E. C. Hamblen

Dysmenorrhea and ovulation: correlation of the effect of estrogen therapy on pain the endometrium and the basal body temperature.

Treatment of dysmenorrhea by the suppression of ovulation with estrogen therapy is reported. 178 cycles of treatment were studied in 30 patients. The correlation of dysmenorrhea and ovulation was studied by endometrial biopsy and basal body temperature (BBT). 82 biopsies and 11 temperature records were obtained from 5 patients. In 50 baseline (untreated) cycle 46 progestational and 4 estrogenic endometriums were seen. Pain was associated with progestational biopsies. Of 32 biopsies taken after treatment 21 were progestational and 11 estrogenic. An ovulatory BBT was also associated with a progestational endometrium and with pain. In 91 cycles treated with less than 25 mg of remarin or less than 20 mg of diesthylstilbestrol (DES) 25.3% were totally relieved. In 53 cycles treated with 25 mg remarin or 20 mg DES 49.1% were totally relieved. In 23 cycles treated with 75 mg and 60 mg respectively 78.3% were totally relieved. All failures were associated with a progestational endometrium. In order to establish the optimal dosage for individual patients it is advisable to follow treatment with endometrial biopsies and BBT. Gross menstrual disturbances were absent during treatment.

Characteristics of the normal menstrual cycle.

Previous studies which have shown that the lengths of apparently normal menstrual cycles vary widely and that absolute regularity in the individual patient is exceptional have not eliminated anovulatory cycles patients with subtle endocrine disturbances and such lesser disturbances as travel monor illnesses or alterations of working hours. Variable schedules make data based on nurses especially suspect. In this study 109 women were carefully selected and all cycles showing late hours restless sleep travel febrile illnesses and other disrupting factors were eliminated. Of the 524 recorded cycles 500 or 95.4% were ovulatory 13 or 2.5% were anovulatory and 11 or 2.1% were indeterminate. All 58 biopsies from cycles with ovulatory temperature patterns revealed progestational endometriums. Of the 500 ovulatory cyc les 0 were shorter than 19 days; 1 was longer than 60 days; 3.2% were 19-22 days; 21.4% were 23-25 days; 53.6% were 26-29 days; 17.8% were 30-36 days and 4% were longer than 36 days. More than 1/2 were 26-29 days and 92.8% fell within the 23-26 day interval. Comparison with the data of others shows that when anovulatory cycles are eliminated short cycles (less than 19 days) apparently disappear from the curve. Studies with a larger number of mature women have fewer anovulatory cycles. In 79.6% of the women the estrogenic phase was 10-16 days long. In 1.9% it was less than 10 days in length but in 15.6% it was 17-25 days and in 2.9% longer than 25 days. Except for 1 progestation rise which was only 5 days long the progestational phase was 8-19 days long. 69.5% showed progestational phases of 11-14 days 94.0% of 10-16 days 1.8% less than 10 days and 4.3% 17-19 days. This confirms the belief that the unusual length of the ovulatory cycles results from a longer estrogen phase. In 68.4% of patients bleeding was 3-5 days in duration and in 95.4% 3-7 days. The mean temperature differential between pre- and pos tovulatory phases is often relatively small (.2-.5 degrees F). In 78.9% the rise was .6-.9 degrees F. This emphasizes the value of recording the temperature in degrees Fahrenheit on a relatively large scale rather than using a small scale or degrees Centrigrade.

A study of ovaries following preoperative administration of an extract of pregnancy urine

Abstract 1. 1. A study of ovarian tissue from twenty-four patients following preoperative administration of APL/PU is detailed. 2. 2. Primordial follicles are not affected apparently by such administrations. 3. 3. Degenerative changes apparently resulting from follicle stimulation are described. 4. 4. The end-result of these changes appears in many instances to be follicular cysts, with active granulosa and fairly well preserved ova, and surrounded by a proliferated theca interna with prominent theca lutein cells (theca-lutein cysts) and with increased thecal vascularization. 5. 5. Some evidence is adduced that persistency of preformed corpora lutea may result from such administrations. 6. 6. Attention is called to the apparent difference in response in the ovaries of the younger and older patients with hyperplasia of the endometrium. 7. 7. In general, it is believed that ovulation is not induced by such administrations. 8. 8. The possible action of these extracts in many respects is more typical of the gestational cycle than the menstrual cycle. 9. 9. One should probably expect no material qualitative or quantitative difference in the changes in these ovaries from those of ovaries in pregnancy. 10. 10. One is led to question seriously the clinical value of such action on the ovaries of the nonpregnant woman. 11. 11. Such changes as described are probably temporary in nature and it may be that no permanent damage results.

Some clinical observations on the endocrinology of abortion

Abstract Some concepts of the hormonology of abortion have been reviewed and studies of progestin metabolism in patients with histories of repeated abortions have been reported. The following observations seem warranted from our studies: 1. 1. As a rule, pregnanediol titers tend to fall prior to abortion. This fall may be abrupt or gradual. 2. 2. During the course of pregnancy prior to the onset of abortion titers may be normal or low. 3. 3. Patients may threaten to abort when pregnanediol titers are normal. 4. 4. Intensive therapy with progesterone, alone or combined with estrogens and chorionic gonadotropins, fails to elevate low pregnanediol titers and to prevent abortion. 5. 5. There is a likelihood that large doses of progesterone may precipitate abortion by depressing the metabolism of intrinsic progestin. 6. 6. Progesterone therapy may interfere with the therapeutic efficacy of thyroid substance in preventing abortion in hypothyroidism. 7. 7. Any beneficial effect which therapy with progesterone possesses in the treatment of habitual abortion cannot be explained upon the basis of its complementing deficits in progestin-pregnanediol metabolism.

Male pseudohermaphroditism: some endocrinological and psychosexual aspects.

Abstract Studies of eleven male pseudohermaphrodites from the standpoint of histopathology of the testes, levels of urinary gonadotropins and 17-ketosteroids, and psychosexual orientation have been reported. Particular attention has been paid to those patients with gynecoid psychosexual patterns. The results of castration and estrogenization of these patients have been discussed. Responses of local target organs to estrogen therapy have been considered. Justification for castration of these individuals is presented. The beneficial effects of estrogenization have been discussed. Some of the sociological and medicolegal questions posed by these patients have been considered.

The metabolism and utilization of progesterone given intramuscularly to women

Abstract Studies have been reported upon the endometriotropic responses of 23 patients with functional irregularities of uterine bleeding during 99 of 117 cyclic series of therapy with progesterone alone or combined with estrogens. During 30 cycles of 4 of these patients, and during 10 cycles of an additional group of 3 patients, similarly treated, urinary titers of sodium pregnandiol glucuronide were determined. The endometriotropic data warrant the conclusion that crystalline progesterone, when administered intramuscularly in oil to women with functional irregularities of uterine bleeding, is inefficiently utilized. Six of the 7 patients studied were also unable to utilize efficiently their intrinsic progestin despite the existence of evidence that it was being metabolized normally. The intramuscular administration of crystalline progesterone to these patients resulted not only in no increases in their urinary titers of the pregnandiol-complex but also in apparent decreases. These observations suggest that incomplete metabolism occurred. Some of the various factors which may influence the metabolism and utilization of progesterone are discussed.

Bilateral functioning cystadenofibromas of the ovaries: Report of a case☆

Abstract A case of bilateral cystadenofibromas of the ovaries, apparently producing estrogenic substances, is reported. We have not been able to find a previous report in the English literature of a similar case of bilaterality and estrogenic function.

Effects of estrogenic therapy upon ovarian function

T HE ability of adequate estrogenie therapy to transform normal progestational cycles of women to estrogenic (and presumably anovulatory) ones has been verified in the preceding communication.l It would appear most unlikely that therapy of this kind and order is capable of restoring normal progestational cycles in women with ovarian failure of anovulatory type. An investigation, however, of the end results of estrogenic therapy in association with anovulatory failure seemed advisable for several reasons : (1) to confirm or to deny the dictum that, regardless of our ability to substitute for the endocrine deficienry of ovaries with intrinsic ovarian principles no salvage of physiologic functions, i.e., return of the fertile state, results; and (2) to confirm or to deny the theory that the salvage of ovarian function which has been described as following cyclic estrogenprogesterone therapy in a large group of women with prolonged or excessive estrogenic bleeding results solely from t,he estrogenic fraction of the therapeutic schedule. The commercial availability of a cheap, potent,, and orally active nonhormonal est,rogen (diethylstilbestrol) requires a clear definition of the role of estrogens in the treatment of ovarian failure. Methods Sixteen patients whose ages ranged from 15 to 35 years (average age 21.6 years) were selected for this investigation. These patients had presumed anovulatory ovarian failure predicated upon the occurrence of episodes of estrogenic bleeding. The bleeding cycles were commonly irregular and often of prolonged duration. Each patient selected had received from one to three endometrial biopsies prior to initiation of therapy. Two hormonal estrogens, estriol glucuronidet and estradiol in the form of its benzoatet and dipropionate,§ and an nonhormonal estro*Part I of this article was included in the February issue. ?Estriol glucuronide (emmenin) supplied by Ayerst, Montreal, Canada. McKenna and Harrison.

The assignment of sex to an individual: Some enigmas and some practical clinical criteria

Abstract The truc sex of an individual is not necessarily that which agrees with his or her chromosomes, gonads, hormone production, morphology of the external genitals or that of the internal genitals. After the age of 2½ years, it is definitely the sex of assignment and rearing, fortified by gender role and psychosexual orientation. Eight clinical types of ambiguities of sexing are classified and synopsized with their chromosomal, morphological, and endocrinological characteristies. These types are reconciled with Josts theory of the role of the fetal testis in sex differentiation. Sex chromatin data are of ancillary but not primary valuc in the differentiation of these types. A practical plan for prompt sex assignment at birth is outlined. This is advisable to avoid psychological trauma to parents and to circumvent gossiping of relatives and acquaintances. Surgery and/or endocrine therapy usually are necessary to implement the assigned sex. Parents should understand this plan to complete the sexual development of their “unfinished” baby. Medical, religious, and medicolegal aspects of the implementation of assigned sex are discussed. The assignment and implementation of a practical sex, before gender role complicates matters, should assure individuals with sexual ambiguities of becoming well-oriented, coitally adequate, if not fertile, adults. If sex reassignment becomes necessary, it should be done before gender role is established, a new birth certificate should be filed and all pertinent documents, as wills and insurance policies, altered. When sex is reassigned after gender role is established, psychosexual problems arise and rarely, if ever, is a pervasive, convincing, and unequivocal adaptation to the new sex developed.

Some observations on the gynecic employment of equine gonadotropins

Abstract 1. 1. Equine gonadotropins may stimulate ovaries which possess normal sensitivity to pituitary stimuli. 2. 2. Equine gonadotropins are of value therapeutically in those women whose ovarian failure is due to deficient pituitary function. 3. 3. The effects of equine gonadotropins are often temporary, the pituitary failure and the secondary ovarian failure recurring. 4. 4. This last statement has a bearing upon the handling of pregnancy secured by this form of therapy. Intercurrent ovarian failure and abortion should be anticipated and prophylactic treatment instituted. 5. 5. The combined one-two employment of equine and chorionic gonadotropins has proved more effective than the use of cyclic equine gonadotropic therapy alone. 6. 6. Cyclic gonadotropic therapy in our hands fails to insure cyclic bleeding, thus indicating inadequate production of complete ovarian responses. 7. 7. Equine gonadotropic therapy is only one of the methods available for the treatment of ovarian failure.