T.C.Anand Kumar

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.

Determining the osmolality of seminal fluid aids in the rapid diagnosis of the fertilizing potential of spermatozoa

Submitted: June 20, 1988 Accepted: November 28, 1988 osmolality of the seminal fluid causes sperm agglutination (2). Exposure of spermatozoa to hypoosmotic solutions causes swelling of their cytoplasmic membrane (3); this phenomenon has been used by Jeyendran et al. (4) to assess the fertilizing potential of spermatozoa. In the course of screening semen samples for our in vitro fertilization-embryo transfer (IVF-ET) program, we came across cases where the osmolality of the semen was significantly below the normal range observed in fertile men. Since osmolality plays an important role in sperm function, the characteristics of spermatozoa present in the hypoosmotic semen were compared with those present in the semen with normal osmolality.

Pharmacokinetics of norethisterone following its oral administration and by spraying it nasally or sublingually to male bonnet monkeys

Pharmacokinetic parameters of norethisterone (NET) were studied in eight adult male bonnet monkeys following the administration of a single dose of 300 ug. The animals were crossed over between the following three routes of administration: oral ingestion, nasal and sublingual spraying. The results indicate that NET was readily absorbed by all three routes but the Cmax and AUC of NET were significantly greater by the sublingual route. No significant difference in the t 1/2 alpha or t 1/2 beta was observed between the three routes. These findings suggest that the sublingual route offers the possibility of reducing the effective dose of NET, which is widely used for contraceptive purposes.

The value and use of different contraceptive methods

Reductions in the rates of maternal and child mortality as well as in demographic growth are directly linked to contraceptive usage. The development and availability of safer, improved contraceptives which are convenient to use could be expected to be used by a larger group of individuals and thus make an impact on reproductive health as well as on population growth rates. Such arguments have been used to support contraceptive research. This article deals with some of the developments that have occurred as a consequence of such efforts.

Reproductive endocrine effects of intranasal administration of norethisterone (NET) to women

Four consecutive menstrual cycles were studied in six healthy parous women. A solvent mixture comprising propylene glycol:ethanol:water (3:3:4) was sprayed intranasally daily using a glass atomizer between days 5 and 24 of the first (control) menstrual cycle. NET was dissolved in the solvent and similarly administered at a daily dose of 100 mcg during the second and third menstrual cycles. Nasal sprays were not administered during the fourth post-treatment cycle. Blood samples were taken during four consecutive cycles between days 8 and 15 and again between days 20 and 24 of the cycle to estimate levels of estradiol (E2), FSH, LH and progesterone (P). These studies revealed that nasal sprays of NET were well accepted and that no adverse clinical effects or menstrual disturbances occurred. NET inhibited ovulation in one cycle. The E2-induced mid-cycle rise in FSH and LH was either suppressed or inhibited in nine out of the 12 treated cycles. P levels in three treated cycles were indicative of luteal inadequacy. These endocrine effects of NET persisted into the post-treatment cycle in two cases.