Sonographic assessment of ovarian and endometrial changes during long-term Norplant use and their correlation with hormonal levels.

OBJECTIVE: To study the probability of ovulation and subclinical abortion during long-term use of Norplant and to assess the concomitant endometrial development. DESIGN: This was a prospective nonrandomized comparative study. The ovaries and endometrium were assessed daily by ultrasonography during 59 menstrual cycles in 50 women who were using Norplant for > 1 year. Serum concentrations of E2, P, FSH, LH, pregnancy specific beta 1 glycoprotein (Sp1), and hCG were also daily measured. The findings were compared with those in 35 ovulatory cycles in normal fertile women not using contraception. SETTING: Clients of the Family Planning Clinic of Assiut University Hospital (Norplant users) and the hospital women staff (controls). RESULTS: Sonographic and hormonal evidence of ovulation were observed in one third of Norplant users; two of them resulted in conception. However, the majority of these ovulatory cycles showed low midcycle peaks of E2, FSH, and LH and evidence of luteal phase defect (LPD). Excessive follicular enlargement was observed in 46% of the cycles. Norplant users had significantly thinner endometrium that did not exhibit the normal phasic changes in sonographic texture. Apart from conceptive cycles, no rise in Sp1 or hCG was observed. CONCLUSIONS: Norplant acts mainly by inhibiting ovulation, but when this occurs, it is associated with LPD and subnormal endometrial development. Subclinical abortion does not contribute to the contraceptive effect.

PIP: 59 cycles in 50 women with Norplant inserted 18-48 months previously were observed daily with ultrasonic scanning and analysis of serum estradiol, progesterone, FSH, LH, pregnancy-specific beta1 one-glycoprotein (Spl) and hCG, compared to 38 menstrual cycles in matched controls not using contraception. Subjects were all parous, married clients at the Family Planning Clinic of Assiut University Hospital, Assiut, Egypt, or hospital staff controls. 35 of the 38 control cycles were ovulatory, and 3 conceptions were noted by ultrasonic and hormonal criteria. In Norplant users there were waves of folliculogenesis, some even occurring during vaginal bleeding. Estradiol levels were highest when the largest follicles were seen in anovulatory cycles, and lowest in quiescent cycles with no follicle development. This correlation was highly significant (p0.01).

The recovery of fertility during breast-feeding in Assiut, Egypt.

A longitudinal study of twenty-six breast-feeding and twelve non-breast-feeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breast-feeding frequency on the period of lactational anovulation. Breast-feeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breast-feed. Ovulatory and non-ovulatory breast-feeders reported similar frequencies of breast-feeding episodes. The introduction of dietary supplements commonly preceded ovulation. An algorithm using three simple variables observable to the breast-feeding mother was found to predict up to 100% of the first ovulations. All breast-feeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breast-feeding.

PIP: A longitudinal study of 26 breastfeeding and 12 non-breastfeeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breastfeeding frequency on the period of lactational anovulation. The breastfeeding group consisted of women ages 18-40 who had successfully breastfed at least 1 child. Breastfeeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breastfeed. Ovulatory and non-ovulatory breastfeeders report similar frequencies of breastfeeding episodes (9-10 times in 24 hours). The introduction of dietary supplements commonly preceded ovulation. An algorithm using 3 simple variables observable to the breastfeeding mother was found to predict up to 100% of the 1st ovulations. All breastfeeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breastfeeding.

Effect of aspirin and indomethacin on the serum and urinary calcium, magnesium and phosphate.

Recent data have shown that administration of prostaglandin inhibitors to patients with hypercalciuric nephrolithiasis decreased urinary calcium excretion, implying a possible role for prostaglandins in calcium excretion. To explore this hypothesis, we investigated the effect of single dose or 7 days' administrations of aspirin (100 mg/kg orally) or indomethacin (20 mg/kg, orally) on the urinary and serum concentrations of calcium, magnesium and inorganic phosphate. Experiments were performed in normocalcaemic and hypercalcaemic rats. Hypercalcaemia and hypercalciuria were induced in male Wistar albino rats by administration of vitamin D3 (20,000 IU/daily) for 7 days. Aspirin and indomethacin both significantly lowered the urinary calcium excretion in normocalciuric and hypercalciuric rats. The acute administration of indomethacin caused greater reduction of calcium excretion than that produced by the acute administration of aspirin, whereas aspirin showed greater activity than indomethacin after the long-term use of each. Aspirin induced hypocalcaemia in normocalcaemic rats and abolished the hypercalcaemia in hypercalcaemic rats. On the contrary, indomethacin, a specific prostaglandin biosynthesis inhibitor, increased serum levels of calcium. Hypophosphataemia was observed only after the administration of a single dose of aspirin in normocalcaemic rats, while the reduction of urinary phosphate excretion was investigated in hypercalciuric rats after the acute and chronic administration of indomethacin. Serum levels of phosphate were not altered significantly by acute or chronic administration of indomethacin. A single dose of indomethacin significantly reduced urinary excretion of magnesium in both groups of rats. However, the acute and chronic administration of aspirin resulted in non-significant changes in serum and urinary concentrations of magnesium. These data suggest that aspirin has hypocalcaemic and hypocalciuric actions while indomethacin has only a hypocalciuric effect. Aspirin may produce these actions by two mechanisms, one of them like that of indomethacin which is dependent on the inhibition of biosynthesis of prostaglandins, and another possible mechanism that is not related to the inhibition of prostaglandin biosynthesis. This suggestion may be supported by the discrepancy between the effects of aspirin and indomethacin on the renal handling and serum concentrations of magnesium and inorganic phosphate.

The recovery of ovarian function during breast-feeding.

The pattern of breast-feeding was daily recorded and the serum concentrations of prolactin (PRL), FSH, LH, estradiol (E2) and progesterone (prog) were measured at weekly intervals in 26 breast-feeding mothers from the time of delivery and up to the resumption of regular ovulation or to the end of the first postpartum year. Twelve postpartum non-breast-feeding women were similarly studied as controls. An algorithm was used to characterize ovulatory events into three types: the first, with evidence highly suggestive of normal ovulation (EHSO), the second, with evidence of probable ovulation (EPO) and the third with evidence indicating questionable ovulation or deficient corpus luteum function (QO/DCT). Pregnancy preceded the first menstruation in one woman in each of the breast-feeding and control groups. Of the 19 breast-feeding women who started to menstruate during the first postpartum year, five had EHSO, one had EPO, 5 had EQO/DCL and 7 had anovulatory (AO) menstruation. The corresponding figures in the 11 controls were 6, 2, 3 and 0. Pregnancy occurred before a second menstruation in one woman in both the study group and the controls. In 18 breast-feeding women observed, the second menstruation was preceded by EHSO in 7, by EPO in 3, by EQO/DCL in one and AO in 7. In 10 controls the corresponding figures were 7, 3, 0 and 0. Out of a total of 79 menstruations observed during breast-feeding the incidence of AO was 30% and of QO/DCL was 15%. In actively breast-feeding mothers, hyperprolactinemia persisted for more than 1 yr. However, menstruation and ovulation occasionally occurred before the drop of PRL to concentrations seen during the normal menstrual cycle. In the majority of women, low E2 levels were present during lactational amenorrhea, but with occasional spikes in some. A few women maintained somewhat high values of E2 for several weeks before the resumption of menstruation. The implications of these hormonal findings to the attempts to improve on the contraceptive effect of breast-feeding are discussed.

Hormonal changes during the first year of use of subdermal levonoregestrel implants, Norplant.

Sixty-three women had NORPLANT implants inserted during the first eight days of the menstrual cycle. Blood specimens were withdrawn at the time of insertion and every three days during one of the following months of observation; the first, third, sixth, ninth and twelfth month after insertion. Ten subjects were sampled at multiple times during implant use. A total of 83 months of observation was available. The serum concentrations of levonorgestrel (LNG), FSH, LH, prolactin (PRL), estradiol (E2) and progesterone (prog) were measured in each specimen. LNG concentration rapidly declined during the first 15 days of use, the decline became more gradual during the subsequent two weeks, and an almost steady level was reached during the remainder of the year. There were no significant trends of change in the levels of FSH, LH, E2 and prog during the year. Frequent peaks in E2 concentration were observed and were generally associated with or followed by LH surges. PRL concentration showed a slight but significant rise during the second half of the year. Rises in prog concentration suggestive of ovulation occurred in 36 percent of the months of observation. However, in all these instances, there were evidences suggestive of deficient luteal phase. The bleeding episodes were usually, but not always, related to decline in E2 and prog concentrations.

Effect of oral contraception on serum bile acid.

Eighteen normal women, 20 with active urinary schistosomiasis, and 25 with past histories of viral hepatitis were given a contraceptive pill containing 0.05 mg ethinyl estradiol and 0.5 mg levonorgestrel for six consecutive cycles. Serum bile acid levels were measured by enzyme immunoassay method before and after 3 and 6 months of use. Simultaneously, conventional liver function tests (serum bilirubin, transaminases, alkaline phosphatase and albumin) were done. Serum bile acid concentration was not significantly changed by the contraceptive use in any group. The concentration of cholylglycine (the main bile acid measured) did not correlate with the values of any of the other tests. Pretreatment values of serum cholylglycine were significantly lower in the past-hepatitis group. The difference was maintained during treatment.

PIP: 18 normal women, 20 with active schistosomiasis, and 25 with past histories of viral hepatitis were given a contraceptive pill containing 0.05 mg ethinyl estradiol and 0.5 mg levonorgestrel for 6 consecutive cycles. Serum bile acids were measured by enzyme immunoassay method before and after 3 and 6 months of use. Simultaneously, conventional liver function tests (serum bilirubin, transaminases, alkaline phosphatase, and albumin) were done. Serum bile acid concentration was not significantly changed by contraceptive use in any group. The concentration of cholylglycine (the main bile acid measured) did not correlate with the values of any of the other tests. Pretreatment values of serum cholylglycine were significantly lower in the past-hepatitis group. The difference was maintained during treatment.

Prognostic value of biochemical tests in the assessment of fetal outcome in threatened abortion.

Maternal concentrations of serum progesterone, oestradiol, chorionic gonadotrophin, Schwangerschaftsprotein 1 and placental protein 5 were measured in 67 patients with threatened abortion. The levels of all biochemical variables were significantly reduced in those patients who had an unfavourable outcome. The clinical efficiency of each of these tests was very similar.

Circulating levels of placental proteins, placental protein 5 (PP5), placental lactogen and Schwangerschafts-protein 1 (SP1), in antepartum eclampsia.

Placental protein 5 (PP5), Schwangerschaftsprotein 1 (SP1) and human placental lactogen (hPL) were measured in 36 serum samples from seven women with antepartum eclampsia. PP5 levels were generally elevated, hPL levels were reduced and SP1 levels were within the usual ranges.

Effects of oral contraception on liver function tests and serum proteins in women with past viral hepatitis.

Forty-three women who had viral hepatitis one or more years ago and 35 healthy women who were age and parity matched were given an oral contraceptive containing 0.05mg ethinyl estradiol and 0.5mg levonorgestrel for six consecutive months. Liver function tests (serum bilirubin, SGOT, SGPT and serum alkaline phosphatase) and serum proteins (total, albumin, globulins, ceruloplasmin, haptoglobin and alpha-1 antitrypsin) were measured before beginning treatment and after three and six months of use. Past hepatitis women experienced increased unconjugated bilirubin, SGOT, SGPT and alkaline phosphatase levels throughout the six months while the control women showed less pronounced changes during the first three months with tendency to reversion to normal during the subsequent three months; the group X time of test interactions were significantly different between the two groups. Serum haptoglobin decreased significantly in both groups but the past-hepatitis group showed a more persistent change with time. Changes also occurred in serum albumin, alpha-1 and beta globulins, ceruloplasmin but without group effect or group X time interactions.

Effects of oral contraception on liver function tests and serum proteins in women with active schistosomiasis.

Thirty-eight women with urinary or intestinal schistosomiasis but without clinical or laboratory evidence of hepatic involvement and 30 healthy control women were treated with an oral contraceptive containing 0.05mg ethinyl estradiol and 0.05mg levonorgestrel for six consecutive months. Liver function tests (serum bilirubin, SGOT, SGPT, serum alkaline phosphatase) and serum proteins (total, albumin, globulins, ceruloplasmin, haptoglobin and alpha-1 antitrypsin) were measured before beginning the treatment and after three and six months of use. Both group experienced significant increases in SGOT, SGPT and serum alkaline phosphatase during the first three months of treatment with tendencies to decrease during the subsequent 3 months. No change occurred in serum bilirubin. There was significant decreases in serum albumin and haptoglobin and increases in alpha-1 globulin, ceruloplasmin and alpha-1 globulin, there were no significant differences between schistosomiasis patients and the controls in terms of changes in any laboratory test as a result of the treatment, thus suggesting that patients with active schistosomiasis do not incur a higher risk of hepatic dysfunction while using oral contraception.

Sex steroids in women with liver cirrhosis.

Eighteen women with hepatic cirrhosis were examined for plasma levels of testosterone, estrone, estradiol, progesterone and sex hormone binding globulin. For eight who were amenorrheic, with advanced liver cirrhosis and ascites, the reduction of testosterone and rise in estrone and sex hormone binding globulin concentrations were significant. Plasma extradiol and progesterone were lower than normal levels, but the differences were not statistically significant. The other ten patients were menstruating (mostly irregularly), and their hormonal levels were assessed in different states of their cycles. All of them did not ovulate, had low levels of plasma progesterone and also showed consistent estrone concentration excess relative to estradiol and significant lowering of testosterone and elevation of sex hormone binding globulin. These findings are compared with previous reports on males with liver cirrhosis.