Katayun Virkar

Effect of contraceptive steroids on human lactation

Biochemical studies to detect changes occurring in the composition of mothers milk from the initiation of proper lactation to weaning were done in a group of 36 postpartum women, volunteers who were either using the conventional contraceptives or taking a low-dose combination pill, a low-dose progestational compound, or a 3 or 6 monthly injection as a mode of contraception. Apart from a significant increase in the protein content of milk and a slight increase in the quantity, the 3 monthly injection group behaved exactly like the control. On the other hand, the 6 monthly injection group showed a significant increase in quantity but with a significant decrease in protein, fats, and calcium. The low-dosage progestogens group showed a significant decrease in the quantity of fats and the calcium content of milk, but, surprisingly, the addition of 10 micrograms of estrogens to the low-dosage progestogen indicated a pattern almost similar to the control.

The effect of oral contraceptives on concentrations of various components of human milk.

Abstract Clinical studies to detect the changes occurring in the quality of mothers milk were carried out with: 1. (a) Combination type oral contraceptive, and 2. (b) Low dosage progestogen alone. Although both types of contraceptives were instrumental in bringing about decreases in protein, fat and calcium content of milk, only the decrease registered with combination therapy was found to be statistically significant.

RELEASE OF 19-NOR-TESTOSTERONE TYPE OF CONTRACEPTIVE STEROIDS THROUGH DIFFERENT DRUG DELIVERY SYSTEMS INTO SERUM AND BREAST MILK OF LACTATING WOMEN

The release of contraceptive steroids through different drug delivery systems into serum and breast milk was investigated in a group of lactating women. Four women in each group were taking either a low dosage progestogen compound like norethisterone (NET) 350 micrograms or d-norgestrel (d-Ng) 50 micrograms alone or low dosage combination pills containing NET 1 mg or d-Ng 150 micrograms with 30 micrograms ethinyl estradiol (EE2) or a biodegradable implant containing 25 mg NET or d-Ng. Peak levels in plasma and milk were seen in oral contraceptive users around 2 hours. Of the two low dosage progestogen compounds, d-Ng was below the detection limit in milk within 4 hours whereas NET was still detectable at the 24-hour interval. In contrast to this, because of the larger quantity of steroids in the combination pills, the NET/d-Ng levels in serum as well as in milk were high throughout the 24-hour period. With the subdermal route because of the sustained low release of the drug from the biodegradable implants, the levels in milk were below the detection limit within a day with d-Ng and within a week with NET.

Serum prolactin levels in women using copper IUDs

Serum prolactin values in 40 women using various types of copper devices for different durations of use are presented. The values indicate that the serum prolactin level is higher in women using copper intrauterine devices when compared to control group (statistically significant, P < 0.05 and P < 0.002 in lactating and non-lactating groups). The duration of use of IUD or the history of previous use of hormonal contraceptives did not affect the serum prolactin levels. A prospective study correlating the use of IUD and prolactin levels is next proposed.

Effect of contraceptive steroids on serum lipids.

Serum triglycerides, free fatty acids, phospholipids, and cholesterol were estimated in groups of women who were taking either norgestrel, megestrol acetate, daily combination tablet, once-a-month pill, or once-a-month injection as a method of contraception. These estimations were done prior to and during therapy at specific times over a period of 2 years. A significant reduction in serum lipids was observed in women taking norgestrel. The women on megestrol acetate showed practically no changes. All the lipid fractions were significantly elevated in women taking combination pills. Raised serum cholesterol was observed in women receiving once-a-month injection.

Effect of steroidal contraceptives on antibody formation in the human female

Abstract The antibody response to tetanus toxoid was studied in female subjects receiving various forms of steroidal contraceptives as compared with that in control subjects using conventional contraceptives and an IUCD. It was observed that the immune response in groups using steroidal contraceptives was considerably lower than that of the control.

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.

PRESENCE OF ELEVATED CIRCULATING LEVELS OF LH DURING THE PRE-MENSTRUAL PERIOD IN SOME COPPER IUD USERS AND THE POSSIBILITY OF THEIR CONFUSION WITH hCG

A heterologous radioimmunoassay (RIA) capable of discriminating between LH and hCG was used to measure LH levels in sera obtained during the pre- and post-menstrual periods from 80 women bearing copper intrauterine contraceptive devices (IUD). hCG levels in these samples were also estimated by use of a homologous beta-hCG radioimmunoassay and a radioligand-receptor assay. Only two IUD users during the pre-menstrual period had detectable, but low hCG levels. However, LH levels, as estimated by specific RIA, in the serum of these two women were elevated to a level that would cause detection at low levels in the hCG assays. The data thus provide direct evidence to indicate that the positive hCG levels observed by others during the pre-menstrual period in some copper IUD users could be due to the interference in hCG assays by elevated LH.

Thyroid functions of women taking oral contraceptives

A study to assess thyroid status and excessive weight gain among women taking oral contraceptives found a correlation between the percentage of free thyroxine and weight gain. Serum percentage of iodine uptake, total thyroxine, free thoraxine, and weight changes in 38 women taking combination oral contraceptives and 27 taking low dosage progestagens were studied. No change in the absolute free thyroxine levels were observed, although combination oral contraceptives caused an increase in total thyroxine and a decrease in the percentage of free thyroxine. Changes occurring in percentage of free and total thyroxine could be related to increases in thyroxine binding proteins. Low dosage progestogens showed no change in any of the thyroid tests studied. A lowering of the 24-hour uptake by the thyroid gland and weight gain with combination oral contraceptives were observed.

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 fortnights 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 weeks 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.