Gonadotropins and Steroid Hormones

Carl Gemzell, M. D.
Professor, Department of Obstetrics and Gynecology, Downstate Medical Center, State University of New York, Brooklyn, New York

Endometriosis, Aspects and Proceedings of a Symposium
Saint John's Hospital and Health Center, Santa Monica, California
Editor: J.J. Marik

Going through the literature, I was surprised to find that few studies have been done on gonadotropins and ovarian steroids in patients with endometriosis. On the one hand, one would expect that such studies should have been done, as endometriosis very often affects the ovaries, but on the other hand it is a well-known fact that young women have regular ovulatory periods, even when their ovaries have been almost totally destroyed by endometriosis. Another reason for this apparent lack of interest may be that endometriosis often is an accidental finding, so that treatment has been initiated before hormonal assays were started. It is also surprising that a great number of hormonal treatments of endometriosis have been done without knowing their effect on the anterior pituitary and the ovaries.

During the last few years, sensitive and specific radioimmunoassay methods have been available for the determination of protein hormones and steroids in blood or urine. It is now possible to follow closely changes in the levels of the two gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), throughout the menstrual cycle, and their effect on the ovary as indicated by levels of estrogen and progesterone in blood or urine. Results from many different laboratories usually show the same pattern which indicates that the techniques now are well established and performed.(1)

The patterns of FSH, LH, estrogen and progesterone during a normal menstrual cycle and the positive and negative feed-back mechanisms of the ovarian steroids are by now well-known and there is no reason to repeat them here. It is a close reciprocal relationship between the pituitary gonadotropins and the gonadal steroids, except at midcycle and at the menopausal age. The increase in LH at midcycle is several times that of FSH, while the rise in FSH during the menopause is more pronounced than the rise in LH. This indicates that FSH and LH exist as separate entities with different behavior during various physiological conditions, that different control mechanisms are active in their release and that stimulation or inhibition can be induced separately to one and not necessarily to the other.

When the levels of estrogen production of normally ovulating women during the menstrual cycle have been compared, great variations from one individual to another were found. The total amount of estrogen excreted during the last 20 days of the cycle has varied between 100 µg and 650 µg. Individual variations between cycles were small while variations between different women were quite large. Differences in progesterone production duringthe same period of the cycle were less pronounced.(2) Therefore, it may be possible to differentiate between hyperestrogenic versus hypoestrogenic women, a finding which may have some implication related to endometriosis.

How does therapy with estrogen, progestin or a combination of the two affect the anterior pituitary and the ovaries of patients with endometriosis? We do not really know, but suspect that they may react in the same way as in women without endometriosis. Ovulation may or may not be inhibited and the menstrual cycle regular or abolished.

The combined treatment with estrogen-progestin will abolish the LH peak at midcycle and decrease the basic levels of FSH and LH release from the pituitary. Estrogen alone (in sufficient dosage) will also decrease the basic release of both FSH and LH and abolish the midcycle peak of LH. Progestin alone may or may not affect the midcycle peak of LH, while leaving the basic levels of FSH and LH unaffected. This may cause abnormal ovarian response with elevated levels of estrogen for long periods of time as well as abnormal corpus luteum function.(3) In patients with endometriosis this may have a deleterious effect on the growth and spread of the disease. A chemical substance like danazol (Danocrine,® Winthrop), which seems to inhibit both FSH and LH release, is therefore of great advantage in the treatment of endometriosis, especially as it has negligible effects.

References

1. Wide, L., Nillius, SJ., Gemzell, C. and Roos, P. (1973): Radioimmunosorbent assay of follicle-stimulating hormone and luteinizing hormone in serum and urine from men and women. Aria Endocrinol. Suppl. 174.
2. Johansson, E.D.B., Wide, L. and Gemzell, C. (1968): Luteinizing hormone (LH) and progesterone in plasma and LH and oestrogens in urine during 42 normal menstrual cycles. Aria Endocrinol. 68:502-512.
3. Larsson-Cohn, U., Johansson, E.D.B., Wide, L. and Gemzell, C. (1970): Effects of continuous daily administration of 0.5 mg of norethindrone on the plasma levels of progesterone and on the urinary excretion of luteinizing hormone, pregnanediol and total oestrogens. Acts Endocrinol. 03:216-224.

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