The Clinical Use of Pituitary Gonadotrophins in Women

Abstract

On 22nd January 1926, in lectures to the`Gesellschaft f\l=u"\rGeburtshilfe und Gyn\l=a"\kologie zu Berlin', Zondek (1926) and Aschheim (1926) first made public the results of experiments on the intact immature mouse which demonstrated that the anterior pituitary contained substances which could stimulate the ovaries. They called the anterior pituitary`M otor der Sexualfunktion'. As with many of the most brilliant advances in medicine, their findings were confirmed by simultaneous but independent experiments on intact animals and hypophysectomized rats by Smith (1926) and Smith & Engle (1927) at Stanford University, California. Zondek and Aschheim ultimately suggested that there were two gonadotrophic substances in the anterior pituitary, one responsible for follicular development and the other for corpus luteum formation after follicular rupture. They called them`H ypophysenvorderlappenhormon A, (hvh-a) and`hvh-b'. These concepts are very similar to present-day teaching about the mechanisms involved in ovulation. It is now confirmed that there are two separate gonadotrophic substances: follicle-stimulating hormone (fsh) and luteinizing hormone (lh) also known as interstitial cell stimulating hormone (icsh). At the onset of a menstrual cycle, under the influence of fsh from the anterior pituitary a number of follicles begin to develop and secrete oestrogen which causes endometrial proliferation. All but one of the follicles, for reasons unknown, become atretic. At about mid-cycle, under the added influence of a surge of lh, the favoured fsh-primed follicle ruptures with discharge of an ovum. The ruptured follicle is then transformed into a corpus luteum in which progesterone and small amounts of oestrogen are formed. The progesterone leads to secretory changes in the endometrium. In gynaecological practice human gonadotrophins are almost exclusively used for attempts to induce ovulation by imitating the sequential release of fsh and lh from the anterior pituitary. In women there is no evidence for the dependence of the corpus luteum on a third hormone, prolactin or luteotrophic hormone (lth), as is the case with experimental animals.

Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT

“…However, fertility endocrinology was still on its way to establish its worth with limited therapeutic application until the middle of the century. The discovery of human chorionic gonadotropin (hCG) by Carl Gemzell was a big leap in the modern management of infertility, as it lead to the development of routinely used pregnancy test and ovarian stimulation, which is the cardinal step in assisted reproductive technology (ART) (Gemzell, 1962, Gemzell, et al, 1966. Later, in 1978, Professor RG Edwards and his team successfully recorded the birth of the first IVF baby in England.…”

Rooted in pre-assisted reproductive technology times menotropins are still used today: a narrative review of literature

“…Stemming from the seminal work of Zondek et al (8,9), it was determined that the pituitary produced hormones that control gonadal function in males and females, FSH and LH. Follicle-stimulating hormone destined for therapeutic use, namely induction of ovulation, was initially obtained from pituitary extracts (10). However, it soon became evident that it was both safer and easier to extract gonadotropins form urine of menopausal women, a product identified as human hMGs (11).…”

The Follicle-Stimulating and Interstitial Cell-Stimulating Activities of Pregnant Mare Serum Gonadotrophin Compared With Those of Other Gonadotrophins

“…Table 1 shows the ratio of follicle-stimulating to interstitial cell-stimulating activity of PMSG, hypophysial FSH, HMG and HCG preparations, including the fiducial limits for the assays (J0%). ICSH were obtained: (1) PMSG~0-1 (n = 195); (2) hypophysial porcine FSH > 10-0 (n = 113); (3) hypophysial human FSH~2 (n = 88); (4) HMG~1-0 (n = 89) and (5) Gemzell, Roos & Loeffler (1966) recommended the combined therapy with hypo¬ physial human FSH + HCG for women with secondary ovarian insufficiencies. FSH:i.u.…”

“…FSH:i.u. Meanwhile Groot-Wassink (1967) has also reported more than 20 pregnancies in women with amenorrhoea or anovulatory cycles after the administration of porcine FSH + HCG in doses recommended by Gemzell et al (1966) for human FSH + HCG. The favourable therapeutic results have often been assumed to be caused by a speciesspecific action of the human FSH preparations.…”