Dr. Ron’s Research Review – January 15, 2014

© 2014

This week’s research review focuses on progesterone for uterine fibroids.

Despite the prevalence of uterine leiomyomas in women and the degree to which the leiomyoma cause morbidity, relatively little is known about this disease. (Kim and Sefton 2012)

Progesterone has a complex relationship with uterine fibroids, and may have dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival. (Kim and Sefton 2012) (Ishikawa, Ishi et al. 2010) (Maruo, Ohara et al. 2004)

Lipshutz demonstrated that progesterone administered to guinea pigs prevented formation of tumors that had been induced by estrogen. In 1946, Goodman reported six cases of clinically diagnosed uterine fibroids that regressed after using progesterone therapy. (Goodman 1946) (Lipshutz 1942) (Lipshutz and Vargus 1941)

Dr. Ron


Articles

Progesterone therapy in uterine fibromyoma

         (Goodman 1946) Download

IN A STUDY on experimental fibromyomas and their prevention, Lipschiitz and Inglesias (6) showed that subserous uterine fibromyomas and extragenital subserous fibromyomas in the abdominal cavity can be produced in guinea pigs subjected to prolonged treatment with estrogens. All estrogens, natural and artificial, free and esterified, were shown to be tumorigenic. Under certain conditions of treatment with estrogens a female guinea pig only rarely escaped the development of abdominal fibromyomas. Continuous action of the hormone was an essential factor. When a period of one week of injections was followed by a period of two weeks without injections no fibromyomas were produced even after a year of such treatment. On the other hand, minute quantities of free estradiol, insufficient to produce fibromyoma when given three times weekly by subcutaneous injection, proved highly active when absorbed from a subcutaneously implanted pellet. It was suggested that the tumorigenic action of estrogens in the normal organism is controlled by the sexual cycle with the alternation of high and low level phases of blood estrogen and by inactivation or elimination of the hormone.

Prevention Of Experimental Uterine And Extrauterine Fibroids By Testosterone And Progesterone

         (Lipshutz and Vargus 1941) Download

ACCORDING TO LIPSCHÜTZ, VARGAS AND RUZ (I) uterine and extrauterine fibroids which are so easily induced by a prolonged treatment with estrogens in the guinea pig, can be partially prevented if testosterone is injected simultaneously with the tumorigenic quantities of estradiol. LipschÜtz, Murillo and Vargas (2, 3) gave evidence that progesterone also is able to prevent these experimental fibroids. The antitumorigenic action of testosterone became manifest when the proportion of the esterified estradiol and the esterified testosterone was no less than 1:22; in other experiments proportions of 1:50 and more were made use of. The preventive action of progesterone was observed with quantities of the latter 150 times greaterthan those of estradiol. On account of the small number of our experiments and of the considerable individual variations as to the degree of the conjunctive tumoral reaction we raised the objection that the results may have been due to chance.

Experimental fibroids and the antifibromatogenic action of steroid hormones

         (Lipshutz 1942) Download

Not being a gynecologist or an obstetrician, I feel obliged to offer my apologies for presenting a paper on experimental fibroids and their prevention in this section inspired by practical aims which might be of use to suffering womanhood. Let me express my apology in the words of a great American. Almost one hundred and fifty years ago, a few days before the final treaty of independence with England was signed, Franklin saw in Paris the first balloon ascension. The spectators argued about the utility of the experiment. What good, some skeptic asked, could a balloon be? What good, Franklin replied, was a newborn baby?

Obstetricians and gynecologists will be the first to appreciate or not the claims of the scientific newborn babies, which experimental fibroids and antifibromatogenic steroids are.

Subserous uterine fibroids were first elicited in the United States by W. O. Nelson in a number of guinea pigs


References

Goodman, A. L. (1946). "Progesterone therapy in uterine fibromyoma." J Clin Endocrinol Metab 6: 402-8. [PMID: 20983484]

Ishikawa, H., K. Ishi, et al. (2010). "Progesterone is essential for maintenance and growth of uterine leiomyoma." Endocrinology 151(6): 2433-42. [PMID: 20375184]

Kim, J. J. and E. C. Sefton (2012). "The role of progesterone signaling in the pathogenesis of uterine leiomyoma." Mol Cell Endocrinol 358(2): 223-31. [PMID: 21672608]

Lipshutz, A. (1942). "Experimental fibroids and the antifibromatogenic action of steroid hormones." JAMA 120(3): 171-175. [PMID:

Lipshutz, A. and L. Vargus (1941). "Prevention Of Experimental Uterine And Extrauterine Fibroids By Testosterone And Progesterone." Endocrinology 28(4): 669-675. [PMID:

Maruo, T., N. Ohara, et al. (2004). "Sex steroidal regulation of uterine leiomyoma growth and apoptosis." Hum Reprod Update 10(3): 207-20. [PMID: 15140868]