Population management is essential for any country. India's population stands second in the world and is growing rapidly. Oral contraceptives are preferred choice for birth control/family planning in women as it prevents the undesired or unwanted pregnancy. The oral contraceptives available are hormone (steroids) based and may interfere in the normal hormonal signalling as they need to be consumed daily.
CSIR-Central Drug Research Institute's (CSIR-CDRI) developed centchroman/ormeloxifene, which is non-hormonal (non-steroid based) in nature and is consumed once a week. There are several advantages of Chhaya/Saheli over hormonal oral contraceptives. Chhaya/Saheli has no side effects like vomiting, nausea, and weight gain. In addition, it can be taken by women of all ages (Reproductive age) and is also considered safe for use among breastfeeding women. This makes Chhaya/Saheli a better choice among all oral contraceptives for family planning.
The development of Chhaya/Saheli goes back to the 1960s when responding to the Government of India's need for an effective family planning/birth control pill indigenously, CSIR-CDRI, Lucknow took upon the task to develop the indigenous non-hormonal contraceptive pills. Dr. Nitya Anand and his team at CSIR-CDRI embarked on the journey to develop the pill.
Among several chemicals/compounds, Centchorman (Ormeloxifene) was derived from benzofuran and ethamoxytriphetol (alias MER-25) compounds as an orally taken birth control/family planning drug after several years of perseverance and hard work of Dr. Nitya Anand & team in 1971. The Centchroman was tested in laboratory experimental animals, rats, dogs, and monkeys for preclinical (before human use) contraceptive purposes. Further, the preclinical harmful effects/toxicity have also been tested on laboratory experimental animals such as rats, beagle dogs, rhesus monkeys, and rabbits and found safe.
There were several clinical trials (safety of a drug or chemical) in women before it was approved for general population use by the then competent authority of India Drug Regulatory Guideline in 1990. Clinically, 30mg once in a week Saheli/Chhaya (centchroman drug) pill efficacy was tested in women. In the Phase-I clinical trials of centchroman/ormeloxifene, single or multiple-dose investigations were conducted in healthy women volunteers as per the Drug Regulatory Guidelines. They were found very useful without any side effects. After that, dose-ranging studies and clinical trials were conducted in healthy women with regular monthly periods/ menstrual cycles. For the once-in-a-week dose calculation, a total of about 1000 volunteers were involved for nearly 7000 months/monthly cycle (total) of use. Saheli/centchroman/ormeloxifene use at 30 mg weekly dose demonstrated best contraceptive efficacy without any significant side effects except the delayed menstrual/monthly cycles in 8% healthy volunteers, but the delayed monthly cycle was normalized while continuing the use of Saheli.
Subsequently, during 1981-1982 Phase-III multicentric clinical trial for 30 mg once a week dose was conducted with 909 women volunteers of reproductive age with 1 or 2 living children in 5 Family Welfare Centres in Lucknow and 07 Medical Colleges in the State of Uttar Pradesh. The participants/volunteers have been covered for 12828 months and 11448 monthly cycles with acceptable pregnancy protection (Pearl Index: 3.76). The Pearl Index is a statistical estimation of the number of unintended pregnancies in 100 women in a year of exposure to contraceptive pills. The lower pearl index is considered better. During clinical trials, no adverse effect was seen except that the women's monthly /menstrual cycle was delayed (~45days) in only 8 % of cases, but was restored to normal in due course in response to drug discontinuation.
Phase-II/III trial's assessment in over 2000 women participants/ volunteers of reproductive age who have used Saheli/Chhaya/Centchroman for about 25000 months showed the acceptable pregnancy protection with Saheli 30 mg weekly or higher doses and 30 mg biweekly-cum-weekly dose schedule. Thus, the 30 mg biweekly-cum-weekly dose of Saheli/Chhaya/ Ormeloxifene/Centchroman schedule was suggested for pregnancy protection and cycle control and therefore has been recommended for wider clinical use with DCGI permission.
The contraceptive action of the active ingredient of Saheli /Chhaya, centchroman, causes asynchrony in preparing the uterus (Womb) for the blastocyst implantation, which is otherwise required for pregnancy/conception. The Saheli/Chhaya gives an edge over the other contraceptives or birth control pills consumed once a week and non-hormonal (Steroidal). HLL launched the Saheli/Chhaya in 1991. Centchroman has been in the market for over 30 years and more development has taken place in CSIR-CDRI.
After the clinical trials, Saheli (Centchroman) was launched in 1995 in the National family program and is available free of cost at the primary health care centre and the various pharmacy stores all over India. In 2016, the Ormeloxifene/Centrchroman as Chhaya has been reintroduced as part of "National Family Planning Programme and distributed or delivered home-to-home by 'ASHA' NGOs.
CSIR-CDRI, in collaboration with Cipla Ltd., Mumbai is planning to explore the possibility of bringing a new generation of ormeloxifene/centchroman (Saheli) with enhanced efficacy and at a lower dose.
Drs. Rajesh Kumar Jha, Arun K. Trivedi and Sanjeev Yadav
CSIR-Central Drug Research Institute, Lucknow