The effect of combination and low dose progestogen oral contraceptives on serum lipids.

Fasting serum triglyceride, free fatty acid, phospholipid, and cholesterol levels were determined in women who were taking either combination or low dose progestogen oral contraceptives. The contraceptives used were: ethynodiol diacetate and ethynyl estradiol; norgestrel and ethynyl estradiol; norgestrel; and megestrol acetate. Serum lipids significantly increased in women taking combination pills. They significantly decreased in patients taking norgestrel, while they remained almost unchanged in patients taking megestrol acetate. This decrease varied with the type of progestogen used in continuous low dosage therapy. The confusion when interpreting the results from different reports on the effects of oral contraceptives on serum lipids will be reduced if proper attention is given to the types of steroid used.

Biochemical studies with once-a-month contraceptive pill containing quinestrol-quingestanol acetate.

PIP: Biochemical studies with a once-a-month contraceptive pill containing 2 mg quinestrol and 2.5 mg quingestanol acetate were undertaken during a period of 24 months. The 1st pill was given on the 2nd day of the menstrual cycle and the 2nd on the 22nd day of the same cycle; thereafter the pills were given every 28th day from the last pill. Blood samples were obtained before therapy and after 6, 12, 18, and 24 pills. Hemoglobin, packed cell volume, liver function tests, and serum proteins were not markedly altered. There was a significant (p less than .001) elevation in serum triglycerides, free fatty acids, phospholipids, and cholesterol after the ingestion of 6-12 pills in 17 women who were continuously followed for 2 years; however, serum triglycerides and phospholipids were less after the ingestion of 12 pills than after 6 pills. It appeared that these changes in serum lipids were similar to those reported in women taking daily combination pills. In no case did the serum lipids exceed the upper limit of normal. The drop-out rate was high after 12 pills. Th nonacceptability was of greater significance, therefore, than the metabolic effects in these trials.^ieng

Serum bile acids in women taking combination contraceptives.

A longitudinal study in 60 women was undertaken to observe the changes, if any, in serum bile acids after taking oral combination pills containing either 50 or 30 microgram of ethinyl estradiol. The women were followed up to 12 months. Serum bile acids (cholyglycine conjugates) were estimated by radioimmunoassay. The combination contraceptives had no appreciable effect on serum bile acids.

PIP: 60 women attending family welfare clinics in India were recruited for a longitudinal study designed to test for changes in serum bile acids after oral combination contraceptives were administered which contained either 30 or 50 mcg of ethinyl estradiol. The women were divided into 2 groups according to the drug (dose) ingested, and fasting venous blood was collected between Day 10 and 20 of the menstrual cycle. Blood collection was repeated at either 1, 3, or 6 months after taking pills, and all women were again followed-up at 12 months. The serum bile acids (cholic acid conjugates) were measured by radioimmunassay. The sensitivity of the assay was .06 mcmol/liter. Recovery studies were carried out by adding cold glycocholic acid and recovery was 95%. The interassay coefficient of variation for a plasma pool with a concentration of 1.68 mcmol/liter was 5.4%, whereas the intrassay coefficient was 6.2%. Serum bile levels in women taking the combined preparations showed no significant changes in the levels, up to 12 months of intake, in both groups.

Clinical performance and endocrine profiles with contraceptive vaginal rings containing a combination of estradiol and D-norgestrel.

Contraceptive vaginal rings (CVRs) impregnated with a combination of estradiol and d-norgestrel were studied in 39 women. The rings were inserted as three weeks "in" and one week "out" schedule to allow withdrawal bleeding. Ovulation was inhibited in all cycles and promptly resumed on completion of the treatment cycles. Bleeding control was excellent. Incidence of breakthrough bleeding was 2.11 per cent in 273 cycles studied, with 89 per cent of the cycles within the acceptable range (25 - 35 days). Levels of estradiol after an initial rise were maintained between 50-100 pg/ml and, d-norgestrel levels were relatively constant between 1.8-3 ng/ml during the period while the ring remained in situ. Clinical acceptance was good. The main problem encountered was of spontaneous expulsion of the ring in the toilet, which might be due to the squatting toilet habits of Indian women and laxity of vaginal wall.

PIP: Contraceptive vaginal rings (CVRs) impregnated with a combination of estradiol and d-norgestrel were studied in 39 women. The rings were inserted on a 3 weeks "in" and 1 week "out" schedule to allow withdrawal bleeding. Ovulation was inhibited in all cycles and promptly resumed on completion of the treatment cycles. Bleeding control was excellent. Incidence of breakthrough bleeding was 2.11% in 273 cycles studied, with 89% of the cycles within the acceptable range (25-35 days). Levels of estradiol after an initial rise were maintained between 50-100 pg/ml and, d-norgestrel levels were relatively constant between 1.83 ng/ml during the period while the ring remained in situ. Clinical acceptance was good. The main problem encountered was of spontaneous expulsion of the ring in the toilet, which might be due to the squatting toilet habits of Indian women and laxity of the vaginal wall.

Phase I comparative clinical trial with subdermal implants--bioabsorbable levonorgestrel or norethisterone pellet fused with cholesterol.

The potential for antifertility effect of two bioabsorable pellets, one containing norethisterone (NET) and the other containing levonorgestrel (LNG) fused with cholesterol, was studied in a group of healthy, menstruating but sterilised women. The pellets weighed approximately 30 mg and contain 85% steroid and 15% cholesterol. A single NET pellet was inserted in 4 subjects, out of which 2 were also studied for steroid pattern in blood. After reaching peak levels within 48 hours, the plasma NET levels declined gradually within a fortnight's time, and thereafter, ranged between 200 to 700 mg/ml up to 90 days post-insertion. After this period, occassional spurts of NET release were seen. Bleeding pattern was studied in 37 cycles; mid-luteal progesterone (P) estimation was done in 16 cycles, mid-cycle cervical mucus was studied in 27 cycles and post-coital test (PCT) in 7 cycles. Cycle length with pellet insertion was of 25 to 37 days duration except one cycle of 55 days duration. All cycles studied during the treatment were ovulatory (P greater than 5 ng/ml) and no consistent effect was observed on cervical mucus as well as on PCT. Thus, a single NET pellet does not seem to have a reliable contraceptive potential. A single LNG pellet was inserted in 8 subjects, and steroid patterns were studied in 6 women. Peak levels of LNG were reached within 24 hours of pellet insertion and the levels fell gradually in a week's time. Thereafter, LNG levels ranged between 100-400 pg/ml up to 8 months. In contrast to the observation with NET pellets, only one subject showed frequent spurts of LNG release until the 4th month of treatment. Bleeding pattern was studied in 90 cycles, P was estimated in 52 cycles, mid-cycle cervical mucus studied in 55 cycles and PCT done in 26 cycles. Breakthrough bleeding (BTB) occurred on 15 occasions, 11 episodes being in 2 subjects. Cycle length varied between 21 to 42 days. The LNG pellet did not exert a consistent effect either on ovulation inhibition or cervical mucus or PCT. In their present form, therefore, a single LNG pellet also does not appear to have a reliable contraceptive effect.

A multicentric evaluation study of an indigenously prepared cost effective prototype pregnancy test.

A multicentric evaluation of an indigenously developed pregnancy detection kit (named Preglisa) based on urinary human chorionic gonadotropin (hCG) detection was carried out at 12 centres where the outcome of the kit was compared with the existing parameter (e.g., ultrasonography, clinical judgement, serum beta hCG levels) used by the centre for confirmation of the pregnancy. The specificity, sensitivity and accuracy of the kit were 98.05, 98.7 and 98.69 per cent (n = 382) when results of Preglisa were compared with those of non-immunological tests. When compared with commercially available kits, sensitivity was 97.9 per cent, specificity was 97.2 per cent and accuracy was 97.94 per cent (n = 155). The kit is cost effective with a sensitivity of 300 mlU/ml and is recommended for detecting pregnancy 35 days after the last menstrual period thus fulfilling the general requirement in the Indian situation.

Feasibility of determination of fertile period in Indian women based on urinary hormone estimations.

Baseline data available on the excretory profiles of estrone giucuronide (E(1)G), pregnanediol glucuronide (PdG) and luteinising hormone (LH) on human menstrual cycles (n=104) was retrospectively analysed for identifying the limits of fertile period (FP) to be used as natural method of family planning. The limits of fertile period are suggested based on centile distribution of E(1)G and PdG levels during defined phase of menstrual cycle. Two approaches, which do not involve any mathematical calculation are suggested. In approach A, fertile period is said to have started when E(1)G value of 35 ng/ml is reached and is said to have ended when the PdG value of 2 µg/ml on two consecutive days is obtained. The criteria were applied to 30 test cycles in whom authentic fertile period was identified based on excretory profiles of E(1)G, PdG and LH throughout the menstrual cycles. When approach A was followed the authentic fertile period was covered in 27 cycles giving an accuracy of 90% with a mean fertile period length of 9.11+1.9 days. In approach B, the cut off limit of E(1)G value was increased to 55 ng/ml in order to reduce the days of abstinence. Though the length of the fertile period was reduced to 7.2+1.5 days the accuracy of the approach was 66.6%. Thus the approach A which has accuracy of 90% may appeal to determined couples who wish to practice family planning by periodic abstinence or restrict the use of barrier methods.

Lactoferrin in cervical mucus as a biochemical marker for inflammation.

Lactoferrin, an iron-binding protein, has been proposed to act as an anti-infective agent and has been used as a diagnostic marker in several inflammatory disorders. A sensitive enzyme-linked immunosorbent assay developed earlier was used for lactoferrin estimation in cervical mucus. A brief study was undertaken to observe if lactoferrin is detectable in cervical mucus and to correlate its level with reproductive tract infection, if present. One hundred and twelve cervical mucus samples were collected from healthy as well as infected females. Some of these females were using CuT-200 intrauterine copper devices for contraception. Women were at different phases of their menstrual cycle. The presence of detectable amount of lactoferrin in cervical mucus was confirmed. The average level of lactoferrin in cases either with clinical symptoms of cervicitis or with proven infection by PAP smear was significantly (t=7.6, P<0.01) higher than the normal controls. CuT users have higher (P<0.01) mean level of lactoferrin than corresponding non-users.