Search

Objectives: Decreased estrogen production due to menopause is often associated with vaginal atrophy, and estrogen therapy is the most effective treatment for the management of this condition. This study investigated women's preferences relating to various aspects of local estrogen therapy (LET) for the treatment of postmenopausal vaginal atrophy., Study Design: The study involved 423 women aged >50 years who were resident in Sweden, had experienced menopausal changes in and around the vagina, and had used LET for these changes. The women completed an online questionnaire., Main Outcome Measures: The questionnaire involved a discrete choice experiment to determine women's willingness to pay for different characteristics of therapy. Time of LET appliance, use of disposable applicators with small tablets compared with both dosing syringes with vaginal cream and vagitories, and therapy that did/did not cause smudges/leakage were all considered., Results: The women had no significant preference as to the time of day LET should be used. However, quantifying other preferences suggested that respondents were willing to pay € 66.58 or € 60.32 per month extra for using disposable applicators with small tablets rather than dosing syringes with vaginal cream or vagitories, respectively, and to avoid smudges/leakage., Conclusions: This survey suggests that women may prefer using disposable applicators with small tablets to deliver LET and value therapy that does not cause smudges/leakage. It is possible that if women are able to use their preferred form of LET, improved uptake or adherence of such medication may enhance the management of postmenopausal vaginal atrophy., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate ease of insertion, acceptability and endometrial safety of a novel, miniature intrauterine, T-shaped, levonorgestrel (LNG)-releasing intrauterine system (IUS), Femilis Slim LNG-IUS (Contrel Research, Belgium), combined with parenteral estrogen substitution therapy (EST) in postmenopausal women., Design: A prospective, non-comparative, study in postmenopausal women. A 3.0 cm long and 2.0 mm wide coaxial fibrous delivery system, delivering approximately 20 microg/day of levonorgestrel (LNG) was used. The drug compartment is provided with crossarms fixed to the upper part of the drug delivery rod. The calculated duration of release of the system is at least 5 years. The majority of women received percutaneous 17beta estradiol (Oestrogel, Besins Int., Belgium), 1.5 mg daily on a continuous basis, which provides sufficient blood levels of estrogen in most women to suppress climacteric symptoms and protection against bone loss., Primary Outcome Measures: ease of insertion, retention and side effects of the T-LNG Slim IUS., Secondary Outcome Measures: endometrial safety assessed by transvaginal ultrasound examination and by endometrial biopsy in a subset of women., Results: One hundred and seventy insertions were performed in postmenopausal women with median age of age 56.6 (range 43.5-80.3). Insertion was easy in 161 (94.2%) and difficult in 9 (5.3%) women. Pain at insertion was rated as none in 57 women (33.5%), mild in 105 (61.7%), moderate in 7 (4.1%) and severe in 1 (0.5%) woman. The system was well retained in the uterus as no expulsions occurred. At the time of study analysis, the total number of women-months was 1797.5. Ninety-five women had the T-LNG-IUS in place for periods in excess of 1 year. The study was well followed-up with lost-to-follow-up rate (defined as no follow-up during 12 months) of zero at the time of study analysis. The number of women continuing the method was 160 (94.1%) including four women which were released from follow-up for various non-medical related reasons. The histological examinations conducted in 105 women showed predominantly inactive endometrium characterized by a pseudo-decidual reaction of the endometrial stroma with endometrial atrophy. The mean thickness (double-layer) of the endometrium was 3.3 mm (range 2-5 mm) which correlated well with the histology results., Conclusions: The results suggest that the small T-LNG-IUS is easy to insert in most postmenopausal women without anaesthesia and dilatation of the cervix. It is well tolerated, well accepted and effective in suppressing the endometrium during EST. The lack of expulsions of the device in this study is attributed to the optimal design characteristics of the IUS, the absence of uterine bleeding and absent or reduced contractility of the uterus. The study confirms earlier studies conducted with other LNG-releasing systems used for endometrial suppression during EST. The ease of insertion of the small LNG-IUS could be an important incentive to expand the use of the continuous combined regimen with local delivery of the progestogen. It could be a method of choice for endometrial suppression in women using EST with fundamental advantages to systemically applied progestogens which have been the subject of considerable debate as reported in the recent literature.

In the past 12 months, the FDA has approved important new pharmaceutical drugs and devices of particular interest to primary health care providers. The drugs include: Oxytrol (for urinary incontinence), Valtrex (for reducing the risk of heterosexual transmission of genital herpes), Femring (for vaginal delivery of hormone therapy), Uroxatral (for benign prostatic hypertrophy), Levitra (for erectile dysfunction), Flumist (for preventing influenza), Xolair (for asthma), Raptiva (for psoriasis), Cubicin (for skin infections), Crestor (for hypercholesterolemia), and Coreg (for severe heart failure).

The specific aim of this investigation was to utilize TCPL delivery system as a model for estrogen (E) plus progesterone (P) replacement therapy in post-ovariectomized adult rats mimicking a postmenopausal condition. A total of 20 adult female rats were used in this study. The animals were randomly divided into four different groups: groups II, III and IV were ovariectomized (OVX), OVX plus E (40 mg loaded TCPL), and OVX plus E (TCPL, 40 mg) plus P (TCPL, 80 mg) treatment. Group I animals (n = 5) served as intact control group. Blood samples were collected biweekly for 30 days. Vaginal smears were taken and screened daily during the entire investigation. The total serum levels of E, P, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by means of radioimmunoassay procedure. Data obtained from this study suggest the followings: (I) OVX resulted in an increase in total serum levels of LH and FSH within 2 days post-ovariectomy, (II) TCPL were capable of releasing sustained levels of E (10-40 pg/ml) and P (2.30-3.75 ng/ml) at the end of second day and continued until the 30th day, (III) the sustained levels of E plus P were able to suppress the post ovariectomy rise of LH and FSH to almost physiological levels, (IV) sustained delivery of E resulted in maturation of vaginal epithelium and the smears exhibited the estrus phase throughout the investigational period, and (V) sustained delivery of E + P induced no estrus and the epithelial changes resembled the OVX group.

Objective: A new matrix 17 beta-estradiol transdermal patch incorporating lauric acid to improve estradiol skin absorption has been designed for hormone replacement therapy. Estradiol pharmacokinetics obtained with the prototype, its industrial counterpart, a matrix-type, System 50, and a reservoir-type, Estraderm TTS 50, transdermal patch have been compared. Each device delivers 50 micrograms estradiol daily., Methods: Twenty postmenopausal women received each of the four formulations for 3 days in a Latin-square design and with a minimum 4-day wash-out period between treatments. Estradiol plasma concentrations were measured by radioimmunoassay at 6, 12, 24, 48 and 72 h after application., Results: The prototype patch and its industrial counterpart showed no significant difference in estradiol delivery, with 72-h systemic exposure to estradiol similar to that of the reservoir patch but greater than that of the reference matrix formulation, with average baseline-corrected concentrations (SEM) of 35 (4), 32 (3), 32 (2) and 19 (1.8) pg/ml, respectively. In addition, they ensured more stable delivery, with coefficients of variation of plasma estradiol concentrations (12-72 h) of 29, 41, 63 and 84%, respectively. All matrix patches demonstrated the same patients to be poor estradiol absorbers, different from those encountered with the reservoir patch type, despite an improved estradiol bioavailability with the lauric acid-containing matrix patch., Conclusion: Matrix patches incorporating lauric acid led to estradiol plasma levels more stable than with the reference matrix and reservoir patches, and greater than those with the reference matrix patch.

Objective: To assess the tolerance to and patient acceptability of a placebo intravaginal ring in hysterectomized, postmenopausal women over a 28-day period., Design: Open, single-center., Setting: University hospital specialist menopause clinic., Participants: A total of 24 healthy postmenopausal women attending menopause clinics at King's College Hospital and the Amarant Centre, London., Main Outcome Measures: Discomfort, ring expulsions, bowel, urinary and sexual difficulties associated with the ring and women's overall views on this method., Results: The major problems with use of the intravaginal ring were patient discomfort, involuntary ring expulsion and sexual partner discomfort. These were experienced by 13, 11 and seven women and their partners, respectively, and resulted in premature discontinuation by three women who suffered discomfort and two women who experienced recurrent involuntary ring expulsion., Conclusions: Two-thirds of the patients found the intravaginal ring acceptable, one-third did not.

Unlabelled: Estrogen replacement therapy is used in postmenopausal women with symptoms of urogenital atrophy. The aim of this study was to detect differences in efficacy of a low-dose estradiol-releasing vaginal ring and a placebo ring in the relief of symptoms of estrogen deficiency and reduction of urogenital atrophy (pH and vaginal mucosal maturation) in postmenopausal women., Design: This was a multicentre double-blind, placebo-controlled study., Patient Sample: 84 postmenopausal women, of whom 67 completed the full 24 weeks of treatment., Results: Vaginal pH decreased significantly (p = 0.0006) in the estradiol group compared with the placebo group. Similarly, in the estradiol group the mean maturation value increased significantly (p = 0.0004), while incidence of pallor and friability were significantly reduced. Patients in the estradiol group reported significantly greater relief of dyspareunia., Conclusion: The results indicate that the estradiol-releasing vaginal ring is effective and well tolerated in the treatment of local estrogen deficiency.

Objective: To compare the local tolerability and adhesion of two transdermal systems for estradiol delivery, an established membrane system (Estraderm TTS 50) and a new matrix system (Menorest)., Methods: 275 healthy female subjects participated in this two-centre, open-label, within subject comparative study. Subjects received twice-weekly application of one placebo reservoir to the right abdomen and buttock and one matrix to the left abdomen and buttock for 21 days (wearing 4 patches simultaneously). Skin irritation, pruritus (by direct questioning) and adhesion were assessed at each patch change using rating scales., Results: Overall the two systems showed comparable local tolerability and adhesion assessed by 1590 readings for each system type on buttocks and abdomen. Skin irritation occurred less frequently with Estraderm TTS than Menorest on both buttocks (11.9% vs. 15.9%) and abdomen (13.7% vs. 15.9%). The incidence of pruritus was low for both systems with over 90% of applications on buttocks and 88% on abdomen being associated with no pruritus at all. Mild pruritus was seen slightly more frequently with Estraderm TTS than Menorest on both buttock (4.8% vs. 3.3%) and abdomen (7.8% vs. 2.8%). Similar adhesion was seen for both systems on the buttocks although the incidence of patches falling off was slightly lower with Estraderm TTS compared to Menorest (8.9% vs. 13.1%). On the abdomen the pattern was reversed with slightly better adhesion for Menorest., Conclusions: The results suggest that there are no significant clinically relevant differences between the local tolerability and adhesion of an established membrane system for estradiol delivery (Estraderm TTS) and a newly introduced matrix system (Menorest).

Objective: Our purpose was to compare the effects of a new estradiol-releasing vaginal ring with progesterone given as a vaginal suppository, versus the efficacy, safety and acceptability of an intrauterine device releasing levonorgestrel combined with estradiol, delivered transdermally from a patch. Climacteric symptoms, bleeding pattern and endometrial histologic features were studied., Methods: Fifty six parous, postmenopausal women with urogenital symptoms were allocated in two groups for one year: 28 women receiving estradiol by a vaginal ring and a 100 mg vaginal progesterone suppository 7 days every month and 28 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol with a levonorgestrel-releasing intrauterine device inserted. All the patients were subjected to vaginosonographic examination followed by thorough pathological examination of the uterine curetting samples., Results: A mean endometrial thickness (double layer) of 2.9 and 3.0 mm, respectively, was found to be predictive of normal endometrium. Both treatment regiments effectively relieved climacteric symptoms. Endometrial proliferation was not observed. Spotting was more common in the intrauterine device group than in the vaginal ring group., Conclusions: Treatment of urogenital symptoms in postmenopausal women with these two forms of hormone replacement therapy is shown to be an effective and safe method, exhibiting advantages over other methods of treatment.