On conception and contraception: The story of Saheli

Persistence: Dr. Nitya Anand’s team synthesised and tried a variety of molecules for anti-fertility activity. They hit upon the right candidate in 1971.  

Birth control, or deciding whether to have a baby, is at once a personal decision and a societal one. The woman must have a say in this, since it will affect her health, welfare, freedom of choice and way of life. A huge population increase will affect the resources of the society. Individual freedom and societal concerns are at the two ends of the spectrum, just as conception and contraception are. While the decision to have a baby should be left by and large to the woman, population control has become a national policy since a burgeoning population drains the food supply, standard of living, economic and social growth.

Through the ages, several methods have been adopted for contraception. Many devices - implants, female and male condoms and surgical sterilisation of males and females - have been used. But the safest (and least intrusive) is the use of chemical molecules, or “pills” in common parlance, which interfere with the biological steps involved in pregnancy. While it had been known that certain steroid molecules play a role in inhibiting crucial steps in the process, it was in 1951 when the organic chemist Carl Djerassi, along with his co-workers George Rosenkrantz and Luis Miramontes, came out with an inexpensive synthesis of the molecule called norethindrone, that the first birth control “pill” was born. This, in retrospect, was a revolutionary step that has helped many millions of women make personal decisions about having a baby or not.In the female, what this pill does is to inhibit ovulation or the release of the egg. In addition it also tends to make the vaginal fluid thicker and more viscous. As a result the sperm from the male is unable to meet the egg and fertilize it. An important point about using the pill is that it must be taken daily. Quitting it for even 2 weeks could lead to pregnancy upon mating. In addition, in many women, daily intake also leads to vomiting, nausea and bleeding between periods, since the steroid component in the pill can lead to some more unpleasant complications in some women. There was thus room for better pills.

The successful Indian effort

The Indian government, in the 1960s, called upon Indian laboratories to come up with alternate birth control pills. And Dr. Nitya Anand and his team at the Central Drug Research Institute (CDRI), Lucknow, rose up to this challenge and worked on it. Analysing earlier publications of relevance, they found a lead in a molecule called ethamoxytriphetol (alias MER-25) which showed, among other properties, anti-fertility effect in animals. But it was discontinued due to its low potency and some undesirable nervous system side-effects.

Organic chemists are molecular sculptors and architects. Nitya Anand and his colleagues, starting with MER-25 as the base, synthesised a variety of molecules and tried each of them for anti-fertility activity. After several attempts, they hit upon the right candidate in 1971. Its chemical structure is shown in the accompanying figure. Since it belongs to the chroman family and was made at the Central Drug Research Institute, they christened it Centchroman.

In contrast to the Djerassi pill, the Lucknow pill has several distinct features and advantages. 1. It need not be taken daily. Since it stays well absorbed in the body for over 170 hours, a weekly dose suffices. 2. It does not affect ovulation (and thus not disturb any hormonal balance) but .prevents implantation, the key step in pregnancy. 3. It can be taken even after sexual intercourse, thus useful even in cases of rape. 4. Since it has no steroidal component, the associated side-effects are absent. 5. Upon discontinuing the drug, fertility can be regained, thus making it suitable for spacing children.

After the obligatory clinical trials, first on animals and then on women, Centchroman was approved by Indian authorities in 1990 and licensed for manufacture by Hindustan Latex Life Care, and by Torrent Pharma, with the name Saheli (girl friend). Saheli is now part of the National Family Planning Programme as an oral contraceptive pill. And WHO has approved and assigned it the technical name ormeloxifene, which is now sold the world over as Novex-DS, or Sevista

One drug, many effects

Often, one notices that a given drug has benefits against more than one illness. This is true of ormeloxifene too. It is effective not only against conception, but also has anticancer action (against breast, ovarian and head and neck cancer) and against bone desorption (osteoporosis). Saheli is a friend which guards against several problems!

To end with a human note about two great men: Carl Djerassi and his mother fled their native Austria, evading the Nazis extermination of Jews, and landed in New York in 1939, where their last $20 was swindled. Djerassi rose from this penniless youth to remarkable heights as a creative chemist and an excellent writer. And Nitya Anand, studying in Bombay in 1947, persuaded a plane to fly to his native Lyallpur (now in Pakistan), had the seats removed and packed his parents and their neighbours in it, and had it flown to India, saving them from the savage Partition riots. Several of us owe the swift rise in our early careers to his throwing open his laboratory facilities and professional advice. The Saheli man has been a true Sahayak.

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Printable version | May 15, 2021 7:23:48 AM |

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