Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

PIP: The study sought to examine the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. This observational, prospective, case-controlled, comparative study occurred at the Family Planning Clinic of PROFAMILIA in Santo Domingo, Dominican Republic. 31 subjects agreed to receive Norplant contraceptive implants between 13-77 months prior to this study and there were 12 nonhormonal contraceptors who also volunteered to participate. Follicle stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for 1 menstrual cycle, and almost 1/2 of the cycles of norplant acceptors were anovulatory: the remainder (55%) had some form of dysfunction such as diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from controls. Anovulation is clearly 1 of the main mechanisms of Norplant action, but even in presumptive ovulatory cycles, the dysfunctions described could have contributed to the high contraceptive effectiveness of Norplant.

The place of progesterone in human contraception.

Progesterone, the natural hormone produced by the corpus luteum and other steroid-secreting glands, is endowed with antiestrogenic action and has a fundamental role in the initiation and maintenance of pregnancy and in the regulation of gonadotropin secretion. Although it was discovered half a century ago, it has found little clinical use as a therapeutic agent due to its low potency and extensive degradation following oral administration in comparison with a variety of highly potent synthetic analogs that became available in the last three decades. When delivered systemically, a large proportion of the dose bypasses degradation in the gut and liver, and progesterone can achieve effective levels in target tissues for clinical use. Sustained administration via compressed pellets implanted subdermally or silicone rubber rings placed in the vagina produced circulating levels of progesterone within the lower third of those found in the luteal phase of the human menstrual cycle. Those levels were shown to delay the recovery of fertility in nursing women without adverse effects to the mother or the infant. Progesterone transferred to the babies via the breast milk did not change their rate of pregnandiol-3-alpha glucuronide excretion. It is concluded that sustained administration of the natural hormone progesterone may be an effective and safe contraceptive method for nursing women.

Defective luteal phase--measurement and evaluation of the ovarian hormone before and during cyclofenil (bis-P-acetoxphenyl) cyclo-hexylidenemethane (Compound 6066) treatment.

PIP: The nature of defective luteal phase (DLP) was investigated by the measurement and evaluation of the ovarian hormone before and during Cyclofenil (bis-p-acetoxphenyl) cyclo-hexylidenemethane treatment. Total urinary estrogens and plasma progesterone were measured in 50 infertile patients with DLP. Prior to treatment these patients revealed wide variations in their urinary estrogen pattern while plasma progesterone was uniformly low. Treatment results were dependent on the dose of Cyclofenil and on the baseline estrogen configuration of the patient. The pregnancy rate was 28%. The results indicated that follicular dysmaturity precedes luteal insufficiency in the majority of cases. Therefore, treatment should be aimed at correcting the hormonal imbalance both at hypothalamico pituitary axis level and at the ovarian level rather than simple substitution therapy. Both of these qualities are present in Cyclofenil.^ieng

[Participation of 17 alpha-hydroxyprogesterone in the mechanism of ovulation]. / Participación de la 17 alfa-hidroxiprogesterona en el mecanismo de la ovulación.

PIP: Progesterone (P) and 17 alpha-hydroxyprogesterone (17 OH-P) were analyzed daily during the menstrual cycle in women with both ovulatory and anovulatory cycles, without any other endocrine alteration. The plasma levels of 17 OH-P in 65 samples obtained during the follicular phase of the ovulatory cycles were 1.057 ng/ml, consistently higher than the P levels, which were .492 ng/ml, with a 17 OH-P/P ratio of 2.16. On the other hand, the plasma levels of 17 OH-P obtained during the same phase of the anovulatory cycles were .288 ng/ml. The difference between ovulatory and anovulatory cycles was statistically significant (p less than .001). The P levels were .156 ng/ml and the 17 OH-P/P ratio was 2.76. In the 2nd part of the ovulatory cycles, the 17 OH-P/P ratio was .46, and in the same part of the anovulatory cycles the ratio was 2.39. The total values of both steroids and the individual values of 17 OH-P differed between the 2 types of cycles (p less than .001). The findings show that 17 OH-P is an indicator of follicular development and that it could be used to predict the occurrence of ovulation.^ieng

[Tissue distribution of progesterone-7-H3 in the female genital tract 8 hours after intravenous administration]. / Depósito tisular de progesterona-7-H3 en el aparato reproductor femenino, ocho horas después de su administración endovenosa.

PIP: 6 patients, ages 32-55 years, were selected to establish radioactive progesterone distribution in the genital tract, and deposition in skin and fat tissue. 1/2 of the patients were in the menstrual proliferative phase, and the rest were in the secretory phase. 250 uci of progesterone-7-h cubed was given intravenously to all patients, and total hysterectomy and salpingo-oophorectomy were performed 8 hours later. A piece of skin was taken as well as some fat tissue from the anterior abdominal wall. The tissues studied were skin, fat tissue, ovary, tube, and uterus. The uterus was sectioned into 3 parts (superior, median, inferior) and the cervix was sectioned into 2 (endocervix and ectocervix). In all the patients, urine was collected during 3 consecutive days and at the time of operation; 10 ml was taken then and at the 5th postoperative day. The largest concentration of radioactive material was found in the proliferative phase patients (in fat tissue); in the secretory phase it was concentrated in the skin, uterus, and myomas. Excretion of radioactive material was 32.5% in the urine, blood radioactivity at the time of operation was 2.62%, and 0.33% of the administered total dose at the 5th postoperative day. In a previous similar study with chlormadinone acetate, urinary excretion was 17.5% and the largest radioactive material concentration occurred in fat tissue, regardless of the day of the cycle. These results may show that natural and synthetic hormones have different action mechanisms at their genital effectors, and different fat tissue deposition. (author's)^ieng