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Biomedical subjects

J Endacott

Publications and source records attributed to J Endacott.

6 recordsLinked to original sources
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↗
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

Absorption and metabolism of oral progesterone when administered twice daily.

The absorption, metabolism, and clearance of progesterone (P) from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg at 9:00 A.M. and 200 mg at 9:00 P.M. for 5 consecutive days. Mean peak plasma concentrations of P were observed 2 hours after ingestion of both the 100 and 200 mg doses and were 22.7 and 47.7 nmol/l, respectively. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment; those of 17-hydroxyprogesterone were least raised. Increases in the plasma levels of 20 alpha-dihydroprogesterone were more sustained than those of P, and the plasma concentrations remained elevated at approximately 20 nmol/l for at least 12 hours after P administration. We conclude that administration of oral P 100 mg in the morning and 200 mg at night increases the circulating concentrations of P and the biologically active metabolite 20 alpha-dihydroprogesterone, and that the duration of these increases is sufficient to evoke progestational responses in responsive end-organs.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Endometrial responses to transdermal estradiol in postmenopausal women.

In prospective studies, we have determined the endometrial histologic characteristics and patterns of vaginal bleeding in 12 perimenopausal or postmenopausal women during administration of transdermal estradiol, 0.05 mg daily, given either alone or in combination with a progestogen. In the first study, we administered transdermal estradiol in cyclical fashion for 3 months. Outpatient curettage at pretreatment produced no endometrial sample or tissue too scant for assessment from 10 of the 12 patients (83%). At the end of therapy, proliferative or nonsecretory endometrium was diagnosed in nine patients (75%). Eight patients experienced treatment-related vaginal bleeding but no regular pattern, and seven patients reported breakthrough bleeding. Eight patients participated in the second study in which transdermal estradiol was administered continuously and norethindrone, 0.35 mg, was added for 12 days of each calendar month. A further curettage was performed at the end of treatment, and proliferative endometrium was the most common finding. No endometrial hyperplasia was observed. Only one patient experienced breakthrough bleeding. There were no consistent changes with time in the number of patients bleeding each month or in the duration or heaviness of the bleeding.

Administration, Topical↗
PubMed1985

Efficacy, acceptability, and metabolic effects of transdermal estradiol in the management of postmenopausal women.

Systemic side effects that result from oral administration of estrogens to postmenopausal women may be minimized by use of the transdermal route. We administered transdermal estradiol, 0.05 mg/day, cyclically for 3 months to 12 postmenopausal and perimenopausal women to study the efficacy, acceptability, and metabolic effects of this dosage form. The results showed that transdermal estradiol significantly increased plasma levels of estradiol and estrone and urinary concentrations of estradiol conjugates, and produced significant improvement in menopausal symptoms and vaginal cytologic findings. The patches were well tolerated and no systemic side effects were reported. No clinically significant adverse biochemical changes were observed. Plasma renin substrate and renin activity were unchanged during therapy.

Administration, Topical↗