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The Quest for a Herbal ContraceptiveAn oral herbal preparation would be a major breakthrough in contraceptivetechnology. Its discovery would mean that a woman could take a contraceptiveat her convenience without consulting a doctor or a nurse and there would thusbe a substantial increase in the number of women who practise family planning.The familiarity of the rural population with herbal medicines, the lower inci-dence of side-effects associated with these preparations, their ready availabilityfrom local sources and the protection of privacy are other advantages.

Throughout history references have been made to plants in India that possessantifertility properties. Indian scientists have been working to find a herbalcontraceptive since 1966 when the Indian Council of Medical Research(ICMR) published a special report on 'Plants with antifertility activity'. 1 TheCouncil's efforts have been complemented by those of organizations such asthe Council of Scientific and Industrial Research, the Councils of the Ayurvedicand Unani Systems of Medicine, the Family Planning Foundation of India, theWorld Health Organization and the National Institutes of Health, USA.

Plants that have demonstrated interesting antifertility activity in clinicaltrials include the familiar Hibiscus rosasinensis.r" Experiments carried outin 1971 at Trivandrum showed that the benzene extract of the petals of theflower inhibited implantation in 80% of female rats when it was given in adose of 100 mg on days 1-5 of pregnancy." In another study carried out atVaranasi in 1977 an anti-implantation effect was demonstrated when the totalbenzene and water-insoluble portion of the benzene extract of the flowers wereadministered to female rats in a dose of 250 mg/kg from days 1-10 of pregnancy. 3

These studies were followed by a clinical trial with the. red petals of the plantRudrapushpaka collected between October and December. The extract wasadministered to 30 sexually active women at a dose of 750 mg/day from day 7 today 22 of the reproductive cycle." None of them became pregnant.

Embelia ribes is another plant with contraceptive properties mentioned inthe ancient textbook of Ayurveda-the Yogaratnakar. It is being used today asa contraceptive by practitioners of the traditional systems of medicine in combi-nation with Piper longum and borax. When administered at a dose of 0.5 gtwice daily from days 2-20 of the menstrual cycle, it did not have any effect onthe cervical mucus, vaginal cytology, endometrial histology or on the patternof menstrual bleeding. At this dose, therefore, the combination is ineffective. 5

Earlier investigators suggested that the combination should be tried at ahigher dose of 6 g daily for 14-16 days. In a later study, Embelia ribes alone wasadministered in a dose of 2 g for five days followed by 1 g daily for another tendays. After observing the effect on 2051 cycles over four years, it was reportedthat the plant protected 95% of women from pregnancy. 6

Other plants which have been clinically evaluated have shown disappointingresults. However, constraints in the design of the trials and difficulties inobtaining a constant supply of the plant material may have been contributoryfactors. Vicoa indica, a plant known as banjhauri, is used for inducing sterilityin the village of Sukhodeora in Bihar. 7 Montanoa tomentosa, administered as atea in Mexico, induces luteolysis in women," an effect which was first describedby a Spanish monk in 1529.

The results of experimental studies on plants with reported antifertility activityhave clearly shown that some prevent the completion of pregnancy in experi-mental animals when administered from days 1 to 4 of pregnancy. They act asantifertility agents by preventing implantation of the fertilized ovum. Fourother plants have demonstrated an unequivocal anti-implantation effect inexperimental animals. These are the seeds of Davcus carota, Butea monosperma,Sap indus trifoliatis and the leaves of Mentha arvensis.i These plants now needto be tested for toxicity according to the modified shortened toxicology profileI have proposed.!" which is now accepted in most countries. Following these

200 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 6, NO.5, 1993

studies, they need to be evaluated in Phase I and II clinical trials. Scientists inthis country have worked to bring down the number of plants to be followed upfrom an initial 321 to about a dozen.

The Central Drug Research Institute, Lucknow, in collaboration with theNational Institutes. of Health, the World Health Organization and the ICMR,has screened about 3300 plant materials for antifertility activity. Antifertilityactivity has been confirmed in 67 of these and anti-implantation activity in thefollowing plants: Ferula jaeschkeana, Bupleurum marginatum, Lepidiumcapitatum, Caesalpinia sepiaria, Lonicera japonica, Juniperus communis,Lotus corniculatus, Lamium allum and Acacia farnesiana. 11-14

Chinese scientists have developed a male contraceptive from the chanceobservation that eating food cooked in unrefined cottonseed oil led to in-fertility in men.P The substance-gossypol extracted from cotton (Gossypiumherbaceum )-has been clinically evaluated in over 20 000 men but is occasion-ally associated with diarrhoea, vomiting, hypokalaemia as well as irreversiblesterility .16 The Chinese are now investigating the possible antifertility effect onmen of the plant Tripterygium wilfordii which has an antispermatogenic action.There has been less effort in that country on investigating plants affectingpregnancy in females but those being evaluated are Murraya paniculata,Mardenia koi and Gardenia jasminoides .17

From all these plants three possible types of contraceptives could bedeveloped:1. An anti-ovulatory contraceptive to complement the existing steroidal oral

contraceptives from Hibiscus rosasinensis or Embelia ribes.2. A post-coital contraceptive could be developed from the seeds of Butea

monosperma, the leaves of Mentha arvensis or from the roots ofthe Plumbagorosea, used currently by the tribal population of Orissa. (The only drugof this type available today is the recently discovered compound mifesterone(Ru486) which has an efficacyof95% when administered alone.)

3. A male contraceptive.

The results could culminate in the development of one or more herbalcontraceptives in the next two decades if the technical and managerial con-straints experienced in earlier years are removed. Difficulties in obtainingadequate quantities of material, lack of personnel trained in the standardizationof plants, a shortage of clinical pharmacologists as well as clinicians interestedin carrying out controlled clinical trials, lack of centres for carrying outtoxicological studies and the absence of long term financial support are some ofthe problems which need to be resolved. 18-20

Many of the advances in the field of research into medicinal plants such asspectroscopic procedures for looking at crude drugs and techniques for 'finger-printing' of herbal extracts are now available and have led to a renewed interestin the search for plant contraceptives. The groundwork done by Indian scientistsin looking through the maze of information available on antifertility plants aridin identifying the few which need further testing has thus become extremelyvaluable. The next step calls for development activity very different from themethods used for synthetic drugs. It also needs backing by substantialresources. Otherwise we may see the discovery by a laboratory outside thiscountry of a herbal contraceptive from an Indian plant based mainly on earlyIndian research data.

REFERENCES1 Chaudhury RR. Plants with possible antifertility activity. New Delhi:Indian Council of Medical Research,

1966. Special Report Series No. 55.2 Batta SK, Santhakumari G. The antifertility effect of Ocimum sanctum and Hibiscus rosasinensis. Indian J

Med Res 1971;59:777--81. .3 Kholkute SD, Udupa KN. Antifertility properties of Hibiscus rosasinensis. J Res Indian Med Yoga

Homeopath 1974;9:91-5.4 Tewari PV. Preliminary clinical trial on flowers of Hibiscus rosasinensis as an oral contraceptive. J Res Indian

Med Yoga Homeopath 1974;9:96--8. .

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5 Joshi J. Virkar KD. Devi PK. Effect of an Ayurvedic preparation on peripheral parameters of the menstrualcycle. Indian J Med Res 1977;66:3942.

6 Tewari PV. Sharma SK. Basu K. Clinical trial of an indigenous drug as an oral contraceptive. J Natl IntegratedMed Assoc 1976;18:117-18.

7 Chaudhury RR. Mathur VS. Sankarnarayanan P. Clinical evaluation of plant contraceptives: Translatingfolklore into scientific application. In: Dhawan BN. Agarwal KK. Arora RB. Parmar SS (eds). Pharmacologyfor health in Asia. New Delhi: Allied Publishers. 1988:432"{;.

8 Gallegos AJ. The Zoapatle I-A traditional remedy from Mexico emerges to modern times. Contraception1983;27:211-25.

9 Chaudhury RR. A tale of six plants. In: RR Chaudhury (ed). Lectures in contraceptive pharmacology.Chandigarh:Arun and Rajive , 1981 :3&-52.

10 Chaudhury RR. Controversies in the clinical evaluation of 'antifertility plants. In: turner P (ed). Clinicalpharmacology and therapeutics. New York:Macmillan. 1980:474-82.

11 Drugs and pharmaceuticals-Current R&D highlights. Fertility regulation: Female contraceptives.Lucknow:Central Drug Research Institute. 1993:16:52-3.

12 Satyavati GV. Pharmacology of medicinal plants and other natural products in current research. In: Das PK.Dhawan BN (eds). Current research in pharmacology in India (1975-82). New Delhi:Indian National ScienceAcademy. 1984:11946.

13 Chaudhury RR. Plant contraceptives: Translating folklore into scientific application. In: Jelliffe DB. JelliffeEFP (eds). Advances in internationalmaternal and child health. Oxford:Oxford University Press. 1985;5:58-74.

14 Kamboj YP. A review of Indian medicinal plants with interceptive activity. Indian J Med Res 1988;87:33&-55.15 Qi~n SZ. Hu JH. Ho LX. Sun MX. Huang YZ. Fang JH. The first clinical trial of gossypol on male antifertility.

In: Turner P (ed). Clinical pharmacology and therapeutics. New York: Macmillan. 1980:489-92.16 Qian SZ. Gossypol-hypokalaemia interrelationships. In: Qian SZ. Waites'GMH (eds). Proceedings of a

WHO-PRC symposium. Beijing:The People's Publishing House. 1990:9-14.17 Pei-Gen X. Gong WN. Can ethnopharmacology contribute to the development of antifertility drugs?

J Ethnopharmacoll991 ;32: 167-77.18 Chaudhury RR. Experience in research on plants with antifertility activity. In: Gupta SK (ed). Immunology-

Perspectives in reproduction and infection, New Delhi:Oxford and Indian Book House. 1991 :271"{;.19 Chaudhury RR. Herbal medicine for human health. New Delhi:World Health Organization. 1992.20 Chaudhury RR. Plants with antifertility activity. In: Drugs 'andpharmaceuticals. Current R&D /lighlighlS.

Fertility regulation: Female contraceptives. 1993;16:1G-J3.

R, R. CHAUDHURY

National Institute of ImmunologyNew Delhi

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