THE MECHANISM IN INHIBITION OF OVULATION IN ORAL CONTRACEPTION. I.

1966 ◽  
Vol 51 (3) ◽  
pp. 469-480 ◽  
Author(s):  
J. Stamp
Keyword(s):  
Methyl Ether ◽  
Oral Contraception ◽  
Megestrol Acetate ◽  
Significant Suppression ◽  
Short Intervals ◽  
Pre Treatment ◽  
Cessation Of Treatment ◽  
Marked Suppression ◽  
Fertile Women

ABSTRACT A review is given of previous investigations on the excretion of pituitary gonadotrophins during treatment with gestagens, oestrogens or the combination of both. In the present study 14 fertile, 7 menopausal, and 9 oophorectomized women were treated with 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 17α-ethynyl-oestradiol-3-methyl-ether (mestranol) for a period of 3 to 61 weeks. The fertile women were given 5 mg of megestrol acetate + 0.1 mg of mestranol cyclically, and the menopausal and oophorectomized women were given the same dose of megestrol acetate + mestranol continuously. The excretion of total pituitary gonadotrophins was determined at short intervals during treatment and during the period following cessation of treatment. There was a significant suppression of the total pituitary gonadotrophins in 22 out of the 30 patients, and in 19 patients the excretion became undetectable. This marked suppression of total gonadotrophins occurred after 2 to 60 weeks of treatment (an average of 15 weeks). The gonadotrophin output reached pre-treatment levels 2 to 7 weeks (an average of 4 weeks) after the treatment was discontinued.

EXCRETION OF GONADOTROPHINS DURING GESTAGEN- AND OESTROGEN-TREATMENT

1967 ◽  
Vol 54 (4) ◽  
pp. 637-644 ◽  
Author(s):  
J. Starup
Keyword(s):  
Synergistic Effect ◽  
Megestrol Acetate ◽  
Significant Suppression ◽  
Oestrogen Treatment ◽  
End Of Treatment ◽  
Daily Dose ◽  
Pre Treatment

ABSTRACT 5 menopausal and 12 oophorectomized women aged 31 to 56 were divided in two comparable groups. The first group was treated with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) continuously, and the second group received a daily dose of 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) also continuously. The patients were observed for 12 to 63 weeks. The excretion of total pituitary gonadotrophins was determined every 2 to 4 weeks during treatment and every week during the period after the end of treatment. During treatment with megestrol acetate it was characteristic of all 9 patients in this group that the excretion of gonadotrophins showed very marked variations from time to time, but in none of the 9 patients was there any significant suppression of the gonadotrophins. During treatment with mestranol there was a significant suppression of the gonadotrophins in 7 out of the 8 patients in this group, and in 3 patients the excretion became undetectable. The suppression of gonadotrophins occurred gradually over a period of about 4 months. The gonadotrophin output reached pre-treatment levels 2 to 9 weeks (an average of 5 weeks) after treatment was discontinued. This effect of megestrol acetate and mestranol respectively on the excretion of total pituitary gonadotrophins was compared with the effect of a combination of both substance reported in a previous paper. With this combination it seems to be the oestrogen exclusively which causes the suppression of total gonadotrophins. No synergistic effect of the oestrogen and the gestagen was found.

CONTRACEPTION BY AN INJECTABLE LONG-ACTING OESTROGEN-PROGESTOGEN AGENT. II.

1970 ◽  
Vol 65 (4) ◽  
pp. 683-697 ◽  
Author(s):  
Rolf Plesner
Keyword(s):  
Side Effects ◽  
Cycle Length ◽  
Clinical Investigation ◽  
Oral Contraception ◽  
The Mean ◽  
Pre Treatment ◽  
Long Acting ◽  
Mean Cycle ◽  
Fertile Women

ABSTRACT The results of a clinical investigation on 22 fertile women treated cyclically with a total of 341 injections of Deladroxate, an injectable, long-acting oestrogen-progestogen are presented. The injections were administered on the 8th (7th–9th) day of each cycle. Before treatment, the patients were observed through 2 cycles for cycle length as well as duration and amount of flow. In some cases the dose was increased because of a shortening of the cycle. The over all mean cycle length during the treatment was 25.3 days, though with fairly marked variations. The mean cycle length before treatment was 28.4 days. The duration of flow ranged from 1–30 days. About 72% of 320 withdrawal bleedings lasted for 4–8 days. Of the flows 60% were of normal amounts, while the majority of the remaining flows were scantier than the normal pre-treatment flows of the subjects. Side effects during treatment were recorded in one or more cycles in 17 of the 22 subjects and were in most cases slight and transient. The most common complaints were breast tenderness, oedema, and irregularities of bleeding. No pregnancy occurred during treatment. After discontinuation of the injections, bleedings and cycles normalized spontaneously in 11 women. In 1 woman curettage was performed because of profuse flow, and 2 women were treated with oral oestrogen-progestogens because of persistent bleeding. Eight women started oral contraception before the cycles became regular.

CONTRACEPTION BY AN INJECTABLE LONG-ACTING OESTROGEN-PROGESTOGEN AGENT. III

1972 ◽  
Vol 69 (1) ◽  
pp. 67-76
Author(s):  
Rolf Plesner
Keyword(s):  
Treatment Period ◽  
Treatment Cycle ◽  
Post Treatment ◽  
Mixed Phase ◽  
Discontinuation Of Treatment ◽  
Phase Type ◽  
Secretory Type ◽  
Pre Treatment ◽  
Long Acting ◽  
Fertile Women

ABSTRACT Twenty-two fertile women were treated cyclically in from 4–30 cycles (mean 15.5) with a total of 341 injections of Deladroxate®, an injectable, long-acting oestrogen-progestogen. The injections were administered on the 8th (7th–9th) day of each cycle. Before treatment, the last pre-treatment cycle was controlled by means of daily recordings of the basal body temperature (BBT), urinary excretion of pregnanediol and total pituitary gonadotrophins at certain intervals, and by endometrial biopsies obtained late in the cycle. The effects of Deladroxate® on ovulation, on pituitary gonadotrophic function, and on the endometrium were controlled by the above mentioned parameters during cycles 1, 3, and 6, and all assessments were repeated after discontinuation of treatment. During treatment, there was a statistically significant fall in gonadotrophin excretion values (as compared with the pre-treatment values), and the fall was found to be gradually progressive during treatment. After discontinuation of treatment, there seemed to be a tendency towards an increase in the excretion values. Suppression of ovulation as determined by means of the pregnanediol excretion during treatment, was effective in nearly all of the treatment cycles checked. The fall in pregnanediol excretion was also gradually progressive during treatment, while there was a slight increase in excretion values in the post-treatment period. During treatment, 79 BBT curves were recorded. Nearly 50 % were monophasic, indicating anovulatory cycles, 17 curves were biphasic, but with the rise in temperature occurring at non-characteristic times in the cycles, 18 curves were classified as thermogenic because of a rise in temperature occurring within 24 hours after the injection, and 5 curves were not assessable. During the first month after discontinuation of treatment, 8 out of 10 recorded curves were monophasic. Out of 53 endometrial biopsies obtained around the 23rd day of the cycle, 31 were of the mixed phase type, but showing a predominance of proliferative patterns, 15 were of the secretory type, and 7 were purely proliferative. Out of 15 biopsies obtained in the post-treatment period, only two were of the mixed phase type, 12 were proliferative and one was purely secretory.

OCCURRENCE AND FUNCTION OF CORPORA LUTEA DURING DIFFERENT FORMS OF ORAL CONTRACEPTION

1968 ◽  
Vol 57 (3) ◽  
pp. 386-394 ◽  
Author(s):  
E. Østergaard ◽  
J. Starup
Keyword(s):  
Corpus Luteum ◽  
Megestrol Acetate ◽  
Corpora Lutea ◽  
Impaired Function ◽  
Daily Dose ◽  
The Subject ◽  
And Function ◽  
Late Part ◽  
Fertile Women

ABSTRACT 144 fertile women were treated cyclically with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) for a period of 1 to 24 months. The excretion of pregnanediol on days 21 to 23 never exceeded 0.9 mg/day, and there was no correlation between the excretion of pregnanediol and the length of the treatment period. In 62 fertile women it was shown by laparotomy, that inhibition of ovulation was extremely reliable when treatment with megestrol acetate + mestranol was initiated at the latest on day 7. If the treatment was started later than day 7 then the inhibition of ovulation was increasingly unreliable, and from day 10 there was no inhibition of ovulation. As could be expected the excretion of pregnanediol on day 23 was invariably low in all patients who did not show any sign of recent ovulation. More surprising was the finding of a low excretion of pregnanediol in 6 patients in whom fresh corpora lutea were found at laparotomy on day 24. This finding might be due either to an impaired function of the corpus luteum or to an influence of the steroids on the metabolism of progesterone or on the analysis used for the determination of pregnanediol. This problem has been the subject of more detailed studies. 16 fertile women underwent laparotomy on days 24 to 26, and in the cycle in which the laparotomy was performed, treatment was initiated on day 10 or later with megestrol acetate only, mestranol only, or the combination of both substances. All patients showed fresh corpora lutea. It was observed that not only megestrol acetate + mestranol, but also megestrol acetate only suppressed the excretion of pregnanediol in the late part of the cycle when treatment was initiated before ovulation, whereas mestranol only caused no decrease in the pregnanediol excretion. If treatment with megestrol acetate + mestranol was started after ovulation then the excretion of pregnanediol was not suppressed, but the luteal phase was shorter than usual. In addition, it was observed in 3 postmenopausal women, that megestrol acetate caused no significant changes in the excretion of pregnanediol following intramuscular administration of progesterone. It is therefore concluded that the low excretion of pregnanediol observed during treatment with megestrol acetate + mestranol in patients showing fresh corpora lutea, is due to an impaired function of the corpus luteum and not to a change in the metabolism of progesterone. Furthermore, it appears that megestrol acetate is responsible for this effect.

THE MECHANISM IN INHIBITION OF OVULATION IN ORAL CONTRACEPTION. III.

1967 ◽  
Vol 56 (2) ◽  
pp. 188-196 ◽  
Author(s):  
J. Starup ◽  
P. E. Lebech
Keyword(s):  
Body Temperature ◽  
Treatment Cycle ◽  
Oral Contraception ◽  
Megestrol Acetate ◽  
Complete Disappearance ◽  
Basal Body Temperature ◽  
Daily Dose ◽  
Daily Excretion ◽  
Menstruating Women ◽  
All Treatment

ABSTRACT Six normally menstruating women aged 21 to 28 were studied for 3 cycles, viz. one control cycle followed by two cycles in which they were treated from day 5 to day 24 with daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol). In all 3 cycles the daily excretion of total pituitary gonadotrophins and luteinizing hormone (LH) was determined from day 8 to day 21. In addition, the excretion of pregnanediol was determined on days 7 and 22 in every cycle, and the basal body temperature was recorded daily for the entire period. In the control cycle 4 out of the 6 patients showed a definite mid-cycle peak in the excretion of total gonadotrophins, whilst a definite mid-cycle peak in the excretion of LH was found in 4 patients and a more questionable peak of LH in the remaining 2 patients. All 6 patients showed typical biphasic temperature curves and the excretion of pregnanediol on day 22 indicated normal ovulatory cycles. In the first treatment-cycle, 5 out of the 6 patients already showed no mid-cycle peak in the excretion of total gonadotrophins. The last patient had only a small questionable peak. A similar pattern was seen in the excretion of LH. All the 4 patients who had a definite mid-cycle peak of LH in the control cycle now showed a complete disappearance of this peak, while the remaining 2 patients showed only a questionable peak. In the second treatment-cycle none of the 6 patients showed a mid-cycle peak in the excretion of total gonadotrophins, and only 2 out of the 6 patients had a questionable peak in the excretion of LH. Furthermore, in all treatment-cycles the excretion of pregnanediol was less than 0.8 mg/day on day 22. Thus the present investigation indicates that the combination of megestrol acetate and mestranol inhibits ovulation and suppresses the synthesis and/or the release of LH.

THYROID FUNCTION IN ORAL CONTRACEPTION

1967 ◽  
Vol 56 (3) ◽  
pp. 525-532 ◽  
Author(s):  
J. Starup ◽  
T. Friis
Keyword(s):  
Treatment Period ◽  
Thyroid Function ◽  
Megestrol Acetate ◽  
Cell Uptake ◽  
Continuous Treatment ◽  
Red Cell ◽  
Normal Limits ◽  
Menopausal Women ◽  
Observation Period ◽  
Fertile Women

ABSTRACT Eighty one euthyroid, fertile women were treated cyclically with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) for an average of 16 months. During treatment a definite, but not significant, increase in protein-bound iodine (PBI) was found. In 11 normal fertile women, the thyroid function was evaluated before, during, and after cyclical treatment with megestrol acetate + mestranol. The observation period was 4 to 19 months. The thyroidal 4-hour uptake and 24-hour uptake of 131I and the uptake of 131I-triiodothyronine (T3) by erythrocytes and resin (Triosorb*) were determined at short intervals. No significant changes were observed in the two first mentioned tests, but it was characteristic of all patients except one, that the red-cell uptake of T3 was significantly decreased to values below the lower limit of normal, within 1 to 2 months of the commencement of treatment, and that it then remained unchanged during the remainder of the treatment period. One month after treatment was discontinued, all patients except two showed values within normal limits. The uptake of T3 by resin showed similar patterns during the treatment period, but one month after the medication was withdrawn, only 2 out of the 9 patients had values within the normal range. In 5 menopausal women, the thyroid function was evaluated before, during, and after continuous treatment with megestrol acetate by means of the same parameters as in the former group of patients. The observation period was 4 to 6 months. No significant changes were observed in the 4 indices of the thyroid function during and following treatment with megestrol acetate alone. It is therefore concluded that the significant decrease in the red-cell uptake and resin uptake of T3 observed during treatment will megestrol acetate + mestranol is caused exclusively by the oestrogen in this combination.

PITUITARY-ADRENAL FUNCTION IN ORAL CONTRACEPTION

1966 ◽  
Vol 53 (1) ◽  
pp. 1-12 ◽  
Author(s):  
J. Starup ◽  
V. Sele ◽  
O. Buus
Keyword(s):  
Plasma Cortisol ◽  
High Plasma ◽  
Plasma Cortisol Level ◽  
Megestrol Acetate ◽  
List Type ◽  
Cortical Function ◽  
Acth Stimulation ◽  
Menstruating Women ◽  
Pre Treatment ◽  
Short Time

ABSTRACT 14 normally menstruating women aged 17 to 29 were treated cyclically with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) for a period of 3 to 74 weeks. During treatment we found a gradual decrease in the excretion of both 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS). After cessation of treatment, we found a rapid increase to pre-treatment levels in the excretion of both 17-KGS and 17-KS. The decrease in the output of 17-KGS and 17-KS observed during treatment with megestrol acetate + mestranol might be explained by: a suppression of the pituitary function a suppression of the adrenal cortical function a change in the metabolism of the corticosteroids. The purpose of the present investigation was to explore these hypotheses. 8 patients were treated with the above mentioned dose of megestrol acetate + mestranol until the excretion of pituitary gonadotrophins was significantly suppressed. This occurred after a treatment-period of 3 to 10 months. In all 8 patients we determined the responsive to metyrapone before the treatment started and a short time before the treatment was discontinued. During treatment all 8 patients showed a normal response to oral administration of metyrapone. Furthermore, in 6 out of the 8 patients we tested the response of the adrenal cortex to intravenous and intramuscular administration of corticotrophin (ACTH) just before the treatment was discontinued. In all patients a normal ACTH-stimulation test was found. During treatment, the concentration of plasma cortisol was significantly increased to values about 3 times the control values, whereas the concentration of plasma 11-deoxycortisol (compound S) remained unchanged. This high plasma cortisol level during treatment is probably caused by an increased protein-binding of cortisol. As both the responsive to metyrapone and to ACTH is normal during treatment with megestrol acetate + mestranol, we are of the opinion that the decrease observed in the excretion of 17-KGS and 17-KS is due to a change in the metabolism of the corticosteroids.

THE EFFECT OF ADRENOCORTICOTROPHIC HORMONE ON THE YIELD AND COMPOSITION OF THE MILK OF THE COW

1954 ◽  
Vol 10 (4) ◽  
pp. 333-339 ◽  
Author(s):  
D. S. FLUX ◽  
S. J. FOLLEY ◽  
S. J. ROWLAND
Keyword(s):  
Protein Content ◽  
Milk Yield ◽  
Percentage Reduction ◽  
Adrenocorticotrophic Hormone ◽  
Significant Fall ◽  
Pre Treatment ◽  
Long Acting ◽  
Sodium And Potassium ◽  
Cessation Of Treatment

SUMMARY A long-acting preparation of ACTH depressed the milk yields of cows when given in single doses of 100 or 200 i.u., or when a 100 i.u. dose was given every second day, and the extent of the decline in milk yield was correlated with the percentage reduction in the number of circulating eosinophils. Milk yields returned to or almost to pre-treatment levels soon after the cessation of treatment. The composition of the milk was changed only slightly as a result of ACTH administration, the butterfat and protein content being increased, while the lactose content showed a small, but not statistically significant, fall. The quantities of sodium and potassium showed no change which could be attributed to the treatment.

KLINISCH-EXPERIMENTELLE STUDIEN MIT MENSCHLICHEM HYPOPHYSÄREM GONADOTROPIN

1962 ◽  
Vol 41 (1) ◽  
pp. 14-30 ◽  
Author(s):  
Michael Apostolakis ◽  
Gerhard Bettendorf ◽  
Klaus D. Voigt
Keyword(s):  
Single Case ◽  
Endometrial Biopsy ◽  
Vaginal Smear ◽  
List Type ◽  
Clinical Effects ◽  
Pituitary Insufficiency ◽  
Clinical Control ◽  
Treatment Changes ◽  
Pre Treatment ◽  
Cessation Of Treatment

ABSTRACT Gonadotrophin extracted from human hypophyses (HHG) was administered in clinical trials to 5 amenorrhoic women. Gonadotrophin levels in the blood and urine and the urinary excretion of oestrogen, pregnanediol, 17-hydroxycorticosteroids, 17-ketosteroids and pregnanetriol were determined before, during and after treatment. Clinical control methods included endometrial biopsy and vaginal smear examination. Following the i. m. administration of HHG the gonadotrophin excretion increased markedly within the first 24 hours. Plasma gonadotrophin increased to substantially higher levels within 4–6 hours after the first injection. After cessation of treatment both plasma and urine gonadotrophin concentration returned slowly within 2–4 days to the pre-treatment levels. Following treatment, all 4 patients with hypogonadotrophic amenorrhoea (primary pituitary insufficiency) responded by an increased oestrogen and pregnanediol production. It would seem therefore that HHG-treatment had succeeded in producing ovulation. The single case of hypergonadotrophic amenorrhoea (primary ovarian insufficiency) showed no response in this respect. No change in 17-OHCS excretion was effected by the HHG-treatment. Changes in 17-ketosteroids and pregnanetriol excretion did not show a constant pattern. The clinical effects obtained in the 4 hypogonadotrophic amenorrhoea cases are confirmed in that ovulation was induced by means of the treatment.

scholarly journals Menstrual Headache in Women with Chronic Migraine Treated with Erenumab: An Observational Case Series

2021 ◽  
Vol 11 (3) ◽  
pp. 370
Author(s):  
Raffaele Ornello ◽  
Ilaria Frattale ◽  
Valeria Caponnetto ◽  
Eleonora De Matteis ◽  
Francesca Pistoia ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Treatment Period ◽  
Case Series ◽  
Single Center ◽  
Menstrual Cycles ◽  
Pre Treatment ◽  
Fertile Women

Background: We aimed to assess the differences between menstrual and non-menstrual headache in women with chronic migraine treated with erenumab. Methods: We included fertile women from a single center. Patients were defined as responders to erenumab if reporting a ≥50% decrease in monthly headache days, as compared to pre-treatment for more than half of the treatment period. Premenstrual days were defined as the two days preceding menstruation, while menstrual days were defined as the first three days of menstruation. Results: We included 18 women (11 erenumab responders and 7 erenumab non-responders) contributing to a total of 103 menstrual cycles and 2926 days. The proportion of headache days was higher in menstrual than in premenstrual and non-menstrual days in erenumab responders (34.4% vs. 14.8% vs. 16.3%, respectively; p < 0.001) and in erenumab non-responders (71.4% vs. 53.6% vs. 48.3%, respectively; p < 0.001). Headache days with ≥2 acute medications were higher in menstrual than in premenstrual or non-menstrual headache days in erenumab non-responders (p = 0.002) but not in erenumab responders (p = 0.620). Conclusions: Our data suggest that migraine is more frequent during than outside menstrual days even in women treated with erenumab.

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