mg/day for 12 days in each 28 day cycle. Main outcome measures Efficacy was assessed by change in climacteric symptoms measured by the Greene Climacteric Scale, as well as mean change in frequency of hot flushes/night sweats. Results A total of 159 patients were enrolled (84 vaginal ring, 75 oral). Significant improvement ( P < 0.05) in mean total Greene Climacteric Scale scores in both treatment groups was observed at 12 and 24 weeks and for every subscale score including anxiety, depression and sexual dysfunction ( P < 0.05). In both groups, frequency of hot flushes/night sweats was significantly reduced ( P < 0.001) at 12 and 24 weeks. No significant between-group differences were noted at 12 or 24 weeks. Conclusions The oestradiol vaginal ring significantly improved climacteric symptoms as measured by Greene Climacteric Scale scores and reduced the frequency of hot flushes/night sweats. Efficacy and safety of vaginal ring oestradiol were comparable with those of oral therapy. Patient evaluations of oestradiol vaginal ring tolerability and acceptability were excellent.

Vaginal estrogen preparations: a review of safety and efficacy for vaginal atrophy.

A theoretical advantage of local (i.e., vaginal) therapy of genitourinary symptoms could be avoidance of systemic adverse effects. Review of efficacy and adverse effects of commonly prescribed vaginal estrogens is of great clinical relevance. A Medline (1966-present) search was performed for randomized controlled trials involving vaginal estrogens. Reference lists of papers were reviewed for additional references. Twenty-two references were randomized controlled trials of vaginal estrogens used by postmenopausal women with signs or symptoms of vaginal atrophy. Subject numbers ranged from 20 to 251. Duration ranged from 2 weeks to 1 year. Different preparations and schedules were used across the trials. All treatments alleviated signs and symptoms of atrophic vaginitis, regardless of whether objective signs of atrophy were required for study entry. Data for urinary symptoms was conflicting; the ring may prevent recurrent urinary tract infections (UTIs). The trials with endometrial scrutiny were less than one year and had mixed results. Nonhormonal lubricant is effective in improving some atrophic signs and symptoms. All preparations were associated with vaginal irritation. Bleeding with vaginal estradiol tablets may be less than that with CEE cream. Vaginal tablets or rings were preferred over other preparations. There were no serious adverse events reported. There was occasional expulsion of estradiol ring in the setting of prior hysterectomy. All preparations are effective in decreasing signs and symptoms of vaginal atrophy, but they differ slightly in their adverse event profiles. Long-term safety of the preparations is best established for estradiol tablets (1 year), but is lacking for all preparations.

Neither sildenafil nor vaginal estradiol improved endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages

Reduced pregnancy rates (PRs) have been associated with maximum endometrial thickness of ≥8 mm immediately prior to progesterone (P) secretion or supplementation. Some claims have been made that treatment with sildenafil citrate or vaginal estradiol (E2) can improve endometrial thickness in women with poor response to oral E2. The present study randomly assigned women attempting frozen embryo transfer (ET) who failed to attain an 8 mm endometrial thickness following graduating dosages of oral E2 to treatment with oral E2 plus 25 mg 4× per day of sildenafil from day 3 to 9 of cycle (vaginal wash day 10) or oral E2 plus 2 mg 2× per day of vaginal E2 from day 2 to peak thickness. Sixteen patients with a mean number of 1.5 attempted but cancelled frozen ET cycles were selected. The mean endometrial thickness for those cycles following oral E2 treatment was 6.6 mm and was 6.3 mm on cycles immediately prior to the study. Nine patients took sildenafil and the average maximum thickness was 6.4 mm. Seven women randomized to vaginal E2 had a mean endometrial thickness of 7.2 mm. Three of the 9 women first taking sildenafil tried a second cycle with the vaginal E2 regimen and the maximum thickness was 7.3 mm. Six of the 7 women who took vaginal estrogen first tried sildenafil but the maximum thickness attained was 6.8 mm. Frozen ET was attempted in only 6 of the 16 women (4 with sildenafil and 2 with vaginal E2) and only 1 pregnancy (16.6%) was achieved in a woman on the sildenafil treatment. During the same time period the PR at our center for women up to age 45 following frozen ET was 35.0% (n = 513). These data suggest that in general neither the addition of sildenafil therapy nor vaginal E2 improves maximum endometrial thickness. Sildenafil failed to improve the endometrial thickness in 15 of 15 women and vaginal E2 failed in 10 of 10 women. These data do not preclude the possibility that an occasional patient could respond to these treatments. These data are consistent with previous conclusions that thin endometria are associated with a lower PR following ET.

Sequential hormonal supplementation with vaginal estradiol and progesterone gel corrects the effect of clomiphene on the endometrium in oligo-ovulatory women

We investigated the possibility of correcting the endometrial alterations induced with clomiphene citrate (CC) by vaginal hormonal supplementation (HS) with estradiol (E2) and progesterone gel. Oligo-ovulatory women were prospectively randomized into four groups receiving either 50 mg (groups 1 and 2) or 100 mg (groups 3 and 4) of CC from cycle day 3-8. Groups 2 and 4 also received vaginal E2 cream 0.1 mg twice daily from day 8 until the LH surge and vaginal progesterone gel, starting 3 days after ovulation. All participants had an endometrial biopsy performed 10 +/- 1 days after ovulation. All biopsies in the HS groups (2 and 4) showed complete predecidual changes, and were 'in-phase' with findings normally made 10 days post-ovulation (+/- 2 days of clinical dating). However, without HS (groups 1 and 3), only 4/6 and 3/6 biopsies showed predecidual changes in women receiving 50 and 100 mg of CC. The addition of vaginal E2 and progesterone to CC ovulation induction regimens normalizes the alterations in endometrial morphology. Hormonal treatment combining vaginal E2 and progesterone may improve endometrial receptivity in CC cycles and ultimately yield higher pregnancy rates.

Vaginal oestradiol for the treatment of lower urinary tract symptoms in postmenopausal womena double-blind placebo-controlled study

A prospective randomised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency, urgency and/or urge incontinence recruited from a tertiary referral urogynaecology clinic. After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo. This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract.

Hormone Supplementation (Vaginal Estradiol [E 2] and Crinone 8%) Normalizes Delayed Endometrial Development in Clomiphene-Treated Oligo-Ovulatory Women

Objective: Clomiphene citrate (CC) treatment induces ovulation in 50–75% of women with oligo-anovulation, but pregnancy rates (PR) are much lower than predicted. To avoid potential detrimental effects of CC therapy on the endometrium, we investigated the effects of hormone supplementation (HS) on the endometrium in CC-treated oligo-ovulatory women.

Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women

Objective: To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial®). Methods: A 2-year randomised placebo-controlled study of 94 healthy women, 1–3 years after spontaneous menopause, receiving either placebo ( n=23), 1.25 mg/day ( n=36) or 2.5 mg/day ( n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. Results: Fifty-one percent ( n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% ( n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% ( n=5) in the placebo group. The women who bled in the placebo group were younger ( P<0.01), had menopause at an earlier age ( P<0.05), had a shorter duration since menopause ( P<0.05) and had a higher median E2 serum level prior to bleeding ( P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. Conclusions: In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2–2.5 times more likely to present with vaginal bleeding compared with placebo ( P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.

Relationships between vaginal collagen, plasma oestradiol and uterine prolapse in turkeys

Relationships between vaginal collagen, plasma oestradiol and uterine prolapse in turkeys

Biochemical and histological effects of vaginal estriol and estradiol applications on the endometrium, myometrium and vagina of postmenopausal women

Estrogen and progesterone receptors in the cytosol (ERc, PRC) and estrogen receptors in the nuclear compartment (ER11) were measured in the endometrium, myometrium and vagina of 29postmenopausal women who underwent hysterectomy. The effects of vaginal estriol (0.5 mg daily) compared to 17β-estradiol (0.05 mg daily) therapy on these receptor levels were studied. In addition, the endometrium was examined by light microscopy for estrogenic stimulation.We found biochemical and histological signs of estrogenic stimulation in all three tissues after estradiol as well as estriol therapy. In the vagina the effect of both estrogens on the ERc concentration was different from that in the endometrium and myometrium. The effects of estradiol and estriol on the ER11 were comparable in all three tissues. The PRc levels increased significantly in all tissues after estrogen therapy; in the myometrium it was significantly higher after estriol than after estradiol applications.In conclusion, there were no clear differences between vaginal estradiol and estriol medication with regard to the effects on receptor levels in vaginal and uterine tissues. In the histological studies at the light microscopy level similar signs of estrogen stimulation of the endometrium were found following estradiol and estriol medication.

Ultrasonographic and endocrine evaluation of ovarian function among Norplant ® implants users with regular menses

With the objective of evaluating the ovulatory function among long-term Norplant implants users with regular menstrual cycles, we undertook this prospective study including 11 Norplant implants users and 11 control women who were not using hormonal methods of fertility control. Exposed and unexposed women had had at least three regular menstrual cycles preceding enrollment. All women were followed during one menstrual cycle by serial vaginal ultrasound and estradiol (E 2), progesterone (P), LH, and FSH measurements. Three Norplant implants users ovulated, three had luteinization of an unruptured follicle (LUF), three had persistent follicle growth up to a mean of 33 mm without rupture, and two had no follicular development beyond 16 mm. Ten of the controls had normal ovulation and one had LUF. Mean peak LH and FSH among Norplant implants users who ovulated were three- to four-fold lower than among controls. Although users of Norplant implants with regular cycles frequently have luteal activity, the results of this study suggest that elevation of P during the second half of the cycle does not necessarily indicate ovulation has occurred and may frequently be associated with the presence of lureinized unruptured follicle. When ovulation occurs, there are usually abnormal hormone levels (low LH/FSH peak, low progesterone) which may also contribute to the contraceptive effect of Norplant implants.

Oestrogen concentrations in plasma, endometrium, myometrium and vagina of postmenopausal women, and effects of vaginal oestriol (E 3) and oestradiol (E 2) applications

Oestradiol (E2), oestriol (E3) and oestrone (E1) levels were measured in plasma and endometrium, myometrium and vagina of 29 postmenopausal women who underwent hysterectomy. The influence of vaginal E3, compared to vaginal E2 therapy at a dose one-tenth that of E3 on the basal steroid levels was examined. We found (1) no correlation between basal tissue and plasma concentrations of the oestrogens in untreated postmenopausal women, however, after vaginal E3 therapy we did find a positive correlation between them, (2) E2 to be the oestrogen in the highest basal concentration in endometrium and myometrium as well as in the vagina, (3) higher basal concentrations of all three oestrogens in endometrium compared to myometrium and vagina, (4) a long term (at least 12 h) elevation of the plasma and tissue E3 concentrations after vaginal E3 therapy (0.5 mg per day), (5) no significant changes of the plasma and tissue E2 concentrations after 0.05 mg per day vaginal E2 therapy, measured 12 h after the last application and (6) no signs of a difference between vagina and uterus in uptake and retention of E3 or E2. In conclusion, there was no difference on this level of mechanism of action in vagina and uterus which can account for the supposed vaginotrophicity and non-uterotrophicity observed with E3 but not E2.

Oestrogen concentrations in plasma, endometrium, myometrium and vagina of postmenopausal women, and effects of vaginal oestriol (E 3) and oestradiol (E 2) applications

Oestradiol (E 2), oestriol (E 3) and oestrone (E 1) levels were measured in plasma and endometrium, myometrium and vagina of 29 postmenopausal women who underwent hysterectomy. The influence of vaginal E 3, compared to vaginal E 2 therapy at a dose one-tenth that of E 3 on the basal steroid levels was examined. We found (1) no correlation between basal tissue and plasma concentrations of the oestrogens in untreated postmenopausal women, however, after vaginal E 3 therapy we did find a positive correlation between them, (2) E 2 to be the oestrogen in the highest basal concentration in endometrium and myometrium as well as in the vagina, (3) higher basal concentrations of all three oestrogens in endometrium compared to myometrium and vagina, (4) a long term (at least 12 h) elevation of the plasma and tissue E 3 concentrations after vaginal E 3 therapy (0.5 mg per day), (5) no significant changes of the plasma and tissue E 2 concentrations after 0.05 mg per day vaginal E 2 therapy, measured 12 h after the last application and (6) no signs of a difference between vagina and uterus in uptake and retention of E 3 or E 2. In conclusion, there was no difference on this level of mechanism of action in vagina and uterus which can account for the supposed vaginotrophicity and non-uterotrophicity observed with E 3 but not E 2.