Certainty? Maybe, Maybe Not: 1950 to 2000
John K. Crellin in A Social History of Medicines in the Twentieth Century, 2020
The "improvements" noted were nonestrogen or low-dose estrogen products—the latter in fact having been used more widely in Britain than in the United States and Canada in the 1960s.197 Uncertainties, however, remained, as reflected in 1970 when Time magazine told readers about a new progestogen-only product: Chlormadinone differs from conventional forms of the Pill in two vital respects: 1) it consists simply of a synthetic analogue of the hormone progesterone and contains none of the estrogen that has been implicated in clotting disorders among Pill users ... 2) it is taken every day of the year, and not on the 21 -days-on, seven-days-off schedule of other forms of the Pill. Like the other versions—and, in fact like all other potent medications—chlormadinone has its drawbacks. The failure rate, judged by unwanted pregnancies, is slightly higher than with other pills, and some women complain of irregular menstrual bleeding.198 This cautious optimism, reflecting authoritative medical opinion at the time, was fair comment given the existing state of knowledge.199
Drugs in Pregnancy and Lactation
A. S. Curry, J. V. Hewitt in Biochemistry of Women: Clinical Concepts, 1974
A variety of methods of oral contraception are now available which may be categorized as follows: (1) the combination estrogen-progestogen pill; (2) the sequential method, using estrogen (day 5 to 25) to inhibit ovulation and progestogen (the last 5 days) to initiate shedding of the endometrium with normal menstruation; and (3) low-dosage progestogen administered continuously. These various methods employ the synthetic steroids mestranol or ethynylestradiol as estrogens and chlormadinone acetate, medroxyprogesterone acetate, norethisterone, or norethynodrel, etc. as progestogens (see Figure 3).
Neurodevelopmental disorders in children exposed in utero to synthetic progestins: analysis from the national cohort of the Hhorages Association*
Published in Gynecological Endocrinology, 2019
Marie-Odile Soyer-Gobillard, Laura Gaspari, Philippe Courtet, Mauricette Puillandre, Françoise Paris, Charles Sultan
From the questionnaires completed by the families and returned to the Hhorages Association, it appears that one or several progestins were prescribed and administered to pregnant mothers as shown in the numerous conserved medical prescriptions. The prescribed pharmaceuticals were: 17α-hydroxyprogesterone caproate (synthetic progestin, SP): 32 (Note: withdrawn in 2000 but re-authorized in 2011), 17α-hydroxyprogesterone heptanoate (SP): 10 (Note: withdrawn in 2002), chlormadinone acetate (SP derived from hydroxyprogesterone): 11 (Note: withdrawn on 1970), dydrogesterone (6-dehydroprogesterone, synthetic isomer of progesterone): 4 (Note: against total indication for pregnant women; not withdrawn), ‘natural progesterone’ (derived from soybean, micronized): 4 (Note: not withdrawn), Norethisterone Base (SP): 1 (Note: against total indication for pregnant women; withdrawn in 1998). Total: 62.
Primary choice of estrogen and progestogen as components for HRT: a clinical pharmacological view
Published in Climacteric, 2022
In our recommendations (Table 6) we have considered the different tolerability of the various progestogens. For example, progesterone and its derivatives present a mostly higher tolerability and are mostly neutral in their metabolic and vascular effects (higher doses are possible to ensure endometrial safety) in contrast to norethisterone and its derivatives, and also considering the lower endometrial efficacy especially of progesterone with the consequence that higher doses are possible, even though this is certainly not needed in all patients. Especially high dosages of progesterone have been used in reproductive medicine (e.g. 800 mg/day) without a high frequency of side effects (with the exception of bloating due to mineralocorticoid metabolites), the strong sedative effect not being a disadvantage for HRT (if applied during evening). For the progestogen challenge test, in earlier years we often used oral NETA (1–2 mg/day) due to its strong endometrial efficacy, but in our countries this is no longer available. Alternatively, chlormadinone acetate (4–6 mg/day), dienogest (2–4 mg/day) or dydrogesterone (10 mg/day) can be recommended. For this test we would not like to recommend progesterone.
Effects of progestin-only contraceptives on the endometrium
Published in Expert Review of Clinical Pharmacology, 2020
Carlo Bastianelli, Manuela Farris, Vincenzina Bruni, Elena Rosato, Ivo Brosens, Giuseppe Benagiano
In 1967, Martinez-Manautou et al. [37] presented their first experience with what became known as the ‘Minipill’ (or progestin-only pill, POP), a new method aimed at producing a local antifertility effect by modifying both the endometrium and the cervical mucus, without suppressing the hypothalamic-pituitary-ovarian axis. They used daily 0.5 mg chlormadinone acetate (CMA), first from day 5 to 25, and later without interruption, with encouraging results. In a further report, Martinez-Manautou [38] summarized information, based on 1070 biopsies, on the endometrial effects of the new method; a secretory endometrium was observed in 67.4 and 79.7% of all samples, depending on timing. This suggested no major interference with glandular development.
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