PubMed Health⌕ Search

Biomedical subjects

J Pryse-Davies

Publications and source records attributed to J Pryse-Davies.

At least 19 recordsLinked to original sources
PubMed1997

Randomized, double-blind, dose-ranging study of the endometrial effects of a vaginal progesterone gel in estrogen-treated postmenopausal women.

OBJECTIVE: Our purpose was to assess the endometrial effects of two doses of natural progesterone administered by a bioadhesive vaginal gel in estrogen-treated postmenopausal women. STUDY DESIGN: This was a double-blind, randomized, dose-ranging study of 31 postmenopausal women attending a specialist menopause clinic. Endometrial histologic features, sex steroid hormone concentrations, and vaginal bleeding patterns were assessed during three 28-day cycles of continuous oral conjugated estrogens (0.625 mg/day) and two doses of sequential vaginally administered natural progesterone (45 or 90 mg every 48 hours). Histologic results are presented descriptively. Between-group comparisons of other parameters were made with the use of the Mann-Whitney U and Student t tests. RESULTS: Secretory endometrium was found in 35 of 41 histologic samples that yielded adequate tissue for diagnosis. There was one case of proliferative endometrium in the 45 mg progesterone group and none in the 90 mg group and no cases of hyperplasia. Mean plasma progesterone concentrations of 4.6 ng/ml and 6.8 ng/ml were achieved in the 45 and 90 mg groups, respectively. CONCLUSIONS: Very low doses of natural progesterone, when administered vaginally in a bioadhesive gel, cause secretory endometrial transformation in estrogen-treated postmenopausal women.

Adult↗
PubMed1997

Endometrial effects of three doses of trimegestone, a new orally active progestogen, on the postmenopausal endometrium.

OBJECTIVE: To study the effects of oral trimegestone on endometrial histology and vaginal bleeding when given in combination with oral 17-beta-oestradiol. METHODS: This was a prospective, randomised, double-blind, parallel groups, pilot comparative study. Thirty-eight healthy postmenopausal women with normal endometrial histology were given oral 17-beta-oestradiol, 2 mg/day for three continuous cycles of 28 days, plus oral trimegestone, 0.10, 0.25 or 0.50 mg/day from day 15 to day 28 of each cycle. A Vabra biopsy was performed late in the oestradiol/trimegestone phase of cycle 3 and examined for histological evidence of secretory transformation of the endometrium. Characteristics of vaginal bleeding were recorded on a daily basis. RESULTS: Thirty-seven women completed the study, of whom 31 yielded adequate tissue for histological assessment. All showed secretory transformation of the endometrium. Bleeding was of earlier onset and longer duration with the lowest dose of trimegestone. CONCLUSIONS: Trimegestone is a highly effective oral progestogen for endometrial protection, all doses inducing secretory endometrial transformation. Although bleeding patterns suggest a weaker effect of the lowest dose used, the minimum effective dose for endometrial protection has still to be determined and may be lower than those used in this study.

Administration, Oral↗
PubMed1993

Does low-dose, transdermal, norethisterone acetate reliably cause endometrial transformation in postmenopausal oestrogen-users?

In a prospective study, the symptomatic, psychological and endometrial effects of a combined oestradiol/progestogen transdermal therapeutic system which delivers a low daily dose of norethisterone acetate have been investigated in 18 postmenopausal women. Treatment was given in 28 day cycles. Patients received transdermal oestradiol 50 micrograms/day continuously and transdermal norethisterone acetate, 0.1-0.15 mg/day, was added for 14 days. Treatment was given for between 5 and 7 cycles. One patient discontinued therapy because of a skin reaction. Low dose, transdermal norethisterone acetate caused few adverse symptomatic or psychological side-effects and appeared well tolerated. Fourteen endometrial samples were obtained during the combined (norethisterone acetate/oestradiol) phase of the 5th, 6th or 7th treatment cycle. None showed hyperplastic or malignant change but proliferative endometrium, indicative of an inadequate progestational stimulus, was observed in 4 biopsy samples. Three of these patients had reported breakthrough bleeding during therapy. For these reasons, we regard this dose of transdermal norethisterone acetate as inadequate in combination with transdermal oestradiol 50 micrograms/day for routine use in postmenopausal oestrogen users.

Administration, Cutaneous↗
PubMed1992

Endometrial effects of transdermal estradiol/norethisterone acetate.

The efficacy of transdermal norethisterone acetate in sequence with transdermal estradiol has been investigated in a multicenter study of 136 post-menopausal women to determine the incidence of endometrial hyperplasia, the effects on the vaginal cytology and the control of bleeding. Treatment consisted of 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day followed by 2 weeks of a new combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Endometrial histology was assessed by two pathologists. Of the 136 pre-treatment biopsies 89% provided no material, an inadequate sample or an inactive (atrophic or non-secretory) endometrium. Of the post-treatment biopsies from 110 women who completed the study: 65% showed secretory, 3% proliferative and 24% inadequate material or inactive endometrium. Hyperplasia was found in two biopsies (2%); in one of these focal atypical hyperplasia was agreed by both pathologists, in another a hyperplastic endometrial polyp was diagnosed by one pathologist. The bleeding was regular in 80% of the 1195 cycles and irregular in 11%. No bleeding occurred in 9% of the cycles. Vaginal cytology showed a significant shift towards increased maturation during treatment.

Administration, Cutaneous↗
PubMed1992

Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.

Amenorrhea↗
PubMed1991

A first study to compare two dosages of dydrogesterone in opposing the 50 mg oestradiol implant.

Thirty post-menopausal, non-hysterectomised women received a 50 mg oestradiol implant subcutaneously and either 10 mg or 20 mg dydrogesterone daily for 14 days every 28 days for 6 months. Endometrial biopsies were taken during the initial oestrogen-only phase and again during the final progestogen phase. Of the ten initial samples which were adequate for histological diagnosis, nine showed proliferative and one non-secretory endometrium. Of the 28 samples obtained at the end of the study during the progestogen phase, all except one showed satisfactory conversion, irrespective of dose. Acceptable bleeding patterns were seen in both dosage groups. Tolerance was good and no patient discontinued treatment. This study has shown that both 10 mg and 20 mg dydrogesterone for 14 days are potent enough to oppose the proliferative effects of the 50 mg oestradiol implant. In view of the wide inter-patient variation in endometrial response to progestogens, it appears appropriate to choose the dosage of dydrogesterone on the basis of cycle control and tolerability, whilst being able to maintain confidence in endometrial protection.

Biopsy↗
PubMed1991

Extramammary Paget's disease of the vulva with dermal invasion and vulval intra-epithelial neoplasia.

Vulval biopsies from a 66-year-old lady complaining of pruritus showed intraepithelial Paget's disease. On simple vulvectomy, extramammary Paget's disease was found to be associated with vulval intra-epithelial neoplasia (VIN III) and superficial dermal invasive adenocarcinoma. Bilateral inguinal lymphadenectomy later revealed metastatic spread of the tumour. We believe this is a unique combination and discuss the possible origins in relation to this lady's past medical history of breast carcinoma 20 years and spinal metastases 17 years before.

Adenocarcinoma↗
PubMed1991

The histologic reliability of laser cone biopsy of the cervix.

Laser conization of the cervix has been advocated as the technique of choice for the treatment of cervical intraepithelial neoplasia (CIN) in preference to ablative techniques, because it provides a specimen for histologic diagnosis while retaining the advantages of an outpatient procedure with minimal short- and long-term morbidity. To determine whether specimens so obtained are adequate for reliable histologic diagnosis, we reviewed 77 laser conizations performed for lesions confirmed to contain CIN in a colposcopically directed biopsy and satisfying the criteria for local ablation and scored the cones for the presence of epithelial denudation and laser coagulation artifact that interfered with the diagnosis of CIN or the assessment of the margins of excision. Thirty specimens (39%) were negative for CIN. Twenty-eight (36%) showed extensive epithelial denudation, ten (13%) contained coagulation artifact that made recognition of CIN extremely difficult or impossible, and in 11 (14%), assessment of margins was extremely difficult or impossible because of laser coagulation artifact. We conclude that these difficulties with the histologic interpretation of laser cone specimens make it an unsuitable excisional technique when reliable histologic diagnosis of cervical lesions is required.

Adult↗
PubMed1990

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study.

The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

Administration, Cutaneous↗
PubMed1990

Influence of superovulation on endometrial and embryonic development.

The authors have studied the temporal relationship between follicular rupture and endometrial development in 13 women during a natural ovarian cycle (length 25 to 35 days), and subsequently after standard treatment with clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin (hCG) to induce multiple folliculogenesis for oocyte recovery, in vitro fertilization, and embryo freezing (cycle length 23 to 27 days). An endometrial biopsy was taken during both cycles 1.5 to 2.0 days after the oocytes had been released or removed. The samples were examined by light and transmission electron microscopy. Samples of peripheral blood were taken at defined times for hormone analysis. After treatment 11 subjects (85%) had advanced morphological development of the endometrium (8 women by 3 to 4 days, 3 women by 1 to 2 days). The concentrations of plasma estradiol (E2) and progesterone (P) on the days of follicular rupture and endometrial biopsy were significantly raised in the treatment cycles. The concentration of total urinary estrogens on the day of hCG administration and the mean change in the concentration of plasma E2 (treatment/control) on the days of endometrial biopsy were positively correlated with the extent of endometrial advancement. In addition, the mean change in the concentration of plasma P (treatment/control) was markedly increased on the days of follicular rupture and endometrial biopsy in those subjects with an advanced endometrium. Embryonic development was not so obviously related to the extent of superovulation. Asynchronous endometrial and embryonic development may therefore contribute to the low pregnancy rate in these patients.

Adult↗
PubMed1990

Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone.

Sixteen postmenopausal women receiving conjugated equine oestrogens 1.25 mg/day, continuously, were randomly allocated to add dydrogesterone 20 mg/day for 12 days each calendar month for 3 months and then 10 mg/day in an identical fashion for a further 3 months, or to receive the dydrogesterone doses in reverse sequence. The effects of the two dydrogesterone doses on endometrial histology, vaginal bleeding, and the symptomatic and psychological status were compared. Endometrial samples were obtained around day 10 of progestogen addition. Dydrogesterone, 20 mg, induced uniform, late secretory transformation in all samples; with 10 mg one sample showed mixed early and late secretory features and another demonstrated late secretory changes associated with atypical hyperplasia. Both dydrogesterone doses induced an acceptable withdrawal bleed; most bleeding episodes were 'spotting' or normal in amount, and heavy bleeding was reported infrequently. There was one episode of breakthrough bleeding. There were no differences in bleeding patterns between the two dose regimens. Anxiety, and the physical and psychological status were significantly improved after 3 months of therapy. Significant benefits on depression were observed less clearly. There were no differences between the two dydrogesterone doses on anxiety, depression and the physical and psychological status, and, overall, the addition of the progestogen did not antagonize oestrogen benefits.

Affective Symptoms↗
PubMed1990

Reliability of colposcopy and directed punch biopsy.

A group of 118 women underwent laser cone biopsy. Data were collected routinely on proforma case notes and entered into a computerized database. The histology of the cone biopsies was compared with that of previous, colposcopically directed punch biopsies, with the cytology of smears taken in the clinic and with the colposcopic diagnosis. The punch biopsy had a 54% false negative rate and neither of the two microinvasive carcinomas biopsied in this way were detected by the biopsy. Ten of 24 women with negative punch biopsies had CIN III in the cone. When the punch biopsy showed CIN II or worse, the cone biopsy confirmed the presence of CIN in 86%. There was some evidence of false negative cone biopsies. The data suggest that management should not be based solely upon the punch biopsy result but should include consideration of the cytology and colposcopy findings. Excisional methods of treatment are more likely to reveal early invasion and adenocarcinoma-in-situ.

Biopsy↗
PubMed1989

The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy.

Progestogens are added to the oestrogen treatment for 10-12 days each cycle in order to prevent endometrial abnormalities. However, concern has been expressed about the safety of certain of the currently available progestogens because of the potential adverse metabolic effects. We have evaluated the effects of nomegestrol acetate - non-androgenic progestogen - for administration to post-menopausal oestrogen users. Thirty-six (36) women receiving 50 mg oestradiol implants at regular intervals also took nomegestrol acetate for 12 days each calendar month at doses of 0.5 mg, 1.0 mg and 2.5 mg daily. Allocation to one of the dose regimens was random. Physical and psychological side-effects were recorded and all vaginal bleeding was noted: an endometrial biopsy was performed on the sixth day of progestogen addition for histological, ultrastructural and biochemical evaluation. Adverse side-effects were responsible for a dose-dependent drop out rates of 17%. All patients experienced a regular, progestogen-induced withdrawal bleed each month; and histological, ultrastructural and biochemical changes were induced within the endometrium by all 3 doses. Nomegestrol acetate is a potent progestogen and further studies are required to determine its lowest effective dose.

Adult↗
PubMed1989

Are fixed-dose oestrogen/progestogen combinations ideal for all HRT users?

Although progestogens protect the endometrium against excessive oestrogen-induced stimulation, they can cause adverse symptomatic and psychological effects and may have undesirable metabolic consequences. Thus, the minimum progestogen dose which results in consistent endometrial transformation should be prescribed. To define this dose for norethisterone and dl-norgestrel, 197 endometrial samples obtained from postmenopausal women receiving conjugated equine oestrogens (0.625 mg or 1.25 mg daily) with one of six doses of norethisterone (or the acetate), or one of three doses of dl-norgestrel added for the first 12 days of each calendar month were examined with the light microscope; 109 samples were also assessed by transmission electron microscopy. There was an inverse relation between the percentage of samples showing proliferative features and the progestogen dose. However, proliferative endometrium was observed in 6% of samples with the highest dose of dl-norgestrel (500 micrograms) and in 3% of samples with 2.5 mg norethisterone. Conversely, complete secretory transformation was observed in 25% of samples with the lowest dose of norethisterone (0.1 mg) and in 40% of samples with 75 micrograms dl-norgestrel. Mild atypical hyperplasia was diagnosed in four samples. There was a wide inter-patient variation in response and none of the nine progestogen dose regimens induced secretory change in every patient.

Cell Division↗
PubMed1986

A simple method for determining the optimal dosage of progestin in postmenopausal women receiving estrogens.

Progestin is often added to regimens of estrogen therapy in postmenopausal women to reduce the risk of endometrial hyperstimulation, but it may cause undesirable metabolic effects. Therefore, a low dosage is recommended. At present, the only way to determine whether the dosage of progestin is causing the desired secretory transformation of the endometrium is by endometrial sampling, which is invasive. We studied 102 postmenopausal women undergoing estrogen therapy who also took a progestin for 12 days each month, and we correlated the day of onset of bleeding with the endometrial histology over a three-month period. A bleeding pattern suitable for interpretation was observed in 96 women. Regardless of the preparation and dosage of the estrogen and progestin used, wholly or predominantly proliferative endometrium was always associated with bleeding on or before day 10 after the addition of progestin; wholly or predominantly secretory endometrium, or a lack of endometrial tissue, was associated with bleeding on day 11 or later. We conclude that the bleeding pattern reflected the histologic condition of the endometrium and that adjustment of the dosage of progestin so that regular bleeding is induced on or after day 11 may obviate the need for endometrial biopsy.

Adult↗
PubMed1986

Effects of dydrogesterone on the oestrogenized postmenopausal endometrium.

Postmenopausal women receiving conjugated oestrogens 1.25 mg daily continuously were also given dydrogesterone either 5, 10 or 20 mg daily for the first 12 days of each calendar month. Endometrial tissue obtained on the sixth day of combined therapy in the third or subsequent treatment cycle was subjected to histological, ultrastructural and biochemical assessments. Dydrogesterone provoked secretory histological and ultrastructural changes within the endometrium in a dose-dependent manner. A daily dose of 5 mg produced sub-optimal responses but 10 and 20 mg daily produced effects similar to those observed in the secretory phase of the ovulatory cycle. Dydrogesterone 10 mg and 20 mg daily reduced epithelial DNA synthesis and nuclear oestradiol receptor levels to values within the secretory phase range. A dose-response relation was seen in the induction of oestradiol-17 beta and isocitrate dehydrogenase activities; hyperphysiological values were observed with 20 mg of dydrogesterone daily. This study has demonstrated that dydrogesterone exerts potent anti-oestrogenic and progestational effects on the human endometrium which are dose-related. The 10 and 20 mg doses induced responses equal to or greater than those observed in the secretory phase of the ovulatory cycle and both dosages can be recommended for use in combination with exogenous oestrogens in postmenopausal women: and they may also have a role in the management of anovulatory dysfunctional uterine bleeding.

Cell Nucleus↗
PubMed1986

Oestriol with oestradiol verses oestradiol alone: a comparison of endometrial, symptomatic and psychological effects.

In a prospective, double-blind, randomized, cross-over trial, the effects of oral oestradiol, 2 mg daily, on the endometrial histology, frequency and severity of vaginal bleeding, and the symptomatic and psychological status of postmenopausal women were compared with those of oral oestradiol, 2 mg daily, plus oestriol, 1 mg daily. Both therapies were prescribed for 3 months on a cyclical basis. The addition of oestriol to oestradiol did not modify the endometrial response. The prevalence of proliferative/hyperplastic endometrium (64%: 9 of 14 biopsies) was similar after both treatments and there were no significant differences in either the frequency or heaviness of vaginal bleeding. Both therapies significantly reduced hot flushes, night sweats and vaginal dryness: no significant differences in effect on the symptomatic and psychological status were recorded. The addition of 1 mg of oestriol to 2 mg of oestradiol did not confer any benefit and the value of such an addition is challenged.

Adult↗