INTRODUCTION:

There is a great concern of population growth worldwide such that several methods are being used to reduce both men and women total fertility rate, especially in developing countries. Overpopulation continues to be a significant contributor to environmental degradation and human suffering worldwide.⁽¹⁾Much of the current growth in the population is unintended. It is estimated that half of all conceptions are unplanned and half of the resulting pregnancies are undesired. In most cases, half of the unintended pregnancies are due to failure to use contraception, and the other half to difficulties with contraceptive use or method failure in poor nations, contraception use is further limited by restricted access to many available mthods, both economically and culturally. ⁽²⁾ Undesired pregnancies result in unwanted children who suffer disproportionately from poverty and neglect. Women have a wide range of contraceptive choices.

Research and family planning organizations have for a long time focused upon female methods of contraception because women bear a disproportionate portion of the health and economic consequences of childbearing and rearing. Consequently, women have many contraceptive choices, ranging from daily oral medications to intrauterine devices implanted every 5 years to sterilization. There are many references to plants in literature with antifertility properties. ⁽³⁾

Need for male contraception:

There are varying reasons why couples practice contraception. The reasons vary from postponing childbearing, spacing births and limiting family size as well as to have absolute freedom from childbearing. These needs usually vary depending on the type of relationship, purpose of contraception and the age of the couple.⁽⁴⁾ The current available methods on the market for men and women do not adequately meet the varied and changing personal needs of couples in their reproductive lives and in the widely different geographical, cultural, religious and service delivery settings around the world While increasing the choice available to either partner will ensure the wider availability of safe and effective means for fertility regulation, the shortcomings of currently few available male contraceptive methods are a major barrier to the involvement of men in family planning.⁽⁵⁾Current research into male contraceptives will potentially increase the equitability of family planning between males and females. This would greatly address issues of population growth and its related detrimental effects on the environment.

Male contraceptive options:

Currently researchers have focused their investigations on three general categories of male contraceptives. The first method involves the physical blockage of the vas deferens, the channel that carries sperm from the epididymis to the ejaculatory duct. The second uses heat to induce temporary sterility. The third involves medication to halt sperm production. ⁽⁶⁾

Vasectomy:

Male vasectomy is the most effective of male methods of contraception currently available. Despite its effectiveness, there are two major disadvantages that make it unattractive to many men as an option for contraception. The first is the psychological component relating to surgery. ⁽⁷⁾ Although vasectomies are relatively non-invasive, when compared to taking a pill the procedure seems drastic. The second reason is that, although vasectomies are reversible, the rate of return to normal fertility is only about 40 %. ^(
8⁾

Condoms:

Male latex condoms offer very effective prevention from unplanned pregnancy and HIV/AIDS infection. A significant drawback to condoms is their poor long-term compliance, with more than half of users reporting inconsistent use with every act of intercourse In addition; many men dislike condoms because they feel condoms diminish sexual pleasure again hampering consistent usage. However, even when used correctly, condom breakage and slippage are not infrequent, occurring in up to 2–8% of cases. ⁽⁹⁾

An ideal male contraceptive:

Development of effective, safe and acceptable male contraceptive is challenging. For it to be embraced by males it must have no effect on libido or sexual function as well as it must be reversible. The approach to development of male contraceptive can be either to inhibit the production of sperm (spermatogenesis), interference with sperm function and structure, interruption of sperm transport, interruption of sperm deposition or prevention of sperm-egg interaction. Recent research efforts have demonstrated high efficacy rates for hormonally based male contraceptives. ⁽¹⁰⁾ Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace⁽¹¹⁾. Probably, advances in herbal orally delivered contraceptives may cause optimism that these hurdles may be overcome. Historically, efforts in male contraception have lagged substantially behind development of female contraceptives due to the complexity of the male reproductive system, social/behavioral aspects and economic considerations. The last reasoning is based on the assumptions that (a) due to availability of safe and effective female contraceptives, male methods are unnecessary; (b) men are unwilling to take contraceptive pills or injections; and (c) men will not adhere to contraceptive drug regimens as careful as do women. These suppositions are in contrast to studies conducted in more than 9000 men in nine countries on four continents ^{(12, 13, 14)}. In these studies, men of all nationalities and religions indicated a willingness to use a male contraceptive if a safe, effective product was available.

The herbal male contraceptive:

Finding an oral herbal contraceptive would allow couples control their fertility without consulting a health worker, which in turn would likely markedly increase the number of couples practicing family planning. Other advantages of such a contraceptive would include the familiarity rural people in Africa have with herbal medicines, the fewer side effects associated with herbal preparations, their ready availability from local sources, and protection of privacy.

Africa is a continent endowed with an enormous wealth of plant resources. ⁽¹⁵⁾These plants have been used for several generations in traditional medicine for the treatment of different ailments. Although a few research publications are available on the constituents and biological activity of some of these medicinal plants, the development of therapeutic agents from these medicinal plants has remained a somewhat neglected subject. The study of medicinal plants in Africa has not been taken as seriously or documented as fully as in other traditional societies, such as the Indian and Chinese. Our knowledge of African medicinal plants used for reproductive purposes is rather limited and the little available information is often fragmented. Very few studies in Africa and other developing countries have focused on herbal male contraceptives. Most of the studies done are on aphrodisiacs which aim at improving the male fertility^{(16, 17, 18)}. These studies have reported the efficacy of herbal aphrodisiacs such as Mondiawhitei on improving the male reproductive function. Most of the literature on herbal male contraceptives is coming from the Chinese.⁽^19,
20). Reported the antifertility actions of an extract from Tripterygiumwilfordii both in male rats and in men. This plant's functional mechanism was by inhibiting the basic nuclear protein turnover of late spermatids, delayed spermiation, sperm head-tail separation and microfilament and membrane damage. Even though traditional medicines used as contraceptives have a long history in Africa, very few studies have been conducted to confirm their efficacy as well as establish their mechanisms of action. Some few studies in animal models have shown that herbs such as Balanitesroxburghii Phyllanthusamarus and Carica papaya seeds have antispermatogenic effects in male animal models. Table 1 summarizes some of the plants that have been reported to exert antifertility effects in different animal models. Some selected plants with proven antifertility effect are discussed below. ^{(19, 20)}

Carica papaya linn (Family - Caricaceae):

Administration of chloroform extract of Papaya seeds showed suppression of cauda epididymal sperm motility and counts in rats and suggested that contraceptive effects are mainly post testicular in nature without influencing toxicological profile and libido of animals 36. In langur monkey the extract induces long-term reversible azoospermia. An oral dose of crude ripe paw seeds in male albino rats caused degeneration of the germinal epithelium and germ cells reduction in the number of Leydig cells and vacuoles in the tubules38. Pathak et al 39 reported the sterility in rats due to total suppression of sperm motility. Verma and Chinoy40 concluded that the papaya seed extract alters cauda epididymal micro environment. It was also evaluated that it reversibly reduced the cauda epididymal tubules, which possibly retards the sperm transport in cauda epididymis 41. Manivannan et al 42 also observed ultra structural changes in the testis and epididymis of rats following treatment with the benzene chromatographic fraction of the chloroform extract of the seeds. ^(21-27)

Azadirachta indica (Family-Meliaceae):

The administration of a leaf extract of this plant has been reported to affect the structure and function of the testis and spermatozoa in male rats). Some studies have also reported the antiandrogenic effects of Azidirachtaindica leaves in male rats The ethanol extract of its bark and flowers has been shown to induce reversible infertility in male rats by interfering with spermiogenesis at the late spermatids level. Many African countries have set up research facilities to study plant medicines with the hope that the plants and their derived compound may be utilized for drug production. There is now a wide belief that standardization of plants should be given priority so that the near end products, free of toxic material can be dispensed to patients. This alternative route is shorter and much more meaningful since it takes a very long time for a drug to be developed from a medicinal plant. ^(28-34)

Abrus precatorius Linn (Family -Fabaceae) Abricin:

It has Long been claimed by Ayurvedic physicians in SriLanka that the powdered seeds of A. precatorius (Indian Liquorice) inhibit conception in humans when taken orally. Degenerative changes were reflected in testes of rats, rabbits and pres bytis monkey after administration of50% ethanolic extract of seeds. Rao reported that extract-receiving animals how ed altered sperm morphology, reduced sperm motility and metabolism, which is correlated with its decreased fertility rate. Dose dependent reduction in testicular weight, sperm count and degeneration in later stages of spermatogenesis were found in the testis of rats treated with steroidal fraction of seeds. Ratna sooriya et al found that the seed extracts caused concentration related impairment of sperm motility with the EC50 concentration being 2. 29 mg/ml. According to Sinha it caused post-testicular antifertility effects and suppressed sperm motility in cauda epididymis. ^(35-38)

Gossypol herbaceum Family-Malvaceae:

Gossypol, a phenolic compound isolated from cotton seed oil was proposed as a male contraceptive. Hadley et al found that gossypol treatment reduced the level of serum Test osterone and luteinizing hormone levels in dose and duration dependent manner. Gossypol acts directly on testes and induce sazoospermia or oligospermia. Zavos and Zavos demonstrated that gossypol blocked cAMP formation in sperm, which resulted into inhibition of sperm motility. Nairand Bhiwgade have studied the effect of gossypol on pituitary gonadal axis and found the decreased secretary activity of accessory sex glands. Bai and Shi also investigated the inhibition of T type Ca currents in mouse.

Spermatogenic cells study was carried out to examine the role of Sertolicells in the anti-spermatogenic action of two non steroidal male contraceptive compounds (CDRI-84/35 and gossypol) by evaluating their effect on some key parameters of Sertolicell function in vitro. The authors concluded that that the anti-spermatogenic action of CDRI-84/35 and gossypol is routed through Sertoli cells by disruption of important cell functions that support spermatogenesis in-vivo. However, the two compounds appear to have different course of action in Sertoli cells, ultimately leading to spermatogenic failure. ^(39-48)

Allium Sativum Family- Amaryllidaceae:

Allium sativum, or commonly known as garlic, is a vegetable species that can be classified as either a food or a medicinal herb. It is a widely used plant product that is cultivated all over the world. Garlic falls into a family of Amaryllidaceae or the genus Allium. Its closest relatives in the onion genus include the onion, shallot, leek, rakkyo and chive. Garlic and its effects on the male reproductive system has caused a tremendous amount of interest in the Andrology and reproductive field as some researchers believe it to have a beneficial influence and others believe it to have a detrimental effect on the male reproductive system. The possible reason as to why these discrepancies exist could be due to the preparation and the dosage. The daily administration of garlic powder and aqueous garlic to adult rats caused spermicidal effects and spermatogenetic arrest. However, feeding a higher garlic supplementation over a longer period of time to the adult rats caused an increase in Epididymal spermatozoa. Although an animal model was used, comparisons can be linked to a human model to the similarities in the reproductive systems of the respective models. The effect of garlic on spermatogenesis and on testis also yielded contrasting findings. Administration of garlic over a period of time showed to have histological alterations on the cells within the testes. Both the Leydig and Sertoli cells showed lipid droplets along with a decrease in volume. Spermatocytes showed interrupted nuclear development and an increase in apoptosis was also evident. ^(49-50)

Ocimum sanctum family- labateae:

The plants of genus Ocimum belonging to family Labiatae are very important for their unique properties. Ocimum sanctum L (Tulsi), Ocimum gratissium (Ram Tulsi), Ocimum canum (DulalTulsi), Ocimum basilicum (BanTulsi), Ocimum kilimands charicum, Ocimum ammericanum, Ocimum camphora and Ocimum micranthum are examples of known important species of genus Ocimum which grow in different parts of the world and are known to have medicinal properties. Ocimum sanctum is, a small herb seen throughout India, commonly cultivated in gardens. In traditional systems of medicine, different parts (leaves, stem, flower, root, seeds and even whole plant) of Ocimum sanctum, have been recommended for the treatment of bronchitis, bronchial asthma, malaria, diarrhea, dysentery, skin diseases, arthritis, painful eye diseases, chronic fever, insect bite etc. The Ocimum sanctum L. has also been suggested to possess anti fertility, anticancer, antidiabetic, antifungal, antimicrobial, hepato protective, cardio protective, antiemetic, antispasmodic, analgesic, adaptogenic and diaphoretic actions. In addition, the leaves of O. sanctum significantly altered the sperm count, motility, velocity and fructose contained in the cauda epididymis, reduce the mating behavior of both male and female albino rats.

Recent studies shown that benzene extract of Ocimum sanctum leaves induces the ultra structural changes in the epithelial cells of the cauda epididymis, its subsequent recovery, after withdrawal of treatment, in the process of spermatogenesis and fertility of male albino rats and morphological changes in the rat cauda epididymal sperms upon graded dose treatment. As there is little information concerning the influence of O. sanctum leaves on the cauda epididymal sperm at the ultra structural level, the present investigation is designed to study whether benzene extract of O. sanctum leaves could cause some of the sperm parameters, morphological alterations in cauda epididymal spermatozoa and its organelles by electron microscopic studies and fertility of male of albino rats as this medicinal plant has anti-spermatogenic and anti-androgenic like properties. ⁽^{. (51-52)}

Momordica charantia family-cucurbitaceae:

Petroleum ether, benzene and alcohol extracts of the seeds of Momordica charantia tested in rats at the dose level of 25 mg/100 g body weight for 35 days showed anti spermatogenic activity as the number of spermatocytes, spermatids and spermatozoa decreased. Increase in cholesterol level and Sudanophili clipid accumulation indicates inhibition in the steroidogenesis. Out of the three extracts, the alcohol extract was more potent in its anti spermatogenic, anti steroidogenic and androgenic activities. It has been shown that oral administration of M. charantia root extract (5 mg/ kg b. wt. /day for 60 days) showed 100% antifertility in the rats. There was marked decline in testicular germ cell population, Leydig cell number and nuclear area as comported to controls. Serum testosterone level also reduced after extract treatment^{. (53-56)}

Piper nigrum family- piperaceae:

Piper nigrum L. commonly known as black pepper belongs to family Piperaceae. The fruits of P. nigrum are not only important as a spice or flavoring agent, but have also been prescribed for cholera, dyspepsia, diarrhea, various gastric ailments, and paralytic and arthritic disorders. It mainly contains amide alkaloids, and piperine is the major active component. Oral administration of fruit powder of P. nigrum (25 and 100 mg/kg body weight/day for 20 and 90 days) to male mice of the Parkes (P)strain adversely affects sperm parameters and also caused mark edalterations in male reproductive organs. Piperine (1-piperoylpiperidine) is an alkaloid present in the fruits of black pepper (Piper nigrum), long pepper (Piper longum) and other piper species. Piperine is the major pungent substance present in these plants and is commonly used as a spice all over the world for seasoning and flavoring food. The weights of the caput, corpus and cauda regions of the epididymis significantly decreased at dose of100 mg/kg. Epididymal sperm count and motility decreased at 10mg/kg and 100 mg/kg, and sperm viability decreased significantly at100 mg/kg. Piperine could damage the epididymal environment and sperm function^{. (57-61)}

Table 1– list of the herbal plant with their part used as male anti fertility.

S. no.	Common name	Botanical name	Family	Plant part used
1	papaya	Carica papaya linn	Caricaceae	Seed
2	Neem	Azadirachta indica	Meliaceae	Seed
3	Goonj	Abrus precatorious	Fabaceae	Seed
4	Cotton	Gossypol herbaceum	Malvaceae	Seed
5	Garlic	Allium Sativum	Amaryllidaceae	Garlic powder
6	Tulasi	Ocimum sanctum	Labateae	Leaf
7	Karela	Momordica charantia	Cucurbitaceae	Seed
8	black pepper	Piper nigrum	Piperaceae	fruit
9	turmeric	Carum carvi	Apiaceae	Rhizome
10	Thunder god vine	Tripterygium wilfordi	Celastaraceae	Root
11	Bhutala	Croton roxburghii	Euphorbiaceae	Bark
12	Pudina	Menthe arevensis	Lamiaceae	Leaves
13	Cumin	Cuminum cyminum	Apiaceae	Seed
14	Long piper	Piper longum	Pipieraceae	Seed
15	Betel pepper	Trichosanthus	Cucumerina	Petiole
16	Siris	Albizzia lebbeck	Mimosaceae	Pods, bark
17	Sada-bahar	Catharanthus roseus	Apocynaceae	leaves
18	Bael	Aegle marmelos	Rutaceae	Leaf
19	Aloe vera	Aloe barbedensis	Lilliaceae	Leaf
20	Wild caper	Capparis aphylla	Capparaceae	Plant extract
21	Dill	Anethum graveolens	Umbelliferae	Seeds
22	Kirayat	Andrigraphis paniculata	Acanthaceae	Leaves
23	Vaira-danti	Barleria prionitis	Acanthaceae	Root
24	Common rue	Ruta graveolens	Rutaceae	Plant extract
25	Indian squirrel	Colebrookia oppositofolia	Lamiaceae	Leaf extract
26	behra	Terminalia bellirica	Combretaceae	Fruit extract
27	Tumba, bitter apple	Citrullus colocynthis	Cucurbitaceae	Root
28	Honeysuckled mistletoe	Dendrophthoe falcate	Loranthaceae	Stem extract
29	Bichchhu	Martynia annua	Pedaliaceae	Root
30	Surinam wood	Quassia amara	Simaroubaceae	Bark
31	Clove	Syzygium aromaticum	Myrtaceae	Flower buds
32	Nirmali	Strychno spotatorum	Loganiaceae	Plant extract

CONCLUSION:

In developing countries contraception use is further limited by restricted access to many available methods, both economically and culturally. Therefore, better access and education regarding existing contraceptives and more contraceptive options is needed. (Table 1) Studying the potency and toxicity of local plants for birth control in the folkloric medicine may generate greater confidence in and wider acceptance of herbal contraceptives. However, the search for an orally active, safe and effective plant preparation or its compound is yet to be needed for fertility regulation due to incomplete inhibition of fertility or side effects. Although a number of plants have been reported to possess cent percent antifertility activity but till date these plants have not yet come up at the level of clinical trials. Standardization of methods, quality control, data on safety and efficacy need for proper understanding of the use of herbal medicines.

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Received on 06.12.2014 Accepted on 02.01.2015

Asian J. Res. Pharm. Sci. 5(1): Jan.-March 2015; Page 59-65

DOI: 10.5958/2231-5659.2015.00010.7