Vaginal Estradiol Research Articles

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.

Letter to the Editor

Letter to the Editor

Predisposing Factors and Treatment Outcome of Different Stages of Intrauterine Adhesions

ObjectiveTo evaluate the predisposing factors and treatment outcomes of different stages of intrauterine adhesions. MethodsWe examined the medical records of women with Asherman syndrome seen during the period of January 2000 to December 2007 at two McGill University teaching hospitals in Montreal. Data retrieved included patient’s age, menstrual pattern, fertility, factors related to intrauterine adhesions, and rates of amenorrhea and pregnancy at 12-month follow-up. The diagnosis was established by hysteroscopic examination. After confirmation of the diagnosis, the intrauterine adhesions were removed using a standard technique with a loop electrode and glycine 1.5% as distension medium. In cases with severe intrauterine adhesions, abdominal ultrasound was used to ensure that the uterine cavity was not breached. At the completion of each procedure a number 16 Foley catheter with 5mL of normal saline in the bulb was placed in the uterine cavity and removed five days later. In addition, vaginal estradiol 17β was administered three times daily for four weeks with oral progesterone administered in the fourth week of estradiol treatment. ResultsOf 65 patients, we identified 24 with stage I intrauterine adhesions (36.9%), 30 with stage II (46.2%), and 11 with stage III (16.9%). The main reasons for referral were infertility (stage I 75%, stage II 73.3%, stage III 27.3%), and amenorrhea (stage I 25%, stage II 23.3%, stage III 72.7%). The main predisposing factor was dilatation and curettage. Of 40 patients with intrauterine adhesions related to early pregnancy curettage, 18 patients (45%) had stage I adhesions, 17 (42.5%) had stage II, and five (12.5%) had stage III. This contrasted with 10 patients who had peripartum curettage, in whom six (60%) developed stage III adhesions (P = 0.004). The rate of amenorrhea was 32.3% before adhesiolysis and 9.2% after. Among 43 women who wished to conceive, the pregnancy rate was 51.2% and the live birth rate 32.6%. ConclusionThe main reasons for referral of women with intrauterine adhesions are infertility and amenorrhea. Postpartum curettage leads to severe adhesions. The rates of pregnancy and term pregnancy among this selected group of women were similar regardless of the severity of adhesions.

Juvenile Granulosa and Theca Cell Tumor of the Ovary as a Rare Cause of Precocious Puberty: Case Report and Review of Literature

Background The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case documents a rare cause of peripheral precocious puberty—a juvenile granulosa and theca cell ovarian tumor—and a brief review of the literature for this tumor type. Case A 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Menarche occurred 5 months after thelarche. A thorough workup revealed a large multicystic left ovary. Other causes of precocious puberty were excluded. She underwent an exploratory laparotomy and left salpingo-oophorectomy. Pathology reported a juvenile granulosa and theca cell tumor of the ovary, FIGO stage 1A. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. A literature review found that early stage disease has an excellent prognosis and that adjuvant chemotherapy is not indicated in this setting. Summary and Conclusion Juvenile granulosa and theca cell tumor of the ovary is a rare cause of peripheral precocious puberty, even more so than juvenile granulosa cell tumor, due to the theca component. Treatment is surgical and an excellent prognosis is possible for early stage disease.

The use of oestradiol therapy in postmenopausal women after TVT-O anti-incontinence surgery

Objective To investigate whether patients who were treated with TVT-O procedure for urodynamic stress incontinence had a significant improvement in their urodynamic findings and their post-operative symptoms (frequency, urgency, nocturia) if they were treated post-operatively with vaginal oestradiol for 6 months compared to the non-treated group. Methods Prospective randomised study. 190 patients were asked to participate in our study. Finally, a total of 92 patients in group 1 and 91 patients in group 2 completed the study. In group 1, which was the treatment group, patients having the TVT-O procedure for urodynamic stress incontinence were instructed to use post-operatively oestradiol tablets, 25 micrograms (Vagifem, Novo Nordisk) vaginally, once daily, nocte, for 2 weeks and then twice weekly for 6 months. The patients in group 2 (control group) had the TVT-O procedure only. All patients were reviewed in 2 months and again in 6 months time. Results There was no statistically significant difference between the two groups concerning pre-operative and post-operative haemoglobin, operative time, hospital stay or return to work. The within group analysis did not show significant differences between pre-operative and post-operative urodynamic data in both groups. Patients treated with vaginal estradiol post-operatively showed a statistically significant reduction in relation to the symptoms of urgency and frequency but not in relation to nocturia and urge incontinence compared to the non-treated group. There is no difference in relation to the efficacy of TVT-O procedure between the groups at 6 months follow-up. Conclusion It appears that vaginal oestradiol treatment could be offered to postmenopausal patients after a TVT-O procedure having the symptoms of frequency and urgency provided they are aware of the lack of evidence regarding long term benefit.

A combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomised controlled trial

ObjectiveTo compare the impact of 1000 μg of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after 2 weeks of pretreatment with estradiol vaginal tablets in postmenopausal women prior to day-care operative hysteroscopy.DesignRandomised, double-blind, placebo-controlled sequential trial.SettingNorwegian university teaching hospital.PopulationSixty-seven postmenopausal women referred for day-care operative hysteroscopy.MethodsThe women were randomised to receive either 1000 μg of self-administered vaginal misoprostol or self-administered vaginal placebo on the evening before day-care operative hysteroscopy. All women had administered a 25-μg vaginal estradiol tablet daily for 14 days prior to the operation.Main outcome measuresPrimary outcome: preoperative cervical dilatation at hysteroscopy. Secondary outcomes: difference in dilatation at recruitment and before hysteroscopy, number of women who achieved a preoperative cervical dilatation of 5 mm or more, acceptability, complications and adverse effects.ResultsThe mean cervical dilatation was 5.7 mm (SD, 1.6 mm) in the misoprostol group and 4.7 mm (SD, 1.5 mm) in the placebo group, the mean difference in cervical dilatation being 1.0 mm (95% CI, 0.2–1.7 mm). Self-administered vaginal misoprostol of 1000 μg at home on the evening before day-care hysteroscopy is safe and highly acceptable, although a small proportion of women experienced lower abdominal pain.ConclusionsOne thousand micrograms of self-administered vaginal misoprostol, 12 hours prior to day-care hysteroscopy, after 14 days of pretreatment with vaginal estradiol, has a significant cervical ripening effect compared with placebo in postmenopausal women.

Menopause Leading to Increased Vaginal Wall Thickness in Women with Genital Prolapse: Impact on Sexual Response

Hypoestrogenism causes structural changes in the vaginal wall that can lead to sexual dysfunction. A reduction in vaginal wall thickness has been reported to occur after menopause, although without precise morphometry. To measure vaginal wall thickness in women with genital prolapse in normal and hypoestrogenic conditions and to correlate sexual dysfunction with vaginal wall thickness and estradiol levels. Surgical vaginal specimens from 18 normoestrogenic and 13 postmenopausal women submitted to surgery for genital prolapse grades I and II were examined. Patients were evaluated for FSH, estradiol, prolactin, glycemia, and serum TSH levels. For histological analysis, samples were stained with Masson's trichrome and hematoxylin-eosin. Sexual function was assessed by the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). GRISS questionnaire, histological analysis, morphometric methods, Masson's trichrome. The vaginal wall was thicker in the postmenopausal than premenopausal group (2.72 +/- 0.72 mm and 2.16 +/- 0.43, P = 0.01, and 2.63 +/- 0.71 mm and 2.07 +/- 0.49 mm, P = 0.01, for the anterior and posterior walls, respectively). These thicknesses seem to be due to the muscular layer, which was also thicker in the postmenopausal group (1.54 +/- 0.44 and 1.09 +/- 0.3 mm, P = 0.02, and 1.45 +/- 0.47 and 1.07 +/- 0.44 mm, P = 0.03, for the anterior and posterior wall, respectively). The vaginal epithelium was thinner in the middle segment than in the proximal one in the posterior wall (0.17 +/- 0.07 mm, 0.15 +/- 0.05 mm, 0.24 +/- 0.09 mm, P = 0.02). There was no correlation between coital pain, vaginal wall thickness, and estradiol levels in either group. The vaginal wall is thicker after menopause in women with genital prolapse. In this study, vaginal thickness and estrogen levels were not related to sexual dysfunction.

O100 An open-label randomised trial to determine the most effective regimen of vaginal estrogen to reduce the prevalence of atrophic changes reported in postmenopausal cervical smears

Objective: Atrophic Papanicolaou (Pap) smears from postmenopausal women may be unsatisfactory for assessment or result in a false-positive diagnosis of a cytological abnormality. We investigated the effect of vaginal estrogen treatment before the Pap test on the odds of an atrophic smear. Methods: An open-label randomized controlled trial was conducted to compare the proportion of atrophic Pap smears from postmenopausal women assigned to either (1) a regimen of one 25-Kg vaginal estradiol tablet inserted nightly for five nights before their Pap test, (2) a single 25-Kg vaginal estradiol tablet before the test, or (3 )a control group with no previous estrogen administration. All smears were reread and classified as atrophic or nonatrophic at the conclusion of the study by a single cytopathologist who was blinded to the study arms. Results: One hundred fifty-four (94%) of the 164 postmenopausal women who consented to the study were included in the final analysis. Fifty-one women had received the five-night course of tablets, 50 had received one tablet, and 53 were assigned to the group with no previous estrogen use. The odds of an atrophic smear were significantly lower in women who used the five-night estrogen regimen than in women who did not use estrogen. The estimated odds ratio of an atrophic smear in the five-night regimen was 0.01 (95% CI, 0.03-0.26) compared with the no-estrogen control group. Moreover, using one tablet of estrogen had no significant effect on the likelihood of an atrophic smear compared with using none. The odds ratio of an atrophic smear in the single estrogen tablet group was 1.05 (95% CI, 0.48-2.29) compared with the no-estrogen group. Conclusions: The odds of an atrophic smear are significantly reduced for postmenopausal women who use a

The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that operates as sensor of cellular energy status and effector for its coupling to cell growth and proliferation. At the hypothalamic arcuate nucleus, mTOR signaling has been recently proposed as transducer for leptin effects on energy homeostasis and food intake. However, whether central mTOR also participates in metabolic regulation of fertility remains unexplored. We provide herein evidence for the involvement of mTOR in the control of puberty onset and LH secretion, likely via modulation of hypothalamic expression of Kiss1. Acute activation of mTOR by l-leucine stimulated LH secretion in pubertal female rats, whereas chronic l-leucine infusion partially rescued the state of hypogonadotropism induced by food restriction. Conversely, blockade of central mTOR signaling by rapamycin caused inhibition of the gonadotropic axis at puberty, with significantly delayed vaginal opening, decreased LH and estradiol levels, and ovarian and uterine atrophy. Inactivation of mTOR also blunted the positive effects of leptin on puberty onset in food-restricted females. Yet the GnRH/LH system retained their ability to respond to ovariectomy and kisspeptin-10 after sustained blockade of mTOR, ruling out the possibility of unspecific disruption of GnRH function by rapamycin. Finally, mTOR inactivation evoked a significant decrease of Kiss1 expression at the hypothalamus, with dramatic suppression of Kiss1 mRNA levels at the arcuate nucleus. Altogether our results unveil the role of central mTOR signaling in the control of puberty onset and gonadotropin secretion, a phenomenon that involves the regulation of Kiss1 and may contribute to the functional coupling between energy balance and gonadal activation and function.

An open-label randomized trial to determine the most effective regimen of vaginal estrogen to reduce the prevalence of atrophic changes reported in postmenopausal cervical smears

Atrophic Papanicolaou (Pap) smears from postmenopausal women may be unsatisfactory for assessment or result in a false-positive diagnosis of a cytological abnormality. We investigated the effect of vaginal estrogen treatment before the Pap test on the odds of an atrophic smear. An open-label randomized controlled trial was conducted to compare the proportion of atrophic Pap smears from postmenopausal women assigned to either (1) a regimen of one 25-microg vaginal estradiol tablet inserted nightly for five nights before their Pap test, (2) a single 25-microg vaginal estradiol tablet before the test, or (3) a control group with no previous estrogen administration. All smears were reread and classified as atrophic or nonatrophic at the conclusion of the study by a single cytopathologist who was blinded to the study arms. One hundred fifty-four (94%) of the 164 postmenopausal women who consented to the study were included in the final analysis. Fifty-one women had received the five-night course of tablets, 50 had received one tablet, and 53 were assigned to the group with no previous estrogen use. The odds of an atrophic smear were significantly lower in women who used the five-night estrogen regimen than in women who did not use estrogen. The estimated odds ratio of an atrophic smear in the five-night regimen was 0.01 (95% CI, 0.03-0.26) compared with the no-estrogen control group. Moreover, using one tablet of estrogen had no significant effect on the likelihood of an atrophic smear compared with using none. The odds ratio of an atrophic smear in the single estrogen tablet group was 1.05 (95% CI, 0.48-2.29) compared with the no-estrogen group. The odds of an atrophic smear are significantly reduced for postmenopausal women who use a five-night regimen of vaginal estrogen before their Pap test.

Receptor Isoforms That Mediate Estrogen and Progestagen Action in the Female Lower Urinary Tract

Bladder symptoms can be ameliorated by sex steroids but to our knowledge the mechanism of action is unknown. Previous studies of steroid receptor expression in the bladder did not indicate receptor subtype expression. We report the distribution of estrogen and progesterone receptor isoforms in the female lower urinary tract. Prospectively recruited women undergoing routine urogynecological or gynecological surgery provided cold cup biopsy samples from the bladder dome, trigone, and proximal and distal urethra. The samples were immediately frozen or fixed in formalin. After RNA extraction transcripts for estrogen receptor alpha and beta, and progesterone receptor A and B were noted on reverse transcriptase-polymerase chain reaction using isoform specific primers. The precise cellular localization of receptor proteins and their relative levels were assessed by immunochemistry in formalin fixed tissue sections with isoform specific antibodies. Nine premenopausal and 10 postmenopausal women were recruited into the study. Two postmenopausal women on hormone replacement therapy. Estrogen receptor alpha and beta, and progesterone receptor A and B transcripts were detected in whole bladder extracts. Nuclear estrogen receptor alpha immunoreactivity was present in squamous epithelium but absent from transitional epithelium. Estrogen receptor beta immunoreactivity was expressed in squamous and transitional cell epithelium. Nuclear progesterone receptor expression was present in urethral squamous epithelium only. Progesterone receptor expression was greater in premenopausal women and in postmenopausal women on estrogen. Estrogen receptor alpha and beta genes are transcribed in bladder tissue but only estrogen receptor beta is translated into protein, suggesting that the urothelium responds to endogenous estrogen via estrogen receptor beta. Progesterone receptor expression is confined to urethral squamous epithelium and the major isoform is progesterone receptor A.

Blastocyst development rate impacts outcome in cryopreserved blastocyst transfer cycles

To assess cycle outcome among day 5 and day 6 cryopreserved frozen-thawed blastocyst embryo transfers (FBET). Retrospective cohort study. Military-based assisted reproduction technology (ART) center. One hundred seventy-two nondonor, programmed cryopreserved embryo cycles. Fully expanded blastocysts on day 5 were cryopreserved on day 5, and those achieving this state on day 6 were cryopreserved on day 6. Leuprolide acetate was given for ovulation inhibition, and endometrial supplementation was by oral and vaginal estradiol. Progesterone in oil was administered, and blastocyst transfer occurred in the morning of the sixth day of progesterone. Implantation, pregnancy, and live-birth rates. Fresh and frozen cycle characteristics were similar between groups. Day-5 FBET had statistically significantly higher implantation rates (32.2% vs. 19.2%), which remained significant even when adjusting for covariates (odds ratio: 1.91; 95% confidence interval, 1.00, 3.67). Live-birth rates trended toward improvement after adjusting for covariates (odds ratio: 1.18; 95% confidence interval, 0.61, 2.30). Cryopreserved day-5 blastocysts have higher implantation rates and trend toward improved pregnancy outcomes compared with cryopreserved day-6 blastocysts. This suggests that embryo development rate may, in part, predict implantation and subsequent FBET outcomes, although embryos not achieving the blastocyst stage until day 6 still demonstrate acceptable outcomes.

Comparison of the Effects of Hormone Therapy Regimens, Oral and Vaginal Estradiol, Estradiol + Drospirenone and Tibolone, on Sexual Function in Healthy Postmenopausal Women

Sexual dysfunction is more prevalent in postmenopausal women. To prospectively evaluate and compare the effects of hormone therapy (HT) regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. The study included 169 consecutive healthy postmenopausal women, and the women were divided into two groups: 111 women received HT, and 58 women received no treatment and served as a control group. As an HT, 23 women with surgically induced menopause received oral 17-beta estradiol. The rest of the women with natural menopause were prospectively randomized: 22 received oral 17-beta estradiol + drospirenone daily, 42 received oral tibolone, and 24 received vaginal 17-beta estradiol. Sexual function was evaluated with a detailed 19-item questionnaire, the female sexual function index, including sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The differences in sexual function were compared before and 6 months after the treatment in all women. Total sexual function score increased from 19.81 +/- 7.15 to 22.9 +/- 6.44 in the HT group and decreased from 21.6 +/- 8.69 to 17.6 +/- 5.7 in the control group, revealing a significant difference from baseline to post-treatment between the two groups (P = 0.000). The highest improvement in total score and arousal was achieved with the oral 17-beta estradiol (P = 0.000 and P = 0.000, respectively). The highest improvement in lubrication was achieved with the oral and vaginal 17-beta estradiol groups (P = 0.000). The highest improvement in orgasm was achieved with the tibolone group (P = 0.000). The highest improvement in pain was achieved with the oral and vaginal 17-beta estradiol groups (P = 0.000). HT provided significant improvement in sexual function compared to women receiving no treatment, and therefore, HT regimens should be suggested for improvement in sexual functioning of postmenopausal women.

A case series of patients with endometrial insufficiency treated with pentoxifylline and alpha-tocopherol

To determine the effect of pentoxifylline (PTX) and alpha-tocopherol (Vitamin E) on endometrial parameters in women with persistent thin and unfavorable uterine linings. Case series. 8 patients (11 cycles) were identified with unfavorable endometrial lining by thickness ≤6 mm or echogenicity type ≥2 in late follicular phase. These parameters were unresponsive to high dose oral & vaginal estradiol (E2) therapy. Patients were treated with oral PTX 400 mg twice/day and vitamin E 400 IU twice/day with a goal of 6 months treatment. Outcome measures: endometrial thickness, echogenicity type and pregnancy. Table 1 summarizes our results. Tabled 1Table.PatientHistoryUterine lining (mm) Pre-PTX/Vit ETreatment Duration (months)Lining Thickness (mm)/TypePregnancy Outcome1a34 y/o G1P0; Asherman's 2° to retained products of conception (POC)5 type 2–396.5 type 3Spont preg; missed AB1bSame5 type 2Restarted for 110 type 3No preg2a37 y/o G1P1; idiopathic endometrial insufficiency5 type 225 type 1Biochemical preg2bSame5 type 246 type 2FET; Live birth339 y/o G1P1; Asherman's 2° to post-partum hemorrhage6.5 type 2106.5 type 1–2No preg but improved cavity4a32 y/o G1P0; acute & chronic endometritis, scarred endometrium on hysteroscopy 2° to retained POC. Gestational carrier recommended5.5 type 2–311N/ASpont preg; live birth4b34 y/o; retained placenta after second delivery6 type 256 type 2FET; live birth534 y/o G0; idiopathic endometrial insufficiency2–6 type 2–32N/ASpont ongoing preg639 y/o G0; idiopathic endometrial insufficiency5.5 type 255–6 type 2Donor egg; no preg739 y/o G3P2; fibroids, cervical stenosis, and Asherman's 2° to hysteroscopic resection of fibroids2–6 type 1–345–7 type 2–3No preg; multiple cycles839 y/o G1P0; unexplained infertility4–8 type 286–8 type 2Spont biochemical preg Open table in a new tab In our case series, PTX and Vitamin E were used for patients who failed to develop an adequate uterine lining. 64% (7/11) of cycles resulted in a pregnancy. The combination of PTX and Vitamin E has been reported to improve endometrial parameters in radiation induced and idiopathic endometrial insufficiency (Ledee-Bataille, Hum Reprod 2002; Letur-Konirsch, F&S 2002). It has been speculated by these authors that increased platelet flexibility & decreased aggregation improves blood flow to small capillaries in the endometrium. Our case series corroborates these findings. This regimen, with minimal risks, provides a potential avenue for endometrial insufficiency.

The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study

To determine whether the use of luteal phase vaginal E(2) supplementation improves clinical pregnancy rates in patients undergoing IVF treatment. Prospective randomized controlled trial. University-based tertiary fertility center. One hundred sixty-six patients undergoing their first cycle of IVF treatment. Patients underwent three different protocols for controlled ovarian hyperstimulation for IVF treatment with long GnRH agonist suppression, use of GnRH antagonist, or a microdose GnRH agonist protocol. Luteal phase support was in the form of IM P. Patients randomized into the study group (n = 84) received E(2) supplementation in the form of vaginal estrace 2 mg twice a day starting on the day of ET. Patients randomized to the control group (n = 82) received no E(2) supplementation. Clinical pregnancy rates. There were no significant differences in the implantation (56/210 [26.7%] vs. 64/203 [31.5%]), clinical pregnancy (42/84 [50%] vs. 52/82 [63.4%]), and ongoing pregnancy rates (40/84 [47.6%] vs. 46/82 [56.1%]) between the study and control groups, respectively. In the subgroup of patients who used the long GnRH agonist suppression protocol, there was a lower clinical pregnancy rate in the study group compared with the control group (27/55 [49.1%] vs. 42/59 [71.2%]). There were, however, no differences in clinical pregnancy rates between the two groups in patients who used either the GnRH antagonist or microdose GnRH agonist protocols. The addition of vaginal E(2) supplementation to routine P supplementation for luteal support does not improve the probability of conception after IVF treatment.

High-Resolution Ultrasonography of Xenografted Domestic Cat Ovarian Cortex

Transplantation of ovarian tissue has high potential for female gamete conservation. However, optimal timing of oocyte recovery for in vitro maturation and fertilization is still critical. Therefore the aim of the present study was to use high-resolution transcutaneous ultrasonography to monitor follicular development within xenografted ovarian tissue. Ovarian cortex fragments (n=44) from domestic cats were transplanted into athymic nude rats (n=12). Graft development in the animals was assessed weekly by high frequency ultrasound (10-22 MHz) under two different FSH regimes. Blood collection for serum estradiol determination and vaginal smears were performed simultaneously. The xenografts were removed at different time points according to the ultrasound findings. The survival rate of the transplants 4 weeks after surgery was 54.5% and antral follicular growth was observed within 10 grafts from 5 different hosts (8.6 +/- 6.43 follicles per graft). Early follicle antrums could be detected from 0.4 mm onwards. The growth rate of the antral cavity was calculated from weekly measurements (0.56 +/- 0.44 mm per week). Although vaginal cells and estradiol levels followed a cyclic pattern, no correlation was found between follicular diameter, estradiol and keratinized vaginal cells. We recovered 5, 1 and 4 cumulus oocyte complexes from three different individuals during weeks 19, 21, and 23 respectively. Extrusion of a polar body (1 oocyte) and germinal vesicle break down (7 oocytes) indicated progression of maturation after in vitro culture. We conclude that ultrasonography und provided a reliable method to examine xenograft survival and follicular development within the grafts. Furthermore, this technique is suitable for assessment of the efficiency of hormonal treatment and narrowing of the optimal time frame for oocyte retrieval. To our knowledge, this is the first report of the in vivo development of early antral follicles in mammalian species.

PIH16 TREATMENT DURATION FOR ATROPHIC VAGINITIS: CLINICAL TRIALS VERSUS “THE REAL WORLD”

Presented at ISPOR 9th Annual European Congress, Copenhagen, Denmark, October 28-31, 2006 • Atrophic vaginitis affects as many as 15% of premenopausal women, 1040% of postmenopausal women, and 10-25% of women on systemic hormone therapy.1 • Hormone replacement therapy is the most common treatment strategy, as depletion of estrogen levels is considered to be the primary cause of atrophic vaginitis.2 • There are multiple modes of vaginal estrogen delivery: vaginallyadministered topical creams (VC), vaginal estradiol tablets (VT) [Vagifem®, Novo Nordisk A/S], and vaginal rings. • Vaginal creams are more commonly used and have been available for over 50 years, but disadvantages include messiness and application timing.3 • Vaginal tablets are new and less common, but advantages include convenience of timing and mode of administration. • Duration of atrophic vaginitis treatment may vary due to a number of potential reasons including symptom relief, non-adherence to treatment, and disadvantages associated with medication. However, no study has examined the treatment duration associated with atrophic vaginitis in “real-world” clinical practice.

Usage trends of minimally absorbed vaginal estrogens in breast cancer patients versus patients with non-breast malignancies

10620 Background: To determine if differences exist in the use of minimally absorbed vaginal estrogens in a breast cancer population versus one with non-breast malignancies. Methods: A retrospective review of all patients with documented malignancy who were prescribed vaginal 17-β-estradiol tablets (Vagifem, Novo-Disc, Princeton, New Jersey) through the General Gynecology Service from July 1, 2003 to June 30, 2004. Data were accessed from the pharmacy health information computerized system. All patients complained of dyspareunia, and examination was consistent with vaginal atrophy. Comparison between groups was performed using the Fisher Exact Test and t-test. Results: 152 patients were identified_81 patients with breast cancer diagnoses and 71 with non-breast malignancies. There was no difference in the mean age of patients in either group, 56.9 vs. 55.1 years. (p = 0.30). Overall, 60 of the 152 patients refilled their prescriptions through the time of last follow-up. There was no difference in the proportion of breast versus non-breast cancer patients who continued vaginal estradiol, 39.5% (32/81) versus 39.4% (28/71) respectively. When the cohorts were stratified by age ≤ 50 or &gt;50 at the time of initial consultation, 79% (11/14) of breast cancer patients age ≤ 50 years refilled their prescriptions at follow-up compared to 31.3% (21/67) of patients &gt;50 (p = 0.002). In women with non-breast malignancies there was no age-related difference in the proportion who obtained refills: 35% (7/20) ≤ 50 years versus 41.2 % (21/51) &gt;50 years (p = 0.79). Conclusions: Minimally absorbed vaginal estrogens appear to be viewed favorably amongst the younger breast cancer patient population. The older breast cancer population does not appear to continue vaginal estradiol use long-term. This may be due to differences in relationship status, interval from menopause to diagnosis, prior exposure to estrogen, or relief of symptoms with alternative therapies. These findings are different than those observed for similar patients with non-breast malignancies. Further studies looking at the use of minimally absorbed vaginal estrogens are needed to further evaluate the usage trends in differing patient populations. No significant financial relationships to disclose.

Aromatase inhibitor estrogen suppression is reversed by vaginal estradiol

Aromatase inhibitor estrogen suppression is reversed by vaginal estradiol

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors

Background: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer.Patients and methods: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7–10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women.Results: Serum estradiol levels rose from baseline levels ≤5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to <35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women.Conclusions: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.