John McLean Morris

The syndrome of testicular feminization in male pseudohermaphrodites

Abstract There is a clinically recognizable syndrome found in patients who are essentially normal-appearing women, but who have undescended testes in place of ovaries. The most significant features are: 1.1. Female habitus, breast development, and other secondary sex characteristics. 2.2. Scanty or absent axillary or pubic hair in most cases. 3.3. Female external genitals, with a tendency to underdevelopment of labia, and a blind-ending vagina. 4.4. Absence of internal genitals except for rudimentary anlage and for gonads which may be located intra-abdominally or along the course of the inguinal canal. 5.5. Gonads histologically consistent with undescended testes. 6.6. Urinary excretion studies have suggested such testes produce estrogen and androgen. Elevated urinary gonadotropins have also been found.

Interception: The use of postovulatory estrogens to prevent implantation

Abstract The administration of high dosages of estrogen in the postovulatory period appears to be effective in lowering pregnancy rates following mid-cycle exposure to the 0.3 to 0.03 per cent range. While nausea is encountered in approximately half the patients, no serious side effects have been noted except for one case of acute pulmonary edema. The incidence of ectopic pregnancy appears to be elevated. No fetal abnormalities were noted in infant macaque monkeys born when marginal maternal doses were given.

Compounds interfering with ovum implantation and development. 3. The role of estrogens.

The administration of ORF-3858 and certain estrogens postcoitally in the primate appears to prevent implantation of the ovum.Abstract The administration of ORF-3858 and certain estrogens postcoitally in the primate appears to prevent implantation of the ovum.

Compounds Interfering with Ovum Implantation and Development: II. Synthetic Estrogens and Antiestrogens

Studies were carried out on a group of synthetic estrogens and antie strogens (clomiphene U-11555A a 23 diphenylindene derivative U-1110 0A a dihydronaphthalene and ORF-3858 2-methyl-3-ethyl-4-phenyl-delta 4-c yclohexenecarboxylic acid) to determine their effects as postcoital contraceptive agents in the rabbit and macaque monkey. Most proved effective with direct action on the implantation site in the rabbit but only ORF-3858 showed no evidence of teratogenicity and was found effective postcoitally in the primate.

The Estrogenic Activity of Postcoital Antifertility Compounds

The postcoital antifertility activity of 17 natural and synthetic steroidal and non-steroidal compounds was evaluated in the rabbit. The estrogens tested (estrone ethinyl estradiol stilbestrol mestranol estradiol-17beta) were the most effective inhibitors of implantation while ORF-3858 was slightly less effective. RS-2196 and RS-229 had effects similar to those found in rats and were in the range of effectiveness of clomiphene and U-11100A. U-11555A had considerably less effect. Both norethindrone (less than 2% estrogen) and Sch-10015 inhibited implantation. Similar doses of testosterone and dihydrotesterone also inhibited implantation. Progesterone and chlormad inone acetate however failed to prevent implantation. All other compounds had sufficent uterotrophic activity to at least double uterine weight. Those compounds that were effective appeared to act directly on the endometrial implantation site.

Postcoital antifertility agents and their teratogenic effect

Abstract Of agents effective in preventing implantation or interfering with embryonic development in the rabbit, teratogenicity has been noted with clomid, U11, 100A, U11, 555A, parahydroxypropiophenone, vinblastine, colcemide, BW 57-323H, and 6-azauridine. No teratogenicity (other than virilization with androgens) has been noted with any steroid, with stilbestrol, or with ORF-3858 in either the rabbit or the macaque monkey. Post facto contraception has certain obvious advantages. Precoital techniques involve some waste of contraceptive effort, require premeditation, often have unwanted side effects, may have anti-esthetic and anti-erotic aspects, and are not as yet infallible. The sex act has a degree of spontaneity, and were a perfect contraceptive method at hand, there would always be some individuals who fail to plan ahead. In addition to the requirements of effectiveness and lack of toxicity or undesirable side effects, postcoital contraception involves an additional serious hazard. This danger is that the agent when taken in marginal doses or at marginal times may prove teratogenic.

Effects of postovulatory estrogen on progesterone and prostaglandin F levels ih the monkey

Abstract Estrogen administration during the luteal phase of the menstrual cycle resulted in rapid decline of progesterone levels in the peripheral plasma of 13 out of 16 cycles in macaque monkeys. In most instances, values returned to normal whether or not estrogen was continued. In more than half the animals, there was also a rise in plasma prostaglandin F.

Ovarian carcinoma: The problems of staging and grading

Abstract A review of 148 cases of primary ovarian cancer is presented. The data have been analyzed on the basis of information collected from a review of the literature. Studies of the histology of these tumors indicated the following: 1. 1. Survival figures based on histogenetic classifications were of dubious value. This was in part due to the large number of undifferentiated tumors that were unclassifiable. 2. 2. Classifications based on tumor grade provided a satisfactory separation of prognostic groups. 3. 3. Histologic grade appeared to remain relatively constant in a given tumor. 4. 4. Cell differentiation provided better criteria of degree of malignancy than did the ever-all structure of the tumor. 5. 5. Stromal invasion was not of statistical value in this study, as it occurred in over 85 per cent of the specimens examined. Tabulation of cases on the basis of anatomic spread indicated: (1) extent of spread furnished significantly different prognostic groups; (2) unilateral tumors, whether confined or whether complicated by excrescences, rupture, or adhesions, appeared to have a better prognosis than corresponding bilateral tumors; however, there appeared to be no prognostic difference between unilateral or bilateral tumors when spread beyond the ovary had occurred; and (3) although ascites was associated with more advanced tumors, it did not appear to affect the prognosis in cases with similar anatomic spread. Attempts to use any of the several published staging methods demonstrated the current lack of a satisfactory staging system. Because of the multiple variables involved, conclusions regarding therapeutic modalities could not be made in this study.

Mechanisms involved in progesterone contraception and estrogen interception

Abstract While there are certain differences between biological responses to C-21 progestogens and the 19-norsteroids, precoital progestogens in general interfere with sperm transport, fertilization, and ovum transport. A 36 hour interval was required to achieve 100 per cent precoital contraceptive effectiveness in the rabbit. At marginal doses or timing, blastocyst degeneration may occur, and with large doses of progesterone at the time of coitus some teratogenic effects were noted. Postcoital estrogen is associated with lowering of plasma progesterone levels. Concomitant progesterone administartion, however, does not completely reverse the interceptive effect of estrogen. Direct effects on the endometrium include disintegration of the nucleolar channel system, retention of glycogen in endometrial glands, decreased alkaline phosphatase, and lowered endometrial carbonic anhydrase. The latter may be the basic mechanism of action.

Effect of Postcoital Estrogen on Uterine Carbonic Anhydrase

To study the correlation of the antifertility effect of estrogen with uterine carbonic anhydrase levels stilbestrol was administered intramuscularly to female rabbits on various days following mating. The animals were sacrificed at various intervals following administration of the drug. Their uteri were removed and examined. They were then assayed for carbonic anhydrase (CAH). In a control group uterine CAH levels rose on the third day after mating. In animals receiving .06-1.0 mg/kg doses of stilbestrol on Day 1 or on Days 1-3 following mating a reduction was seen in CAH on Days 4-6. In rabbits treated on Day 1 a drop was also noted on Days 7-10. Stilbestrol given in a single dose of 1 mg/kg on Day 1 3 5 or 7 had no significant effect on CAH levels when the rabbits were examined within 24 hours. It was noted that rabbits who received 1 mg/kg doses often had pyometra and hemorrhage into the uterine wall after a period of 3 days. At all doses administered early during the postcoital period pregnancy was disrupted.