Open AccessOVULATION INHIBITION WITH DIFFERENT DOSES OF LEVONORGESTREL * AND OTHER PROGESTOGENS: CLINICAL AND EXPERIMENTAL INVESTIGATIONS
Author(s) -
Spona J.,
Schneider W. H. F.,
Bieglmayer Ch.,
Schroeder R.,
Pirker R.
Publication year - 1979
Publication title -
acta obstetricia et gynecologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.401
H-Index - 102
eISSN - 1600-0412
pISSN - 0001-6349
DOI - 10.3109/00016347909157223
Subject(s) - levonorgestrel , endocrinology , medicine , ovulation , hormone , basal (medicine) , luteinizing hormone , chemistry , population , environmental health , family planning , insulin , research methodology
. Model systems were evaluated, which can be used to determine biological activities of progestogens at various cell levels of the anterior pituitary gland. in addition, various progestogens at different dose levels were tested in females to evaluate the ovulation inhibition dose. the association of progestogens with the cytosol receptor of the adenohypophysis of the rat was studied in vitro. Sucrose gradient centrifugation analysis revealed material sedimenting in the 4‐5 S and 6‐7 S region, resp., and both binding proteins were found to specifically bind progestogens. a small displacement by cortisol was observed in the 4‐5 S area. Relative affinity constants were estimated for various progestogens by incubation of cytosol samples with radioactive labeled progestins, and a close correlation between affinity and biological activity was recorded. Adult female rats seven days after castration were used to study the influence of various progestogens on LH‐RH stimulated gonadotropin release. Levonorgestrel was found to augment LH‐RH provoked LH release in vivo, whereas both basal as well as LH‐RH stimulated FSH serum levels were noted to be impaired at higher doses of the steroid. Similarly, δ 15 ‐levonorgestrel was observed to increase the response of LH to LH‐RH. on the other hand, δ 15 ‐levonorgestrel greatly augmented basal as well as LH‐RH induced FSH serum levels up to a dose of 10 μg. At 100 μg of δ 15 ‐levonorgestrel FSH serum levels were suppressed again. But, only 1/3 of the levonorgestrel dose was necessary to produce these effects, i. e. δ 15 ‐levonorgestrel was found ca. 3‐times more potent than the native progestogen. Experiments performed in a cell culture system of anterior pituitary cells revealed an impairment of LH‐RH stimulated gonadotropin release. LH and FSH release was suppressed to 40 and 50%, resp., at ED 50 of LH‐RH in the presence of 3×10 −8 M levonorgestrel. LH and FSH release was reduced to 50 and 70%, resp., when anterior pituitary cells were incubated with LH‐RH in the presence of 3×10 −8 M δ 15 ‐levonorgestrel. Thus, cell culture experiments also suggested that the potency of the δ 15 ‐derivative of levonorgestrel was ca. 3‐times more potent. Analysis of patterns of cervical scores and karyopyknotic index as well as of serum levels of 17β‐estradiol, progesterone, LH and FSH revealed a borderline ovulation inhibition dose of levonorgestrel and δ 15 ‐levonorgestrel at 50 and 30 μg, respectively. Cyproterone acetate, which is used in an oral contraceptive to treat acne and hirsutism was found to inhibit ovulation at a borderline dose of 1 mg. the present data combine to suggest that all model system are efficient to evaluate new progestogens, and that δ 15 ‐levonorgestrel exerts a some 3‐times greater biological activity than levonorgestrel itself. Thus, a dose reduction of the progestogen component in oral contraceptives seems to be possible.