Impaired fat deposition in pregnancy: an indicator for nutritional intervention.

Unselective dietary supplementation of pregnant mothers can have adverse effects. It is essential to predict which mothers are nutritionally at risk and would benefit from supplementation. Preliminary studies indicated that mothers who increased their triceps skinfold by less than or equal to 20 micron during the second trimester were nutritionally at risk of having a small baby. In this study anthropometric indicators were explored in 81 Asian mothers living in Birmingham. Single (distance) measurements (eg, weight at 28 wk, etc) were not effective predictors. Changes in measurements of the arm during the second trimester were predictive, and triceps skinfold remained the most effective predictor of poor fetal growth. This measurement probably reflects the balance of energy intake minus energy expenditure during the critical second trimester when the mother would normally be laying down extra fat in anticipation of later fetal demands.

Plasminogen activators t-PA, u-PA and its inhibitor (PAI) in normal males and females.

We determined the plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity and their antigen levels including urokinase plasminogen activator (u-PA) in 33 male and 27 female normal subjects. Males had mean t-PA activity of 0.50 iu/ml which was significantly lower (p less than 0.01) than the females 0.64 iu/ml. Males had higher (p less than 0.001) mean PAI activity (15.5 AU/ml) as compared to females 10.3 AU/ml. The respective mean levels of t-PA and PAI antigen were significantly higher (p less than 0.01) in males (8.1 ng/ml and 17.6 ng/ml) than in females (6.2 ng/ml and 12.1 ng/ml). The mean u-PA level in males was 1.54 ng/ml which was significantly higher (p less than 0.01) than in females with 1.02 ng/ml. In post-venous occlusion studies, females had a greater mean response of 8.6 fold in t-PA activity as compared to males with a mean of 4.5 fold increase. The mean t-PA antigen response in males was 2.0 fold increase as compared to 2.6 fold increase in the females. No significant responses were seen in both sexes in either PAI activity or antigen levels when compared with the resting state. In zymography studies, free t-PA, its inhibitor complexes and u-PA were demonstrated in the euglobulin fractions of stored plasma. This study demonstrates that significant differences in t-PA, u-PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions.

Oxytocinase activity in human amniotic fluid and its relationship to gestational age.

Oxytocinase (EC 3.4.11.3) activity in amniotic fluid samples obtained from 200 normal pregnant women (mean age, 28 years) between 14 and 40 weeks of gestation and during active labor was assayed using S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN) separately as substrates. With both substrates, amniotic fluid oxytocinase activity correlated inversely with gestational age; the level of the enzyme, which was highest in early pregnancy, decreased exponentially to a minimum near term and during labor. However, whether oxytocinase activity in the amniotic fluid is of any significance for the maintenance and/or termination of pregnancy remains to be established.

Comparative study of a two dose schedule of PGE2 3 mg pessary and 1700 micrograms film for induction of labour in nulliparae with poor cervical score.

Efficacy of a two dose schedule of 3 mg pessary or 1700 micrograms film of PGE2 for induction of labour was compared in nulliparae with poor cervical score. Patient characteristics in the two groups (43 in 3 mg and 40 in 1700 micrograms group) were comparable in age, period of gestation, indications for induction of labour and in their initial cervical score. The number of patients who started labour with a two dose schedule 4 hours apart were similar in each group. The improvement of cervical score, length of labour, mode of delivery and the neonatal outcome were not different in the two groups. There was no advantage of using a film preparation over that in the form of a pessary and the use of 3 mg dose did not give significantly better results compared with the 1700 micrograms dose, in terms of obstetric or neonatal outcome.

Thyrotoxicosis in Ugandan Africans.

A retrospective 5 year study of thyrotoxicosis at Mulago Hospital, Uganda is presented. 30 cases were analysed and features pertaining to the clinical pattern are described. Comment is made on 5 cases which had associated cardiovascular abnormalities. The increased incidence of the condition in Uganda and other parts of Africa is noted. It is suggested that this may provide the opportunity for workers to follow up larger series, and assess the clinical, epidemiological and immunological aspects of the disease which could provide important clues as regards the genesis of thyrotoxicosis.

Levels of lupus autoantibodies in pregnant SLE patients: correlations with disease activity and pregnancy outcome.

OBJECTIVE: To follow the levels of lupus autoantibodies throughout pregnancy in a large cohort of pregnant SLE patients, and to examine whether they correlate with disease activity and pregnancy outcome. METHODS: 54 pregnancies in 46 SLE patients, and 70 control pregnant women were followed in the study. All patients were receiving steroid treatment. Titers of antibodies to ssDNA, dsDNA, histones, cardiolipin (CL) and phosphatidylserine (PS) were determined at the first, second, and third trimester and post-partum by ELISA. RESULTS: Overall the average levels of autoantibodies in all the patients were within the normal range, except for the average levels of anti-dsDNA antibodies which were elevated during the second trimester. Eight women (14.5%) had active disease during pregnancy, and there was a significant correlation between the levels of anti-dsDNA and the risk of disease activity (p = 0.0225). There were 7 fetal losses. There was a tendency for correlation between elevated anti-dsDNA levels, and anti-CL levels and the risk of fetal loss; however, this did not reach statistical significance (p = 0.0685, and 0.0881, respectively). There was a significant correlation between the levels of anti-dsDNA antibodies and the risk of preterm delivery (p = 0.0331). CONCLUSIONS: Pregnancy in SLE patients is associated with significant complications to both the mother and the fetus. Anti-dsDNA levels seem to correlate with the risk of disease exacerbation, and prematurity. Elevated levels of anti-dsDNA and anti-CL may suggest an increased risk of fetal loss.

Breastfeeding trends in Singapore.

About 60% of well-to-do mothers in Singapore initiate breastfeeding. This value compares favourably with the 36% recently recorded for poor mothers, but is still unacceptably low compared to the 85-95% of well-to-do mothers and 90% of poor mothers who breastfed in the 1950s and 1960s. There has been a general decline in the incidence of breastfeeding over the last 35 years. Differences between the well-to-do and poor groups were initially small. A pronounced decline in the incidence of breastfeeding among the well-to-do mothers followed; a reversal in this downward trend in well-to-do mothers over the past 10 years has narrowed, and indeed reversed, the difference between the two groups. Similar trends can be found for the duration of breastfeeding. Whilst the overall decline probably reflects increasing affluence and 'Westernization' of the population the variation between these two economic groups is probably a result of differences in education. Among the three major ethnic communities, Chinese favoured breastfeeding least and Malays favoured it most. The differences are believed to be related to cultural differences and the ability of traditional practices and beliefs among the ethnic groups to resist the modern trend towards bottlefeeding.

Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore.

The feasibility of introducing low dose (5 micrograms) hepatitis B (HB) virus vaccination at birth and again 1 and 2 months later as part of an existing primary immunisation programme of childhood, was assessed in 662 healthy newborn Singapore children. The vaccine (B-Hepavac, Menck, Sharp and Dohme) was given to three neonatal groups: those born to HB surface antigen (sAg)-negative mothers, HBsAg-positive/HBeAg-positive mothers and HBsAg-positive/HBeAg-negative mothers. A dose of 5 micrograms was compared in a randomised study with the more usual 10 micrograms dose given at the same intervals. Neonates born to HBsAg-positive/HBeAg-positive mothers were also given hepatitis B immunoglobulin (HBIg) at birth. The 5 microgram dose of vaccine was as immunogenic as the 10 microgram dose in all three groups of children studied. At 1 year, anti-HBsAg seroconversion among infants of antigen-negative mothers was 95.8% for the 5 microgram dose and 91.9% for the 10 microgram dose. Suppression of anti-HBsAg formation was not seen even when maternal anti-HBsAg was present or HBIg given. Among infants born to HBsAg-positive/HBeAg-positive mothers, passive plus active immunisation was 100% protective at doses of 5 micrograms and 10 micrograms vaccine in the newborns who were HBsAg-negative at 24 h. Seroconversion after both the 5 and 10 microgram doses of vaccine was reduced, however, to 88% in each group of infants who were already HBsAg-positive at 24 h of age. Overall, passive plus active immunisation as well as HB vaccine alone (5 micrograms dose), given within the existing but expanded primary immunisation programme of childhood, was effective in preventing infection and the chronic carrier state in newborns exposed to risk of HB virus infection during infancy.

Norplant contraceptive subdermal implants: one year experience in Singapore.

Norplant contraceptive implants are silastic implants containing levonorgestrel. This study describes our experience with 100 acceptors of Norplant implants in Singapore. There were no infections at the site after the implants were inserted. No pregnancies occurred during the first year of use. Disruptions of menstrual rhythm was the main complaint. However, the incidence of menstrual irregularities appeared to diminish with time. Implant users have tolerated this early disruption of their menstrual rhythm well and the continuation rate at the end of the year was 96.6 percent. Thus, it appears that Norplant contraceptive implants offer a highly effective means of contraception which should become well accepted in the near future.

Acceptability of Norplant-2 rods as a method of family planning.

The Norplant-2 rod system consists of two silastic rods in which levonogestrel has been incorporated with the polymer. The continuation rate at the end of five year was 62%. No accidental pregnancies occurred throughout the five years of use. The post-removal conception rate in women desiring pregnancy was 70.8% at the end of two years. The majority of acceptors were happy with the rods and 86.8% expressed the desire to have another set of implants inserted following removal of the first set. The study shows the Norplant-2 rod system to be a well accepted method of family planning.

PIP: Physicians from the National University Hospital, Singapore enrolled 100 women between December 1985-March 1986 in a 5 year study of the efficacy, acceptability, and reversibility of Norplant-2 rods. They examined them at 1, 3, 6, and 12 months and 2 times each year thereafter. All women returned. No one had an unintended pregnancy. The leading reason for removal was planning a pregnancy (24 of 38 removals). The 8 removals for menstrual problems occurred during the 1st 2 years. Of the 24 women, 6 changed their minds about having another child and used other family planning methods. 58.3% of the 24 women (77.7% of the 18 women who still wanted to conceive) were pregnant within 3 months after removal. At the end of 2 years, only 1 woman did not become pregnant (70.8% of 24 and 94.4% of 18) probably because she was experiencing subfertility since she was 44 years old. All 17 women gave birth vaginally to healthy full term infants. The physicians removed the rods from the 62 women who still had a Norplant-2 system at the end of 5 years. 87.1% (52) found the Norplant-2 system very favorable. No woman said it was not favorable. Further all 62 women were satisfied with all the information they received about the Norplant-2 system. 74.2% thought Norplant-2's ease of use/convenience was its best attribute and 24.2% said it was the low risk of pregnancy. Moreover 48.4% did not think negatively about Norplant-2. The least liked attribute was menstrual pattern changes (35.5%). 4 women complained about the removal procedure being painful, yet 3 requested a 2nd set of Norplant-2 rods. In fact, 86.8% of the women who intended to use contraception after removal chose Norplant-2 rods. Of the 9 women who did not plan to use contraception, 7 planned to conceive and 2 were widowed. In conclusion, Norplant-2 system is safe and efficient. Further it has an advantage over the Norplant-6 system--ease of insertion and removal.

Effect of Norplant implants on liver, lipid and carbohydrate metabolism.

In this study involving 100 women, the metabolic changes seen with Norplant use were evaluated. Besides a significant increase in serum bilirubin, there were no other changes in liver function to suggest possible hepatocellular dysfunction at the end of five years. Even the raised mean levels of bilirubin remained within the normal clinical range for the local population. As regards lipid metabolism, total triglycerides, cholesterol and LDL-cholesterol were decreased through the five years of Norplant use. The HDL-cholesterol showed a significant increase in the first year; it then decreased over the years to its preinsertion level at the end of five years. As a result, the HDL-cholesterol/Total cholesterol - HDL-cholesterol showed a significant increase in the first year and then decreased to almost its preinsertion value at the end of five years. The findings appear to indicate Norplant use not to be contributory to cardiovascular risk. The use of Norplant was not associated with any significant effect on carbohydrate metabolism.

PIP: Health workers at the National University Hospital in Singapore drew blood samples from 100 women prior to insertion of Norplant and at month 6, 12, 24, 36, 48, and 60 to study the effects of Norplant on metabolic function. After 5 years of use, the bilirubin level was significantly higher (50%) than preinsertion levels (p.001). This was the only significant change in liver function. Further the mean level of bilirubin and other parameters of liver function were within the clinical range for all 100 women. High density lipoprotein (HDL) cholesterol level rose considerably the 1st year (p.001), but within 2 years it fell significantly below the mean preinsertion level (p.01). At the end of the study, however, it increased to almost its preinsertion level. The HDL cholesterol/total cholesterol - HDL cholesterol increased considerably the 1st year (p.001), but decreased over the remaining years to almost the preinsertion level (p.05). In fact, it always remained above 0.200--a level below this indicated an increased risk of acquiring coronary heart disease or progression of existing disease. No significant changes in carbohydrate metabolism occurred during the 5 years of the study. The results of the lipid and carbohydrate metabolic tests indicated that Norplant does not increase cardiovascular risk and may indeed protect against cardiovascular conditions. The researchers concluded that the evidence shows that Norplant can be used more often in the future.

Effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism.

The effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism was evaluated in 100 women using Norplant-2 rods. Besides a significant increase in serum bilirubin, there was no other obvious evidence to suggest any possible hepatocellular dysfunction with the use of Norplant-2 rods. As regards lipid metabolism, decreases in total triglycerides, cholesterol and LDL-cholesterol and HDL-cholesterol were initially seen. These parameters returned to their preinsertion mean at the end of five years. As a result, the value of the HDL-cholesterol/total cholesterol - HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios remained around their preinsertion value at the end of five years. All this appears to indicate that the use of Norplant-2 rods is not directly contributory to cardiovascular risk. The use of Norplant-2 rods was not associated with any significant effect on carbohydrate metabolism.

Acceptability of Norplant implants for fertility regulation in Singapore.

The continuation rate at the end of this five-year clinical study was 60% with no accidental pregnancy occurring throughout the five years. The post-removal conception rate in women desiring pregnancy was 92% at the end of two years. The majority of acceptors described the overall experience with the implants as favourable. In fact, 75% of the women planning to use contraception after removal of the implants were going to use implants again.

PIP: The results of Norplant implants in Singapore in 1985 are reported based on clinic data from 1991. Recruitment of 100 acceptors 18-40 years old in 1985 followed the criteria established by the Population Council's International Committee for Contraception Research: sexually active and having at least 1 birth and medically safe for steroid use. The mean age was 29.5 years, average education 7.8 years, and parity average 2.1 live births. Contraceptive effectiveness was 100% for the 60 continuing for the complete 5 years. There were 40 removals, of which 25 were for planned pregnancy and 12 for menstrual problems. Of the menstrual problems, 9 had complaints of prolonged bleeding or spotting 10 days. 2 had increased menstrual periods. 1 had prolonged amenorrhea. Removals were made within the 1st 3 years. and there is support for prior findings that menstrual disturbances decrease over time. Of the 25% that discontinued to have another child, 44% conceived within 3 months of removal, 64% within 2 months, 84% within a year, and 92% within 2 years. The only 2 women not conceiving were using other means of contraception. All 22 women had full term normal vaginal deliveries; there was 1 induced abortion due to marital difficulties. Acceptor satisfaction was high at 71.2%. None considerable the experience unfavorable. Convenience and ease of use was the most desirable feature followed by the low risk of pregnancy. 6.8% found removal to be painful, but 2 of the 4 had reinsertions. 88.1% recommended Norplant to friends or relatives. 88.1% planned to use contraception after Norplant, of which 75% were going to use implants again. Of the 7 not planning on contraceptive use after removal, 2 were divorced, and the other 5 were planning a pregnancy. The authors conclude that the findings strongly support the Norplant implant system as effective and acceptable and reversible for Singaporean women. The continuation rate of 60% was comparable to other international findings.

Effect of long-term use of Norplant implants on haemostatic function.

This study describes the effects of Norplant on haemostatic function after 5 years of use in 97 women. There was a decrease in vitamin-K dependent Factors II, V, VII and reduction in fibrinolytic activity at 2 and 4 years of use. Increased platelet numbers and accelerated platelet aggregation were found throughout the 5 years of Norplant use, whilst raised alpha 2-Macroglobulin (a2-M) and antithrombin III (ATIII) antigen level were observed for up to 4 years of use. Prolonged Norplant use does not appear to activate the coagulation system and does not enhance a state of hypercoagulation.

PIP: The effect of 5 years' use of Norplant on blood clotting factors was assessed in 97 Singaporean women. The subjects were healthy, non-smoking non-alcohol drinking and non-lactating. Blood was sampled at 6, 12, 18, 24, 36, 48 and 60 months, after an overnight fast, and resting 30 minutes before venipuncture. Hemoglobin and hematocrit increased 10% in the 1st year (p0.001), fell for the next 2 years, reaching pre-insertion levels by 3 years, then increased 10% for the last 2 years. There was a significant shortening of the prothrombin time (PT) throughout the 5 years, and of activated partial thromboplastin time (APTT) for 3 years. Vitamin K-dependent Factors II, V, VII, decreased throughout the 5 years, and fibrinolytic activity decreased at 2 and 4 years of use. Fibrinogen increased at the end of the 1st year only. Platelet numbers rose 25.6% to 43.4%, and platelet aggregation to both ADP and collagen increased throughout the 5 year period. Alpha2-macroglobulin and antithrombin III antigen levels were heightened for 4 years. Most of the observed changes were different from those seen in oral contraceptive users, except for alterations in platelet function. While some of the measured clotting factors were significantly different, none were of any clinical significance, nor were these women in a state of hypercoagulation.

Effect of Norplant-2 rods on haemostatic function.

A longitudinal study on one-hundred Singaporean women using Norplant-2 rod implant for contraception and their effects on the haemostatic function was carried out. There was a decrease in vitamin K-dependent Factors II, VII and a tendency towards lowered fibrinolytic activity after prolong use of Norplant-2 rods. The results indicate that the Norplant-2 rod implant system does not contribute towards hypercoagulable state but increased platelets and accelerated platelet aggregation observed will require further study to ascertain whether there is a concomitant increase in platelet activation.

Menstrual bleeding patterns in Norplant-2 implant users.

The objective of the present study was to analyze the patterns of menstrual bleeding in Singaporean women using Norplant-2 contraceptive implants over a five-year period. Of the 100 women recruited for the study, 62 were still using the implant at the end of five years. Only 9 women discontinued for menstrual reasons and they did so within the first 21 months of implant use. Although a normal menstrual bleeding pattern was uncommon during the first three months of use, 69.4% had normal menstruation at the end of five years. Irregular bleeding was the most common form of menstrual abnormality throughout the study period. Infrequent periods and amenorrhoea were distinctly uncommon, especially after the first two years of use. The pattern of bleeding with Norplant-2 was not significantly different from that previously observed with Norplant.

PIP: To investigate the menstrual bleeding patterns among long-term users of Norplant-2 implants, 100 Singaporean women were followed for 5 years. All participants had delivered at least one child prior to implant insertion and had a history of regular menstrual periods. Monthly menstrual diaries indicating days of bleeding or spotting were collapsed into successive 90-day reference periods and analyzed for evidence of amenorrhea, prolonged bleeding (10 days or more), frequent bleeding (over four bleeding/spotting episodes per month), infrequent bleeding (less than two episodes), and irregular bleeding (bleeding-free interval exceeding 17 days). At the end of the 5-year study period, 62 women still had their implants, 9 had discontinued within 21 months after insertion for menstruation-related reasons, while 24 requested removal to achieve pregnancy. There were no pregnancies during Norplant use. Although only 9% of users experienced normal menstrual bleeding in the first three months of use, this statistic increased to 32.6%, 43.6%, 37.8%, 52.3%, and 69.4% after 1, 2, 3, 4, and 5 years of use, respectively. The most common menstrual irregularities were irregular bleeding and prolonged bleeding. Although more women had regular cycles with time, there was only minimal improvement in intraindividual variability in those who continued to have irregular bleeding. Overall, the bleeding disturbances recorded by Norplant-2 acceptors did not differ substantially from those found among users of the original Norplant delivery system.

The effects of reformulated 2-rod Norplant implant on hemostasis after three years.

Prolonged use of reformulated and the original 2-rod Norplant implants showed similar changes in most hemostatic parameters studied. Raised hemoglobin concentration and hematocrit values with not enhanced platelet activation or significant changes in platelet numbers were seen. Factor VII showed an increase from 18 months compared to the first 12 months of original Norplant implant use, while with reformulated Norplant implant, the level at 36 months was significantly higher than the first 24 months of implant use. Fibrinogen levels were significantly elevated by 36 months of both implant use. No evidence of enhanced activation of coagulation, fibrinolysis/inhibitor were observed during prolonged implant use. Overall, no significant changes in tissue plasminogen activator (t-PA) levels were observed but urokinase-like plasminogen activator (u-PA) levels were significantly reduced, indicating no enhancement of tissue breakdown. Plasminogen activation inhibitor (PAI-1) antigen levels were significantly reduced from 12 to 36 months with original Norplant implant use compared to the pre-insertion levels, while a nonsignificant decreased trend was seen with prolonged reformulated Norplant implant use. The increased levels of fibrinogen and FVII at the end of 36 months of implant use require further observation as these factors are known markers of hypercoagulation and associated with increased arteriosclerotic and cardiovascular risks. This study is on-going to evaluate the effects of levonorgestrel-containing subdermal reformulated Norplant implants on hemostasis after five years of use.

PIP: Researchers compared data on women using the 2-rod Norplant implant system formulated with the Silastic elastomer 4092 (original system) with those using the 2-rod Norplant made with a different elastomer (Q74910) (reformulated system) to examine their hemostatic effects during 36 months of use. All 33 women lived in Singapore. Both systems released the same amount of levonorgestrel at the same rate. In most hemostatic parameters, prolonged use of both 2-rod Norplant implant systems effected similar changes: increased hemoglobin concentration and hematocrit values, increased fibrinogen levels, no increased platelet activation, no increased activation of coagulation or fibrinolysis/inhibitor, no significant changes in platelet numbers, no significant changes in tissue plasminogen activator, and decreased urokinase-like plasminogen activator. Factor VII was higher after 18 months than it was during the first 12 months in original Norplant users (p 0.001). The factor VII level at 36 months during reformulated Norplant use was significantly higher than it was during the first 24 months of use (p 0.001). None of the changes common to both systems suggested tissue breakdown. Plasminogen activator inhibitor antigen levels were significantly lower during 12-36 months than preinsertion levels in original Norplant users, while they fell insignificantly in reformulated Norplant users. The increased levels of fibrinogen and factor VII at 36 months are areas of concern since they are markers of hypercoagulation and are linked to increased arteriosclerotic and cardiovascular risks. Researchers of this on-going study will later publish the two systems' effects on hemostasis after 5 years of use.

Effect of Implanon use on selected parameters of thyroid and adrenal function.

In this article, the effects of Implanon implant use on thyroid and adrenal function was compared with those of Norplant implants. In this 2-year open randomized study of 80 implant acceptors, we found that both implants may induce minimal changes in thyroid hormones and cortisol levels, possibly secondary to alterations in the respective binding globulins in the serum. These alterations in thyroid and adrenal function would have no clinical significance in healthy women. In the Norplant group, sex hormone-binding globulin levels decreased, whereas increased levels were found in the Implanon users at the end of 2 years. These findings lend support to the fact that etonogestrel, released from Implanon implants, is significantly less androgenic than levonorgestrel, released from the Norplant implants.

The effects of Norplant on clinical chemistry in Singaporean acceptors after 1 year of use: metabolic changes.

In this longitudinal study involving 100 Singaporean acceptors, the effects of NORPLANT on their metabolic function was evaluated. With respect to liver function, the results indicate possible hepatocellular dysfunction; there was a significant rise in mean serum bilirubin from 0.55 mg/dl to 0.87 mg/dl after 12 months of use (p less than 0.001). This rise could not be attributed to a skewed distribution of mean value as the difference achieved statistical significance using the paired 't' test as well as the Wilcoxon signed rank test using the median distribution. In terms of the effects of NORPLANT on lipid metabolism, we have demonstrated a significant rise in HDL-cholesterol (1.08 mmol/l +/- 0.34 to 1.13 mmol/l +/- 0.24; p less than 0.05) with significant decreases in mean serum triglycerides (1.21 mmol/l +/- 0.74 to 0.89 mmol/l +/- 0.45; p less than 0.002) and total cholesterol (5.05 mmol/l +/- 1.02 to 4.64 mmol/l +/- 0.81; p less than 0.001) after one year of use. There was also a significant rise in the HDL-cholesterol/total cholesterol ratio after 1 year (0.225 +/- 0.086 cf 0.250 +/- 0.059; p less than 0.001). As we have not incorporated a simultaneous non-pill treated control group, the observed changes in lipoprotein lipids could be attributed to extraneous factors such as diet, exercise or other environmental changes. Nevertheless, the findings though speculative indicate NORPLANT use to be non-contributory to cardiovascular risk and indeed it may be protective factor against such risks in this population. The use of NORPLANT was not associated with any significant effect on glucose tolerance after 12 months of use.

The effects of Norplant on clinical chemistry in Singaporean acceptors after 1 year of use: I. Haemostatic changes.

A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using the levonorgestrel subdermal implants NORPLANT for contraceptive purposes. At the end of 1 year of use, results from this on-going study indicate that these subjects may have an increased predisposition to thrombosis as evidenced by significant increase in platelet count and aggregability. The results also show that NORPLANT acceptors may have an enhanced potential for hypercoagulation - with a significant shortening of their Prothrombin Time and Activated Partial Thromboplastin Time and increases in Factors V and X. As previously documented, mean values for haemoglobin and haematocrit were significantly elevated by the end of 1 year. A number of other parameters achieved statistically significant differences by the end of 1 year but these were probably due to the large sample size involved and were therefore not likely to be of much clinical importance.

PIP: The association between contraceptive agents and the risk of thromboembolism is known. Norplant is a relatively new subdermally implanted contraceptive delivery system, which releases a continuous low dose of the progestagen levonorgestrel over a period of 5 years or more. The present study examines 22 hemostatic parameters in 100 healthy, nonsmoking Singaporean women after 6 months and after 1 year of Norplant use. At the end of 1 year, there was a significant increase in platelet count and platelet aggregation, both of which indicate an increased risk of thrombosis. Prothrombin time and activated partial thromboplastin time were both significantly shortened, and Factor V and Factor X levels were elevated. These results indicate an increased potential for hypercoagulation. Mean values of hematocrit and hemoglobin were elevated. There was a decrease in the level of Factor VII and an increase in antithrombin III antigen level. It is intended that this longitudinal study be continued for the full 5 years, and it is suggested that similar studies be conducted in different populations.