Ultralow 0.03 mg vaginal estriol in postmenopausal women who underwent surgical treatment for stress urinary incontinence: effects on quality of life and sexual function.

OBJECTIVE: To evaluate the efficacy of low-dose, intravaginal estriol ovules in postmenopausal women with stress urinary incontinence (SUI) before and after transobturator tape (TOT) placement, assessing vaginal health, quality of life (QoL), and sexual function. METHODS: Ninety-six postmenopausal women affected by SUI and scheduled for TOT placement were enrolled. Women were randomized and divided into two groups through 1:1 at baseline (T0): study group (group A, n = 48) and control group (group B, n = 48). Group A was treated daily for 16 weeks with an intravaginal ovule containing 0.03 mg estriol. Vaginal epithelium maturation, QoL, and sexual function were investigated by using the Vaginal Maturation Index (VMI), Short Form-36 (SF-36) questionnaire, and Female Sexual Function Index (FSFI) questionnaire at baseline (T0), before surgery (T1), and 8 weeks after surgery (T2), respectively. RESULTS: Thirty-six women from group A and 44 women from group B completed the study. The VMI improved in group A at T1 (T1 [43.1] vs T0 [38.1]; P = 0.04) and T2 (T2 [47.8] vs T0 [38.1]; P = 0.001). The physical index score of the QoL improved only after surgery in group A (T2 [49.4] vs T0 [39.7]; P = 0.001). On the contrary, the mental index score improved at T1 [T1 (41.9) vs T0 (37.9), (P = 0.02)] and at T2 [T2 (49.6) vs T0 (37.9), P = 0.001]. Group B had improvement of the physical (45.6 vs 39.4; P = 0.001) and mental (43.6 vs 38.9; P = 0.002) index scores at T2. Sexual function improved in group A at T1 (13.9 vs 18.6; P = 0.001) and at T2 (13.9 vs 25.2; P = 0.001), and in group B at T2 (14 vs 17.2; P = 0.001). Moreover, it improved after TOT placement more in group A than in group B (P = 0.001). CONCLUSIONS: Ultralow-dose topical vaginal ovules containing 0.03 mg estriol administrated before and after TOT placement could improve the vaginal epithelium maturation of postmenopausal women affected by SUI. Moreover, vaginal estriol ovules also improved the surgical outcome investigated by SF-36 and FSFI.

Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.

INTRODUCTION: The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. MATERIAL AND METHODS: This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. RESULTS: A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. CONCLUSIONS: Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.

A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause.

OBJECTIVE: We updated a systematic review to evaluate the totality of evidence available for the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause (GSM) based on published randomized controlled trials. METHODS: We searched the Cochrane Library, Ovid, PubMed, Medline, Embase, and Clinicaltrials.gov for English-language articles from database inception to June 2018. Our search consolidated 2,086 potential sources to 53 full-text articles that were reviewed and found relevant to our systematic review. RESULTS: We identified 53 studies that met the inclusion criteria that evaluated the efficacy and safety of vaginal estrogen versus placebo or other hormone and nonhormone controls. Compared with placebo, all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM, whereas some trials demonstrated superiority versus placebo in urogenital symptoms. No significant difference was observed between various dosages and dosage forms of vaginal estrogen products. Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints. Unopposed vaginal estrogens seemed safe, although studies were not powered to detect a long-term estrogenic side effect. CONCLUSION: Estrogen products were found to be clinically effective for the treatment of GSM with doses as low as 4 µg. Vaginal estrogen products seem to be safe with few adverse effects, although there is a lack of long-term controlled clinical trial safety data. This review supports the use of commercially available vaginal estrogen therapies as an effective and safe first-line therapy for the treatment of moderate-to-severe GSM.

Permeation Efficacy of a Transdermal Vehicle with Steroidal Hormones and Nonsteroidal Anti-inflammatory Agents as Model Drugs.

BACKGROUND: Transdermal delivery is an alternative route for the administration of drugs. However, it requires the development of vehicles that allow the drugs to cross the layers of the skin and reach the systemic circulation. OBJECTIVE: In this study, a new transdermal vehicle was evaluated using progesterone, estradiol, estradiol + estriol (Biest) and ketoprofen administered as model drugs. METHODS: To evaluate the ex vivo permeation of the drugs, the Franz vertical diffusion cell with human skin was used. RESULTS: After 24 h, the vehicle was able to deliver 18.32 µg/cm2 of progesterone and 92.07 µg/cm2 of ketoprofen through the skin to the receptor medium. The permeation percentages were 91%, 78.8%, 48.5%, 73.2%, and 63.6%, respectively, for estradiol, estradiol (Biest), estriol (Biest), progesterone and ketoprofen. For all drugs, sufficient amounts were delivered to achieve a systemic effect, and it was also possible to decrease the amount of emulsion applied. CONCLUSION: Thus, the vehicle demonstrated a high performance and the possibility of it being used for drugs that present difficulties in regards to administration by the transdermal route.

Effect on endometrial histology and pharmacokinetics of different dose regimens of progesterone vaginal pessaries, in comparison with progesterone vaginal gel and placebo.

STUDY QUESTION: Which progesterone vaginal pessary dose regimen induces adequate secretory transformation of the endometrium, in comparison with progesterone vaginal gel and placebo? SUMMARY ANSWER: The best secretory transformation of the endometrium was observed during treatment with 400 mg progesterone vaginal pessaries, administered twice daily. WHAT IS KNOWN ALREADY: Vaginally administered progesterone is widely used for luteal phase support (LPS) in assisted reproductive techniques (ART). Although several vaginal formulations using various doses are available, little is known on the impact of formulation and doses at the endometrial level. STUDY DESIGN, SIZE, DURATION: The study had a randomised, observer-blind design and comprised two parts. The participants used study medication during two or three treatment periods, separated by washout periods. Subjects in Part 1 (n = 61 treated) received 200 mg progesterone vaginal pessaries twice daily (bid), 400 mg pessaries bid and the comparator 90 mg progesterone vaginal gel once daily (od) in a 3-way crossover design. Subjects in Part 2 (n = 64 treated) received 100 mg pessaries bid in one period and 400 mg pessaries od in the other period in a 2-way crossover design. A subgroup of these subjects (n = 22 treated) received placebo vaginal pessaries bid in a third period in a non-randomised manner. The study was performed from May 2012 until April 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed at a clinical research centre in healthy female volunteers of reproductive age. The subjects used 2 mg estradiol bid for 24 days in each treatment cycle. Progesterone or placebo was administered vaginally from Day 15 onwards during 10 days. In each treatment period, an endometrial biopsy for histological evaluation was performed on Day 23 and pharmacokinetic parameters were determined after the first progesterone dose on Day 15 and after the last dose on Day 24. MAIN RESULTS AND THE ROLE OF CHANCE: Frequencies of (early and late) secretory transformation of the endometrium, i.e. adequate responses, during treatment with 200 mg and 400 mg vaginal pessaries bid were comparable with those during 90 mg vaginal gel treatment (90-94%), whereas lower secretory transformation rates were observed during treatment with 100 mg bid and 400 mg od (64-75%). At the time of the endometrial biopsy in the cycle the late secretory state of the endometrium, which is characteristic of adequate luteal support, was observed more often with 400 mg pessaries bid (90%) than with vaginal gel (82%) and with lower pessary doses (64-78%). Pharmacokinetic parameters after repeated dosing of vaginal pessaries showed a dose-dependent, but not dose-proportional, increase of plasma progesterone levels. The lowest incidence of bleeding and spotting was reported during treatment with 400 mg pessaries bid. LIMITATIONS REASONS FOR CAUTION: The primary outcome parameter, rate of secretory transformation of the endometrium, is a surrogate for endometrial receptivity and for the actual clinical efficacy. WIDER IMPLICATIONS OF THE FINDINGS: Delivery of progestesterone through 400 mg pessaries bid is an effective alternative method for luteal support in ART. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Actavis Group PTC ehf., Iceland, part of Teva Pharmaceuticals, and L.D. Collins. I.D. and C.K. are directors of Dinox, a contract research organisation. I.K. is Managing Director of Pharmaplex and M.W. is Managing Director of M.A.R.C.O., service organisations involved in organisation/supervision and evaluation/reporting of clinical trials. All received funding for the conduct of the study from Actavis. S.H. and Th.M. are employees of Actavis. TRIAL REGISTRATION NUMBER: EudraCT number 2012-001726-95.

Establishing a Rationale for Compounding Hormone Replacement Therapy.

Why compound bioidentical hormones? Are there no similar commercial products? What is unique about the options compounding pharmacists offer compared with what is out in the marketplace? These are questions that physicians and other practitioners are asking, and it is very important that we have intelligent, well-thought answers when we respond. Times have changed, and the challenges we face today in marketing our compounded therapies are not the same as those of twenty years ago. Premarin is no longer at the top of the heap, and there are topical, commercial products that contain bioidentical estradiol, and capsules that contain the same progesterone that we use. Our compounding advantage comes from our abilities to prepare unique patient-specific products, and, very importantly, from our growing understanding of hormone receptors; we now know there are two main estrogen receptors, 1) estrogen receptor alpha and 2) estrogen receptor beta, and the growing knowledge base associated with the discovery of estrogen receptor beta is quite significant.

Medical treatment of epistaxis in hereditary hemorrhagic telangiectasia: an evidence-based review.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder resulting in vascular dysplasia and formation of arteriovenous malformations. Recurrent epistaxis is a hallmark of the disease. An array of medical therapies are used in this patient population, but robust evidence-based recommendations regarding the medical treatment of epistaxis are lacking. This systematic review was performed to look at the current literature and make meaningful evidence-based recommendations. METHODS: A search of the Ovid MEDLINE, Embase, and Cochrane databases was conducted by a research librarian. Abstracts in the English language and published in a peer-review journal were reviewed for relevance and inclusion. PRISMA guidelines were followed. RESULTS: Eighteen studies met the inclusion criteria. In a few small studies, thalidomide was shown to consistently improve severity and frequency of epistaxis and improve hemoglobin concentrations while decreasing the need for transfusion. Tranexamic acid appeared to only impact the epistaxis severity score and not other clinical outcomes. Selective estrogen modulators (SERMs), propranolol, rose geranium oil, and N-acetylcysteine, have demonstrated promising efficacy in small trials. CONCLUSION: Appropriate medical therapies for epistaxis outcomes in HHT remain undefined, and there is no "gold standard." Many of the studies are small and the data reported are heterogeneous, and therefore the ability to make strong evidence-based recommendations is limited. However, many different medications appear to be promising options.

Does vaginal estriol make urodynamic changes in women with overactive bladder syndrome and genitourinary syndrome of menopause?

OBJECTIVES: OAB is a common finding in postmenopausal women. Hypoestrogenism is the root cause of many signs and symptoms of Genitourinary Syndrome of Menopause (vaginal dryness, atrophy, dyspareunia, urinary disorders, etc.). As such the aim of this study was to evaluate the urodynamic effects of ultralowdose estriol vaginal gel formulation to treat women with Genitourinary Syndrome of Menopause and Overactive Bladder Syndrome. STUDY DESIGN: This open-labeled, single center, prospective study involved 37 women with OAB recruited in our Urogynecological Unit between January and July 2016. They received estriol 50 mcg/g vaginal gel, one applicator-dose per day for 3 weeks followed by one dose twice a week for 12 weeks. Objective and subjective parameters were evaluated before and after treatment through the urodynamic examination, Overactive Bladder symptom score and Short Form Health Survey-36 questionnaires. RESULTS: Vaginal atrophy symptoms and signs as well as the overactive bladder subjective symptom parameter improved significantly. Urodynamic evaluation showed significant improvement in first desire to void and maximum cystometric capacity after estriol usage. Patients who had detrusor overactivity did not show any improvement for this parameter after treatment. The voiding function parameters did not significantly change. Short form-36 showed a better quality of life after treatment especially for the emotional role, as well as mental and general health. CONCLUSIONS: A local ultra-low dose concentration of estriol could be effective in women with vaginal atrophy and Overactive Bladder Syndrome for improving both subjective symptoms and urodynamic parameters of storage function not affecting voiding function.

Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women.

OBJECTIVE: The aim of the study was to evaluate efficacy of fractional CO2 vaginal laser treatment (Laser, L) and compare it to local estrogen therapy (Estriol, E) and the combination of both treatments (Laser + Estriol, LE) in the treatment of vulvovaginal atrophy (VVA). METHODS: A total of 45 postmenopausal women meeting inclusion criteria were randomized in L, E, or LE groups. Assessments at baseline, 8 and 20 weeks, were conducted using Vaginal Health Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and burning), Female Sexual Function Index, and maturation value (MV) of Meisels. RESULTS: Forty-five women were included and 3 women were lost to follow-up. VHI average score was significantly higher at weeks 8 and 20 in all study arms. At week 20, the LE arm also showed incremental improvement of VHI score (P = 0.01). L and LE groups showed a significant improvement of dyspareunia, burning, and dryness, and the E arm only of dryness (P < 0.001). LE group presented significant improvement of total Female Sex Function Index (FSFI) score (P = 0.02) and individual domains of pain, desire, and lubrication. In contrast, the L group showed significant worsening of pain domain in FSFI (P = 0.04), but FSFI total scores were comparable in all treatment arms at week 20. CONCLUSIONS: CO2 vaginal laser alone or in combination with topical estriol is a good treatment option for VVA symptoms. Sexual-related pain with vaginal laser treatment might be of concern.

The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

OBJECTIVES: To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. METHODS: A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. RESULTS: We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. CONCLUSIONS: The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Effects of ultralow topical estriol dose on vaginal health and quality of life in postmenopausal women who underwent surgical treatment for pelvic organ prolapse.

OBJECTIVE: To evaluate the efficacy of low concentrations of vaginal estriol gel in postmenopausal women with pelvic static disorders before and after vaginal surgical treatment, assessing vaginal health, sexual function, and quality of life (QoL). METHODS: Women affected by genital prolapse were enrolled. Vaginal health, QoL, and sexual function were investigated at baseline (T0), before surgery (T1), and 13 weeks after surgery (T2). At baseline, participants were randomized 1:1. Women in group A (38 women) were treated daily with vaginal gel containing 50 µg estriol for 12 weeks and women in group B (37 women) did not receive any estrogen treatment. After this period and before surgery, a first examination was carried out (T1). One week after surgical treatment, group A underwent randomization 1:1 to group A1 repeating estriol vaginal gel for 12 weeks, and group A2 discontinuing the estrogen treatment. The second follow-up examination (T2) was performed at the 13th week after surgery. RESULTS: All aspects of vaginal health improved in group A on estriol before surgery with respect to baseline (P < 0.001). After surgery, 17 participants of group A1, 16 of group A2, and 30 of group B completed the study. Group A1 (on estriol plus surgery) further improved with respect to the presurgery estriol treatment (P < 0.01). Moreover, group A2 (T2) experienced a worsening of vaginal health versus intragroup presurgery estriol treatment (P < 0.01), and versus intergroup surgical estriol treatment (P < 0.05). QoL improved in women only after surgery, with (P < 0.01) or without (P < 0.05) estriol treatment. Finally, the sexual function of participants on estriol before surgery did not change. On the contrary, it improved after surgery in both participants on estriol (P < 0.001) and without estriol (P < 0.01). Moreover, surgical estriol participants had a better score than surgical no-estriol participants (P < 0.05). CONCLUSIONS: Estriol vaginal gel (0.005%) administration significantly improved the vaginal health of natural postmenopausal women before and after vaginal surgery. Both sexual health and QoL also significantly improved after surgery.

Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule?

OBJECTIVE: The aim of this study was to evaluate the effectiveness of the application of 0.005% estriol gel to the vulvar vestibule in the management of postmenopausal dyspareunia. STUDY DESIGN: Postmenopausal women with dyspareunia were enrolled in this study. Patients were instructed to use a fingertip to apply 0.25g of vaginal gel containing 25µg of estriol to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. RESULTS: Assessment of symptoms (dyspareunia and cotton swab test) and signs of vestibular atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 63 women were included. Of the 63, 59 (93.6%) completed the 12-week treatment period, and four dropped out for vestibular burning. Dyspareunia improved or was cured (score ≤1) by week 12 in 81.4% of patients. The patients also showed a statistically significant reduction in vestibular atrophy and cotton swab test at the end of treatment. CONCLUSIONS: Application of 0.005% estriol gel to the vulvar vestibule is effective in correcting menopausal coital pain. This suggests that reduction in sensory vestibular innervation sensitivity is likely to play a pivotal role in the relief of dyspareunia. One limitation of this study is the limited follow-up, but the therapy may be continued for as long as the patients are distressed by their symptoms without estrogen intervention.

Intranasal topical estrogen in the management of epistaxis in hereditary hemorrhagic telangiectasia.

CONCLUSION: Application of topical estriol ointment is an effective treatment for hereditary hemorrhagic telangiectasia (HHT) epistaxis. OBJECTIVE: HHT is an autosomal-dominant disease characterized by epistaxis in more than 96% of patients. Management of this major symptom, epistaxis, has not been standardized. This study reports experience with topical application of estriol in patients with HHT. METHODS: Five patients with a confirmed diagnosis of HHT who first visited the hospital between 2012 and 2013 received 0.1% estriol ointment and were guided to apply the ointment twice daily to the anterior part of both nasal cavities. Severity of epistaxis was valued using epistaxis severity score (ESS) before and 3 months after initiating therapy. RESULTS: Five patients (three males, two females) received treatment. After the initiation of treatment, intensity and frequency of epistaxis became moderate in all patients. ESS decreased significantly from pre- to post-treatment (p = 0.043). No adverse events were recorded during follow-up.

Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Relapses of multiple sclerosis decrease during pregnancy, when the hormone estriol is increased. Estriol treatment is anti-inflammatory and neuroprotective in preclinical studies. In a small single-arm study of people with multiple sclerosis estriol reduced gadolinium-enhancing lesions and was favourably immunomodulatory. We assessed whether estriol treatment reduces multiple sclerosis relapses in women. METHODS: We did a randomised, double-blind, placebo-controlled phase 2 trial at 16 academic neurology centres in the USA, between June 28, 2007, and Jan 9, 2014. Women aged 18-50 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1) with a random permuted block design to either daily oral estriol (8 mg) or placebo, each in combination with injectable glatiramer acetate 20 mg daily. Patients and all study personnel, except for pharmacists and statisticians, were masked to treatment assignment. The primary endpoint was annualised relapse rate after 24 months, with a significance level of p=0.10. Relapses were confirmed by an increase in Expanded Disability Status Scale score assessed by an independent physician. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00451204. FINDINGS: We enrolled 164 patients: 83 were allocated to the estriol group and 81 were allocated to the placebo group. The annualised confirmed relapse rate was 0.25 relapses per year (95% CI 0.17-0.37) in the estriol group versus 0.37 relapses per year (0.25-0.53) in the placebo group (adjusted rate ratio 0.63, 95% CI 0.37-1.05; p=0.077). The proportion of patients with serious adverse events did not differ substantially between the estriol group and the placebo group (eight [10%] of 82 patients vs ten [13%] of 76 patients). Irregular menses were more common in the estriol group than in the placebo group (19 [23%] vs three [4%], p=0.0005), but vaginal infections were less common (one [1%] vs eight [11%], p=0.0117). There were no differences in breast fibrocystic disease, uterine fibroids, or endometrial lining thickness as assessed by clinical examination, mammogram, uterine ultrasound, or endometrial lining biopsy. INTERPRETATION: Estriol plus glatiramer acetate met our criteria for reducing relapse rates, and treatment was well tolerated over 24 months. These results warrant further investigation in a phase 3 trial. FUNDING: National Institutes of Health, National Multiple Sclerosis Society, Conrad N Hilton Foundation, Jack H Skirball Foundation, Sherak Family Foundation, and the California Community Foundation.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

OBJECTIVE: To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). STUDY DESIGN: Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. INTERVENTION(S): Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 µg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. RESULT(S): After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. CONCLUSION(S): Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.

Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor®) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors.

This study was a detailed microscopic analysis of the changes of vaginal microflora characteristics after application of 0.03 mg estriol-lactobacilli combination on the vaginal ecosystem in postmenopausal breast cancer (BC) survivors on aromatase inhibitors (AI) with severe atrophic vaginitis. A total of 16 BC women on AI applied daily one vaginal tablet of Gynoflor® for 28 days followed by a maintenance therapy of three tablets weekly for 8 weeks. During four follow up visits a smear from the upper lateral vaginal wall was analysed by phase contrast microscopy at 400 times magnification in order to classify the lactobacillary grades(LBG), bacterial vaginosis (BV), aerobic vaginitis (AV), vulvovaginal candidosis (VVC), proportional number of leukocytes and evidence of parabasal cells and epitheliolysis. LBG improved from 81% LBG-III at entry to 88% LBG-I&IIa after 2 weeks of initial therapy, which further improved upon follow up (p < 0.001). Whereas BV was a rare event, AV was frequent and substantially improved during treatment (p < 0.01). While at entry most patients had moderate or severe AV, after maintenance therapy no patient except one had AV. The number of leukocytes dropped dramatically from a score of 1.78 ± 0.70 to 1.06 ± 0.25 which was consistent till the end of the study (p < 0.01). Parabasal cells dropped from a score of 3.4 ± 0.64 at entry to 1.3 ± 0.60 at the final visit (p trend < 0.01). Starting from a low rate of Candida colonisation of 2/14 (14%), a sudden rise to 7/16 (44%) occurred after 2 weeks, to return back to base levels at subsequent visits. The vaginal use of ultra-low dose estriol and lactobacilli results in rapid and enduring improvement of all markers of the vaginal microflora and epithelial vaginal cell quality in women with breast cancer on AI with dyspareunia. Candida may develop soon after its use, but rapidly disappears again upon their prolonged use. Due to its excellent safety profiles and clinical efficacy we recommend this product as first choice in women on AI with severe dyspareunia.

Low-Dose Intravaginal Estriol and Pelvic Floor Rehabilitation in Post-Menopausal Stress Urinary Incontinence.

INTRODUCTION: Pelvic floor muscle training (PFMT) and electrical stimulation (ES) are conservative models of therapy for treating female stress urinary incontinence (SUI). The presence of estradiol receptors in the lower urinary tract advances the case for estradiol therapy in SUI. The aim of our study was to investigate the effects of the combination of pelvic floor rehabilitation and intravaginal estriol (IE) on SUI treatment in postmenopausal women. MATERIAL AND METHODS: Sixty-two women with SUI were randomized to PFMT, ES and biofeedback (Group 1) or the same treatment plus 1 mg IE (Group 2) for 6 months. Patients were evaluated with medical history, pelvic examination, urodynamics, 24-hour pad test. Urinary incontinence was evaluated using the International Consultation on Incontinence questionnaire on urinary incontinence short form and quality of life using the Incontinence Impact Questionnaire-Short Form. RESULTS: Two patients were lost at follow-up and one discontinued the study. Mean urine leakage at the 24-hour pad test dropped from 42.3 ± 20.2 g/die to 31.5 ± 14.2 g/die in Group 1 and from 48.3 ± 19.8 g/die to 22.3 ± 10.1 g/die in Group 2. Symptoms scores and incontinence status were statistically significant better in Group 2 when compared to Group 1. CONCLUSION: IE added to PFMT, ES and BF is a safe and efficacious first-line therapy in postmenopausal women with SUI.

A comparison between vaginal estrogen and vaginal hyaluronic for the treatment of dyspareunia in women using hormonal contraceptive.

OBJECTIVE: To evaluate the efficacy of topical vaginal estrogens in comparison to hyaluronic acid for the treatment of de novo dyspareunia in women using hormonal oral contraceptive (COC). STUDY DESIGN: Consecutive sexually active women using COC and complaining of de novo dyspareunia were enrolled in the study. Two attending physicians were involved in the study: the first, prescribed a 12-week vaginal estrogenic therapy with estriol 50 µg/g gel twice a week (group 1) and the second a hyaluronic acid vaginal gel therapy once a day (group 2). We evaluated dyspareunia levels using visual analogic scale (VAS) and sexual function using Female Sexual Function Index (FSFI). Vaginal atrophy was graded per the vaginal maturation index (VM). RESULTS: Overall, 31 women were enrolled. Seventeen and 14 patients were allocated in group 1 and 2, respectively. In both groups, after the topical therapy, dyspareunia, sexual function and VM were significantly improved. However, patients in group 1 experienced a significantly lower score of dyspareunia than patients in the group 2 (2 (1-7) vs. 4 (2-7); p=0.02). Additionally, women in the group 1 had higher FSFI (29.20 (24.60-34.50) vs. 28.10 (23.60-36.50); p=0.04) scores and VM (73.80 (±8.78) vs. 64.50 (±12.75); p=0.003) values in comparison to the patients in group 2. CONCLUSIONS: Our study showed that vaginal supplementation with estriol 50 µg/g gel or with hyaluronic acid could reduce the de novo dyspareunia related to COC. In this cluster of patients, both treatments improve sexuality. However, estriol 50 µg/g gel appears to be significantly more effective in comparison with hyaluronic acid.