Ramón Aznar

Low Doses of Progestogen as an Approach to Fertility Control

A clinical program was undertaken to establish the contraceptive effectiveness of minimal hormonal supplementation with chloramadinone acetate .5 mg given daily in both a cyclic and continuous pattern. Nonlactating women of proven fertility 36 years and under were given the drug daily as a contraceptive. They were all involved in an intensive study of the reproductive system. With the cyclic use of .5 mg chlormadinone acetate there were 2 pregnancies on of which was due to failure of the patient to continue the regimen. The principal side effect was intramenstrual bleeding and spotting in about 20-25% studied. Endometrial biopsies showed that the drug did not prevent the development of a normal secretory endometrium this was seen in 80 of the 109 specimens. Of 122 urinary pregnanediol determinations done 33(27%) had concentrations at ovulatory levels. In culdoscopic findings follicular activity or corpora lute were found in 18 of 19 patients studied. Contraceptive protection was also afforded with continuous administration of the drug. With continuous administration of the drug approximately 60% of the women had cycles of 24-34 days the longer cycle being more common and 80-90% had 7 or less days of bleeding per month. The endometrium showed less evidence of normal secretory activity than that seen with cyclic administration of the same drug. Preliminary studies of ovarian biopsy specimens suggest that ovulation occurs as in cyclic treatment.

Intrauterine contraception with the progesterone-T device

Abstract The possible mechanism of action of the progesterone-releasing intrauterine device has been studied by means of determination of the action that uterine washings have on the metabolism and capacitation of human and rabbit spermatozoa. Uterine washings from normal, untreated women, induce, in human spermatozoa, the same changes although of lesser magnitude, that have been previously reported as possibly participating in the uterine stage of capacitation. Uterine washings obtained from progesterone-T wearing women produce a significant decrease in oxygen uptake and glucose utilization, an inhibition of the BANA-hydrolytic activity, and changes in the tetracycline binding and release processes. All these changes support the hypothesis that at least part of the mechanism of action of the progesterone-releasing type of intrauterine devices is due to a direct capacitation inhibiting effect of the uterine secretion. This hypothesis is strengthened by the direct demonstration of inhibition of in vitro rabbit spermatozoa capacitation produced by these washings.

Intrauterine devices and menstrual blood loss a comparative study of eight devices during the first six months of use

An experiment was conducted to determine changes in menstrual blood loss caused by IUDs. 78 volunteer women of similar age and parity were randomly selected from among those requesting IUDs from the outpatient department of the National Medical Center of the Mexican Institute of Social Security. Menstrual blood loss and hemoglobin were measured for 1-2 control cycles and for 6 postinsertion cycles. Of the 8 different types of IUDs used, the Lippes Loop and the copper-releasing devices caused a statistically significant increase in blood loss and a related decrease in hemoglobin. The steroid-releasing devices caused no significant increase in blood loss and no significant changes in hemoglobin concentration. The rigid copper devices caused the greatest increase in blood loss. The noted changes were clearly established by the 3rd postinsertion cycle.

Subcellular distribution of trace metals in the normal and in the copper treated human secretory endometrium.

Abstract The subcellular distribution of some metals has been studied in the normal human secretory endometrium and in the secretory endometrium of women wearing a copper-T intrauterine device. The sustained release of copper inside the uterine cavity induces some significant changes in the metal composition of this tissue; Mg, Ca and Cu increase while Zn decreases. Neither Na nor K concentrations show any significant change. Under these conditions, endometrial nuclei concentrations seem to be able to passively come to equilibrium with the tissue concentrations of the elements studied, showing only a significant retention of Ca. On the contrary, mitochondria show differential concentrations of all metals. Ca is retained, but all the other elements remain at low levels. Copper is significantly increased in all fractions, but the relative increase is particularly noticeable in the microsomes (6 x). Zinc tends to decrease in all fractions but reaches statistical significance only in the microsomes and the supernatant. These results are analyzed in relation to the mechanism of action of the Cu-T.

EEG abnormalities found in healthy women under contraceptive medication. II. Long term studies.

In a previous study EEG abnormalities were detected in 2 of 24 healthy women during the 1st 3 months of treatment with various ovulatory and anovulatory contraceptive regimens. The present study is a follow up of the same group of women to detect possible EEG abnormalities occurring at the 6th and 12th months of treatment and those occurring within the 1st month after discontinuation of contraception. Only 17 women were studied (the 7 others were excluded due to voluntary treatment termination and pregnancy); they were divided into groups: 1) coil (5 cases) 2) microdoses (5 cases) and 3) sequential (4 cases) and combined (3 cases). In each case 3 consecutive pairs of routine EEG recordings (during the 6th and 12th months of contraceptive treatment and within 1st month of contraceptive discontinuation) and an equal number of plasma samples for progesterone/17 beta estradiol determination were taken. EEG routine recordings were also practiced during menstruation and during sleep. Procedures for routine EEG recordings and interpretation hormone determination standardization of dates and statistical significance of changes along the menstrual cycle were done as in the previous study. 4 of 7 patients in group 3 (the anovulatory sequential and combined contraceptive regimen) exhibited subclinical pseudoparoxysmal EEG discharges at the 6th and 12th months of treatment. These abnormalities may be due to the effect of specific hormone content of these particular compounds as they were not seen in control records taken before and after treatment and were seen on dates corresponding to the secretory phase of ovulatory cycles and concomitant to hormonal changes reflecting ovarian inhibition. In the coil group no abnormal EEG signs were observed in patients before during and after the regimen. 1 patient in the microdose group was found to have EEG abnormalities but the abnormalities were not attributed to the hormone content of the compound as abnormal EEG signs were found before and after treatment and were not concomitant to ovarian inhibition. No EEG abnormalities were observed in records taken during menstruation and during sleep of all the subjects.

The effect of various contraceptive hormonal therapies in women with normal and diabetic oral glucose tolerance test

The effect of various contraceptive hormonal therapies was studied in 176 women with normal and diabetic oral glucose tolerance tests (OGTTs). 160 women showed normal and 16 showed diabetic patterns on the 14th day of a control cycle, during the 3rd and 6th months of contraceptive therapy, and 3 months after having stopped medication. The women were divided into groups and fitted with a Lippes loop, treated with low doses of chlormadinone acetate, lynestrenol, and megestrol acetate or with a sequential estrogen-progestogen contraceptive containing either ethinyl estradiol or mestranol. The only groups showing modifications of OGTTs were the sequential estrogen-progestogen groups, where the OGTT curves of the normal groups became abnormal while those of the diabetic group improved. The modifications disappeared 3 months after discontinuation of the medication which can be interpreted as a direct effect of the steroids on carbohydrate metabolism.

Cyclic changes in salivary activity of N-acetyl-beta-D-glucosaminidase. A possible efficient indicator for predicting ovulation and pregnancy.

Salivary activity of N-acetyl-beta-D-glucosaminidase showed a characteristic pattern of changes during the normal menstrual cycle with a distinct peak on Day 13, 14, or 15 before the next menstruation. This peak of enzyme activity occurred withing one day of the nadir of basal body temperature and was absent in women with spontaneous or iatrogenic anovulatory cycles. These results are stongly suggestive that the salivary determination of this activity may be convenient indicatior for determining the day of ovulation.

Effect of intrauterine copper on the nucleic acids, polysome pattern, and glycoprotein composition of the human endometrium

The modifications induced by the intrauterine release of copper in the macromolecular and glycoprotein composition of the proliferative and secretory human endometrium were studied. In addition, the endometrial changes produced in women users of copper-T intrauterine devices in the polysome pattern and in the content of ribonucleoprotein particles were determined during the secretory phase. A group of ten untreated normal women (control group) and 15 users of 200 mm.-2 copper-T intrauterine device were selected for this study from the outpatient clinic of the Hospital de Ginecologia y Obstetricia No. 2 del Instituto Mexicano del Seguro Social. The main changes observed in the copper-T users were: a significant decrease in the endometrial content of RNA in both phases of the menstrual cycle, a significant decrease in protein in the secretory phase, and drastic changes in the fucose-sialic acid ratios, which decreased during the proliferative and increased during the secretory phases. Normal human secretory endometrium contained 4.89 plus os minus 0.28 (mean plus or minus standard error (S. E.) mg. ribonucleoprotein particle per gram wet weight, while the endometrium of the Cu-T users showed a significant decrease to 2.52 plus or minus 0.17 (mean plus or minus S. E.). In addition, the Cu-T induced a decrease in the heavy components of the polysome pattern with a concomitant increase in the lighter components.

Effect of the intrauterine contraceptive device upon the biochemical composition of human endometrium

Abstract Biochemical composition of human endometrium was studied during the secretory and proliferative phases of 14 untreated normal young women and of 23 users of a large Lippes loop placed between 2 and 65 months previously. In the non-intrauterine contraceptive device (IUD) users, protein and potassium contents of the endometrium were higher and the sodium concentration and the fucose/sialic acid ratio were lower during the luteal than the proliferative phase. The main changes produced by the IUD were a significant decrease of ribonucleic acid (RNA) and sodium, and a 5 times increase in calcium during the proliferative phase and an increase of calcium, sodium, and fucose and in the fucose/sialic acid ratio in the secretroy phase. Secretory phase endometrium of IUD users has amounts of RNA, protein, and potassium lower than those of the control group. The observed changes are discussed in relation to the mechanism of action of the IUD.

Electrocardiographic Changes Induced by Insertion of an Intrauterine Device and Other Uterine Manipulations

A prospective study was carried out in normal women in order to investigate the effects of the following procedures on the electrocardiogram and blood pressure: (1) insertion of an intrauterine device (IUD)--the Lippes loop, Tcu-200, uterine progesterone system or Cu-7; (2) endometrial biopsy; and (3) uterine flushing. In groups in which a large IUD like the Lippes loop and/or a stiff IUD like the Cu-7 was inserted, the frequency of bradycardia was significantly higher than in any other groups. The severity of the bradycardia was similar in all of the groups and the frequency of this alteration was also similar among the nulliparous women or in those who complained of pain during the instrumentation, irrespective of the type of IUD inserted or the procedure carried out. No alarming modifications of blood pressure were observed and maintaining the patients in the recumbent position was sufficient to alleviate symptoms. In severe cases use of the Trendelenburg position should be enough to correct any alterations.