CSIR’s Novel Contraceptive Drug – A Woman’s True Saheli by Dr P. Cheena Chawla

Having a baby is no joke, for it brings tremendous responsibility on the part of both parents right from the day of conception, through the next nine months and endlessly thereafter. While treading on the path of parenthood, one faces the music of bringing up a completely helpless newborn to an adult. Surely then, a couple must be mentally prepared to take up the challenge of parenting, and therefore, must avoid unplanned pregnancy.

The trauma of an unplanned pregnancy is sometimes so unbearable that the woman takes the extreme step of getting the baby aborted. Shockingly, according to an estimate of the World Health Organisation, the annual abortion rate worldwide is 46 million, a majority of which occurs in developing countries. This reflects an unmet need of millions of couples for a family planning measure that does not take away the pleasure of the nuptial knot.

Coming to the rescue of hundreds of thousands of couples, CSIR developed the world’s first non-steroidal, once-a-week oral contraceptive drug that gave women the freedom to decide when to get pregnant.  Rightly named, Saheli, this drug is indeed a true friend as it helps to avoid pregnancy without any side effects.  A product of over two decades of research at the Central Drugs Research Institute (CDRI), Lucknow, Saheli comprises a novel non-steroidal biochemical namely, ‘centchroman’. This drug is not only unique due to its composition and mode of action but it is also very convenient to take. The recommended dose is taken twice a week for the first three months, followed by once a week schedule. This drug reached the general public in India in the year 1991 and was included in the National Family Welfare Programme in 1995.  

Hormonal contraception was pioneered by Ludwig Haberlandt, an Austrian scientist who in 1921, showed that rabbits could be rendered infertile by transplanting in them ovaries from a pregnant animal that contained high levels of progesterone. By the 1930s, it was well known that high doses of sex hormones, namely estrogen and progesterone could inhibit the release of eggs. In 1957 the first oral contraceptive pill, containing both these steroid hormones, was marketed in the United States under the brand name Envoid. It was first approved for the treatment of menstrual disorders and later marketed as a contraceptive pill.  As Envoid contained a high level of hormones, there were serious side effects of this drug.

Newer generation of combined contraceptive pills that came in vogue later contained reduced levels of the steroid hormones, estrogen and progesterone, in different proportions. For example, a low dose combination pill like Mala-D was found to be safer than the high dose combination pills. Another type of contraceptive pill, that is popular today, contains only progesterone. It prevents pregnancy by increasing the cervical mucus that slows down the motility of the sperm, and also does not allow the uterine lining to develop properly.

Next in line were injectible contraceptives like Depo-Provera (Depot Medroxyprogesterone Acetate) that contain only progesterone. This high-dose progestin injection was introduced in 1969. Although a very effective contraceptive, the many side effects of Depo-Provera outweight the benefits. Several other types of progestogen-only contraceptives were later developed like Progestasert, the first hormonal intrauterine device and Norplant, the first contraceptive implant.

High dose or prolonged use of hormonal contraceptives is known to have many side effects such as menstrual disturbances, cardiovascular diseases, and body weight changes among others. Nonetheless, millions of women around the world are today using hormone-based contraceptives. The focus of CSIR scientists was, therefore, on designing a novel contraceptive drug, which had the properties of fertility regulation minus the side effects of existing steroidal contraceptive pills.

The role of estrogen-progesterone balance in the development of fertilized ovum is well known. The understanding of the subtle biochemical events that play a role in priming of the uterus for implantation of the fertilized ovum have helped in zeroing down on molecules that interfere with the process of implantation without disturbing the normal levels of estrogen and progesterone. Concerted research efforts of CSIR scientists have shown that centchroman is bestowed with dual properties of being mildly estrogenic while being a potent anti-estrogenic agent. With this unique blend of natural properties, centchroman is equipped to inhibit the fertilized ovum from implantation without disturbing the other effects of estrogen, which means that this drug does not disturb the normal hormonal balance. Thanks to CSIR scientists, centchroman is the only anti-implantation agent approved for clinical use in the world. Judicious use of this safe and effective anti-fertility drug is even poised to check population growth.

Centchroman comprises ormeloxifene, which is a selective estrogen receptor modulator (SERM). These substances are characterized by their different actions in different body tissues. In other words, SERMs selectively inhibit or stimulate estrogen-like action in various tissues. At molecular level, estrogen acts by linking itself to receptor molecules that are present on tissues that respond to this hormone.  As SERMs have a tissue selective activity, they behave like estrogen in some tissues and at the same time, block its action in other tissues.

Estrogen is, in fact, the wonder hormone that is crucial for programming a woman’s body for child birth. It prepares the womb for nourishing the fetus and promotes the glands in breast to produce milk. It also regulates the production of cholesterol by the liver, and thus safeguards the heart, protecting women from cardiovascular diseases. Estrogen even preserves bones by maintaining their required density. However, high levels of estrogen may promote breast cancer and also the cancer in the inner lining of uterus (endometrial cancer).

Exhaustive studies, in thousands of women, evaluating the use of centchroman as a contraceptive have shown that this drug is quite safe. Unlike steroidal contraceptives, centchroman does not cause nausea, vomiting or dizziness and has no adverse effects on the woman’s lipid profile and platelet function. Moreover, the contraceptive effect of centchroman is reversible and a woman can experience normal pregnancy on stopping the drug. Besides its use as a contraceptive, this drug works as an effective treatment for dysfunctional uterine bleeding. To top it all, centchroman is bestowed with a unique property of being effective against breast cancer. Multi-centric trials have shown the efficacy of centchroman in treating breast cancer patients.

Centchroman has been licensed to two companies in India. It was first manufactured by Torrent Pharmaceuticals Ltd, Ahmedabad, and marketed as birth control under the trade name Centron that was later discontinued. Torrent Pharmaceuticals now manufactures ormeloxifene under the trade name Sevista, as a treatment for dysfunctional uterine bleeding.  HLL Lifecare Limited (HLL), formerly Hindustan Latex Limited, Trivandrum, is marketing this drug under the trade name, Saheli. In October 2008, HLL launched this once-a-week oral contraceptive pill, containing the drug centchroman, in Peru under the brand name ‘Ivyfemme’, which in Spanish means ‘friendship flower’.

In yet another achievement, CDRI has developed a contraceptive cream named CONSAP from the saponins obtained from soap nuts (Reetha) of the plant, Sapindus mukorosii. Approved by the Drugs Controller General of India for its marketing and use, this local spermicidal cream is found to be quite safe on prolonged use, and can thus come handy to women to avoid pregnancy. Moreover, in one study CDRI scientists have also shown the activity of soap nuts against a protozoan parasite, Trichomonas vaginalis that causes a common sexually transmitted disease, Trichomoniasis. This endows CONSAP with both contraceptive and microbicidal properties. CONSAP has been already licensed to the Hindustan Latex Limited for its large-scale production and marketing.