Prevalence of premature ovarian failure in patients with systemic lupus erythematosus.

OBJECTIVE: To estimate the prevalence of premature ovarian failure (POF) and its associated factors in patients with systemic lupus erythematosus (SLE). METHODS: Cross-sectional study including consecutive SLE women <60 years of age attending a rheumatology clinic. A face-to-face interview was undertaken to obtain demographic, gynaecological and lupus characteristics. Additional rheumatologic and endocrine data were retrieved from patients' medical records. POF prevalence was estimated in the study sample and in a subgroup of patients aged <40 years at interview. Associations between POF and selected variables were assessed by logistic regression analyses. RESULTS: A total of 961 patients were analysed. Prevalence of POF, secondary amenorrhea of known cause, menopause and hysterectomy were 5.4%, 0.8%, 7.8% and 4.4%, respectively. In 674 (70%) patients who had not been exposed to cyclophosphamide (CYC) the prevalence of POF was 0.6%. Disease activity over time (OR 1.4 (CI 95% 1.0-1.8, p < 0.05)) and CYC treatment (OR 5.9 (CI 95% 1.8-18.8, p < 0.01)) were associated with higher prevalence. Association between POF and endocrine autoimmune diseases was not found. CONCLUSIONS: In the absence of CYC treatment, the prevalence of POF in lupus patients is consistent with that reported in the general population. The existence of autoimmune processes at the ovary seems unlikely in most lupus patients.

Disease activity during the premenopausal and postmenopausal periods in women with systemic lupus erythematosus.

PURPOSE: Cyclophosphamide-induced ovarian failure has been reported to be protective against flares of systemic lupus erythematosus (SLE). We studied whether patients with SLE experience a decrease in disease activity after natural menopause. SUBJECTS AND METHODS: We studied 30 SLE patients with natural menopause who had been observed at least 2 years before and after menopause and who did not receive hormone replacement therapy or danazol. Menopause was defined as the date of the last self-reported menstrual period. Disease activity was assessed retrospectively by medical chart review using standard measures (the SLE disease activity index) during the immediate premenopausal and postmenopausal periods, and 2 (n = 30 patients), 3 (n = 19), and 4 (n = 13) years before and after menopause. We also compared the use of health services and medications. RESULTS: Patients were studied for a mean (+/- SD) of 6.4 +/- 1.7 years (premenopausal, 3.3 +/- 0.9 years; postmenopausal, 3.2 +/- 0.9 years). During the premenopausal periods, the mean disease activity score was 2.3 +/- 2.3 (range, 0 to 9 on a 0 to 105 scale), compared with 2.3 +/- 2.9 (range, 0 to 12; P = 0.37) after menopause. The maximum disease activity score was somewhat greater in the premenopausal period (7.9 +/- 6.0 [range, 0 to 22] vs. 5.8 +/- 5.1 [range, 0 to 22]; P = 0.04). The incidence rates of flares (0.56 per year vs. 0.43 per year, P = 0.20) and severe flares (0.17 per year vs. 0.12 per year, P = 0.33) were similar in the premenopausal and postmenopausal periods. Differences in disease activity scores (mean and maximum) and the number of visits to a rheumatologist's office were only significant when the fourth year before menopause was compared with the fourth year after menopause. CONCLUSIONS: Disease activity is mild during the premenopausal and postmenopausal periods in women with SLE. A modest decrease, especially in the maximum disease activity, is seen after natural menopause.

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.

Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic ovary syndrome.

BACKGROUND: The present study was carried out to investigate the functional significance of the reduced dopaminergic tone in subjects affected with polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls (six lean and five obese). In addition, circulating PRL bioactivity was evaluated by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral administration of metoclopramide resulted in a significant increase in serum PRL in all subjects; however, the highest increments, regardless of body mass index (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when compared with all other groups. CONCLUSIONS: These data support the existence of low DA hypothalamic tone in PCOS women that is likely involved in the inappropriate LH and PRL secretion frequently seen in this syndrome. In addition, our results suggest changes in PRL bioactivity in obese PCOS that may play a role in the development of hyperinsulinemia; however, whether PRL has a functional significance in the development of the metabolic disturbances frequently seen in PCOS remains to be elucidated.

Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health.

OBJECTIVE: To evaluate relationships between bone mineral density and use of steroid hormonal contraceptives. METHODS: This was a multicenter cross-sectional study in seven centers in three regions of the developing world from April 1994 to June 1997. Women 30-34 years old attending family planning clinics, with at least 24 months of lifetime use of combined oral contraceptives (OC), depot-medroxyprogesterone acetate (DMPA), or levonorgestrel implants, or no or only short-term (less than 6 months) use of steroid hormonal contraceptives, had bone mineral density (BMD) measured at the distal radius and the midshaft of the ulna using single-photon x-ray absorptiometry. RESULTS: In the study, 2474 women were examined. For OC use, adjusted mean BMD was significantly higher in short-term, current users compared with women who never used hormonal contraceptives. For DMPA and levonorgestrel implants, adjusted mean BMD was statistically significantly lower in short-term current users compared with those who never used hormonal contraceptives. For all three hormonal methods, there were no significant differences in BMD between past users of hormonal contraceptives and never users, even among those who had used the methods for 4 or more years. The magnitude of changes in BMD was small and less than one standard deviation (SD) from the mean of those who never used steroid contraceptives. CONCLUSION: This study suggests that hormonal contraceptive use by young adult women is associated with small changes in BMD that occur early after initiation of use and are reversible.

Prolactin size variants during pregnancy in women with ovulatory hyperprolactinemia: characterization by isoelectric focusing and lectin affinity chromatography.

Previous studies from this laboratory have demonstrated the occurrence of important changes in PRL size heterogeneity in women with ovulatory hyperprolactinemia during gestation. A similar observation has been made, in normal women, for glycosylated PRL, which shows a progressive decrease as pregnancy progresses. In this study we decided to investigate the contribution of G-PRL on PRL heterogeneity throughout gestation in women with ovulatory hyperprolactinemia. Serum samples obtained throughout gestation were analysed by SDS-PAGE followed by immunoblotting and by isoelectric focusing of gels as well. The results indicated that, independent of the stage of pregnancy, the relative amounts of G-PRL as compared with the nonglycosylated form of the hormone remained quite constant. In addition, isoelectric focusing analyses of serum samples consistently resulted in an identical isoelectric point of PRL throughout all of the gestational period. These results suggested that changes in the relative proportions of PRL size species during pregnancy were not correlated with the degree of PRL glycosylation. Moreover, these observations further extended and supported the concept that the occurrence of PRL size heterogeneity depends mainly on thiol-disulfide interchange mechanisms, among PRL molecules, at the pituitary level.

[Prolactin variants in serum and amniotic fluid of women with ovulatory hyperprolactinemia]. / Variantes de prolactina en suero y líquido amniótico de mujeres con hiperprolactinemia ovulatoria.

There is enough evidence that prolactin (PRL), like many other pituitary hormones, is composed by multiple forms that differ from each other by size charge. Although they can be seen in the pituitary glands of a variety of species, their biological significance, identity and chemical nature still remain poorly understood. Recently, a new syndrome characterized by normal ovarian function in the presence of sustained hyperprolactinemia has been reported by our group. In these women, highly abnormal percentages of serum big big PRL have been consistently demonstrated. This observation suggests that big big PRL is immunologically similar, but biologically less active than monomeric or little PRL. In this study we have determined then molecular size heterogeneity of immunoreactive PRL in serum and amniotic fluid from two ovulatory hyperprolactinemic subjects (subjects A and B) who had, under non-pregnant conditions, large amounts of serum big big PRL, throughout different stages of parturition. Control subjects consisted of two women at the end of pregnancy in whom PRL species demonstrated a normal size distribution (subjects C and D). Mean basal levels of PRL were the highest in subjects A and B and remained constant during labor. In the control subjects a remarkable decline in PRL levels was observed during the periparturitional period. This pattern of PRL release was not correlated with changes in steroid hormone concentrations. The relative proportions of PRL size variants throughout delivery showed no apparent changes in all four subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function.

We have demonstrated the selective secretion of high mol wt PRL series (big big PRL) in women with hyperprolactinemia and normal ovarian function. This observation suggests that big big PRL is immunologically similar, but biologically less active, than monomeric or little PRL. In this study we determined the molecular size heterogeneity of immunoreactive PRL in the serum from two ovulatory hyperprolactinemic women (subjects A and B) who had large amounts of serum big big PRL during a menstrual cycle and/or gestation. Serum samples obtained throughout the menstrual cycle (days 6, 10, 14, 17, 23, and 28, taking as day 1 the first day of bleeding) and pregnancy (weeks 7, 9, 11, 15, 20, 25, 30, 34, and 38) were fractionated by gel filtration chromatography. PRL was identified in column eluates by specific RIA. Two additional pregnant women, one with a bromocriptine-treated PRL-secreting adenoma (subject C), and a normal woman (subject D) were studied. Big big PRL was the predominant species throughout the different phases of the menstrual cycle in subject B, comprising 70-80% of the total immunoreactive PRL. Most of the remainder was big PRL, and little PRL was present in only small amounts (6-12%) during the luteal phase. During their pregnancies, the serum PRL in subjects A and B initially was mostly big big PRL, but later in gestation the PRL composition shifted from the high mol wt variants to little PRL. The infant's cord (subject A) and peripheral (subject B) serum at birth contained appreciable quantities of big big and big PRL, respectively. These results indicate that structural changes in PRL occur during pregnancy and the menstrual cycle which are probably influenced by the hormonal environment. In addition, the occurrence of larger mol wt PRL species in the serum of the infant of a hyperprolactinemic mother suggests that the presence of high proportions of big big PRL in the serum is genetically determined.

Familial occurrence of big-big prolactin as the predominant immunoreactive human prolactin species in blood.

The occurrence of big-big prolactin (PRL) as the major form of circulating immunoactive PRL has been described in ovulatory hyperprolactinemia. In this study, we have analyzed the heterogeneity of circulating human PRL in 17 members of three families in which one member, bearing galactorrhea-hyperprolactinemic syndrome, was known to have serum big-big PRL as the predominant circulating species. Gel filtration patterns of serum samples of all subjects revealed the presence of significant proportions of big-big PRL in more than one member of the same family, thus suggesting the familial occurrence of big-big as the predominant immunoreactive PRL species in blood.

Return to ovulation following the use of long-acting injectable contraceptives: a comparative study.

A comparative study was undertaken in twenty-four Mexican women who discontinued the use of depo-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) to assess the time required for the return to menses and ovulation. All subjects were exposed to long-acting injectable contraceptives for at least one year, and were followed prospectively. Serum progesterone levels were determined weekly in all subjects beginning 3 months after the last progestogen injection. Mean time to return to ovulation occurred significantly earlier (p less than 0.001) after NET-EN (2.6 months) as compared with DMPA (5.5 months). No correlation between the return to ovarian function and the duration of steroid exposure was found. The overall data was interpreted as demonstrating a clear-cut difference between the two long-acting progestogens in terms of ovulation suppression.

Ovarian function following a single administration of depo-medroxyprogesterone acetate (DMPA) at different doses.

The effects of a single administration of depo-medroxyprogesterone acetate (DMPA) at different doses upon ovarian function was studied in a group of healthy ovulating Mexican women. Single doses of DMPA of 25, 50, 100, and 150 mg were intramuscularly administered. Ovarian function was assessed by the measurement of the serum levels of 17 beta-estradiol and progesterone in blood samples drawn twice weekly for 6 months after DMPA administration. The results disclosed that ovulation was inhibited in all cases for at least 3 months following DMPA administration even at the lowest dose, whereas the return of luteal function exhibited a significant positive correlation with the dose of DMPA administered. As expected, follicular activity preceded that of luteal function in all subjects. A correspondence between serum medroxyprogesterone concentrations and ovarian function was found. The overall data indicated that the currently used contraceptive formulation (150 mg) is well above the effective pharmacologic range, and suggested that the dose can be substantially reduced without losing its anovulatory potency.