The Role of Progestogens in the Hormonal Control of Fertility

Rudel, Harry W.; Martínez-Manautou, J; Maqueotopete, M

doi:10.1016/s0015-0282(16)35522-4

Cited by 92 publications

(13 citation statements)

References 8 publications

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“…However, in a subsequent experiment (Tables 2 and 3), a 'break¬ through' in ovulation was observed in some rats when 10 µg of ethynyloestradiol or AY-11483 was given daily during the pre-ovulatory period in combination with 100 µg of chlormadinone acetate or AY-11440. Similar effects with oral contraceptives were suggested in human trials (Rudel, Martinez-Manautou & Maquco-Topete, 1965). Since a single administration of 100 µg of either ethynyloestradiol or AY-11483 did not prevent ovulation (Table 2), but pre¬ cluded implantation (Table 4), it is believed that the process of implantation in rats is more vulnerable to these oestrogens than is ovulation.…”

Section: Introductionsupporting

confidence: 53%

Orally Active Oestrogens and Progestins in Prevention of Pregnancy in Rats

Banik¹,

Revesz²,

Herr³

1969

Reproduction

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Summary. Orally active synthetic oestrogens and progestins were studied in tests to prevent pregnancy in rats. By daily administration the contraceptive effect of ethynyloestradiol and a new oestrogen, 17\g=a\-[3-furyl]-estra-1,3,5(10),7-tetraene-3,17-diol 3-acetate (AY-11483), was potentiated by three progestins, namely, chlormadinone acetate, 6-chloro-3\g=b\,17\g=a\-dihydroxypregn-4,6-dien-20-one diacetate (AY-11440) and medrogestone. AY-11483 given alone, or together with AY-11440, was more potent in preventing ovulation and implantation than ethynyloestradiol alone or in combination with other compounds. Chlormadinone acetate or AY-11440 alone were completely inactive in all the assays. The mode of action of oestrogen or oestrogen and progestin in the prevention of ovulation and implantation is discussed. In the rat, implantation seems more vulnerable to oestrogens than does ovulation.

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Section: Introductionsupporting

confidence: 53%

Orally Active Oestrogens and Progestins in Prevention of Pregnancy in Rats

Banik¹,

Revesz²,

Herr³

1969

Reproduction

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“…Contrary to the earlier hopes of Rudel et al (1965), it may well be that for a dose of progestogen to be effective as a contraceptive some interference with menstrual regularity and other side-effects have to occur as a result of hormonal changes and sometimes even of inhibition of ovulation. 21 June 1969 .…”

Section: Discussionmentioning

confidence: 74%

“…The problem is to find a dose of some progestogen, if such exists, which will prevent conception without interfering with the menstrual cycle and with the endogenous hormonal pattern. Rudel et al (1965) considered the most promising substances to be the 17a-hydroxyprogestogens, which do not inhibit ovulation in the doses at present used for contraception. These substances have strong progestational and antioestrogenic activity and might be expected to have a maximum effect on the endometrium and cervical secretions.…”

mentioning

confidence: 99%

Preliminary Evaluation of Four Oral Contraceptives Containing only Progestogens

Mears¹,

Vessey²,

Andolsek³

et al. 1969

BMJ

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Summary: One hundred and seventy-five women took part in a comparative clinical trial of four progestogen-ouly oral contraceptives and were followed for either a year or until treatment was discontinued. Megestrol acetate 0-25 mg. was found to be a very ineffective contraceptive, 21 out of 43 women becoming pregnant. One, three, and four pregnancies occurred during treatment with norethisterone acetate 0'3 mg., norgestrel 0.05 mg., and chodinone 0-5 mg., respectively, corresponding to pregnancy rates of 4, 9, and 12 per 100 woman-years of use.All three effective progestogens were very much less acceptable than modern low-dose combined oral contraceptives. Discontinuation of treatment for medical reasons (particularly menstrual disturbances) during the course of only one year affected 24% receiving norethisterone acetate, 38% receiving norgestrel, and 46% receiving chlormiinone.

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“…One approach has been the utilization of continuous low-dose progestin which has been reported to have an acceptable degree of effectiveness [1][2][3]. It has been shown that continuous administration of 0.5 mg of chlormadinone acetate is an effective contra ceptive agent, and it has been suggested that it apparently does not impair ovulation in the majority of individuals receiving this medication [4][5][6].…”

mentioning

confidence: 99%

Regulation of Human Gonadotropins

Jaffe¹,

Midgley²,

Goebelsmann³

et al. 1970

Gynecol Obstet Invest

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Serum LH, FSH and progesterone concentrations and urinary pregnanediol excretion were quantitated in 5 regularly menstruating women who received 0.5 mg chlormadinone acetate for periods ranging from 51 to 60 days. These gonadotropic hormone and steroid hormones were also measured during the months before and after medication administration. An additional group of 5 women were studied who had been receiving 0.5 mg chlormadinone acetate continuously for at least 6 months prior to having hormone determinations performed, and who continued on this regimen during the entire study period. All of these subjects had serum LH and FSH determinations, and 4 had progesterone measurements performed for 22, 29, 30, 34 and 60 days. In the ‘short-term studies’, while receiving chlormadinone acetate, a typical surge of neither LH nor FSH was observed. However, 4 of the 5 subjects demonstrated atypical, multiple elevations of baseline concentrations of LH at varying times, but usually at the middle of the treatment cycles. Concomitant rises in FSH were not observed. The quantities of pregnanediol excreted during the latter half of treatment cycles were below values normally seen during the luteal phase. During the first treatment cycle, only 1 subject had a relatively normal luteal phase progesterone profile. The concentrations in the other subjects were only slightly elevated, with peak levels between 3 and 4 ng/ml. During the second treatment cycle, 2 of the 4 subjects in whom progesterone determinations were performed had elevated values compatible with normal luteal phase concentrations. Biphasic basal body temperatures were observed in 3 of the 10 treatment cycles. In the ‘long-term studies’, no ‘typical’ LH or FSH profiles were observed. FSH concentrations were frequently elevated for extended periods, and were usually higher than LH concentrations. In only 1 of the subjects was a typical luteal phase elevation in progesterone concentration observed. These data indicate that, unlike other synthetic progestogenic and estrogenic steroids, marked variability in the profiles of the hormones studied is observed in the presence of 0.5 mg chlormadinone, and that typical luteal phase progesterone concentrations may occur in the absence of an antecedent gonadotropin surge.

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The Role of Progestogens in the Hormonal Control of Fertility

Cited by 92 publications

References 8 publications

Orally Active Oestrogens and Progestins in Prevention of Pregnancy in Rats

Orally Active Oestrogens and Progestins in Prevention of Pregnancy in Rats

Preliminary Evaluation of Four Oral Contraceptives Containing only Progestogens

Regulation of Human Gonadotropins

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