Tripterygium wilfordii, or lei gong teng, is a twining vine in the botanical family Celastraceae common to southern China. T. wilfordii and its botanical cousins T. hypoglaucum and T. regeli have been used in traditional Chinese medicine for over 2000 years, treating everything from fever and chills to edema and carbuncles. More recently it has been used to treat rheumatoid arthritis, chronic hepatitis, chronic nephritis, and several skin disorders.
|T. wilfordii is a vine common to southern China.|
Some men given T. wilfordii by their doctors are not able to conceive children. T. wilfordii’s contraceptive effect has been anecdotally known in China for many years; the first published finding came in 1982. A derivative of T. wilfordii could be an effective pharmaceutical alternative to hormonal contraceptives.
Most of the current studies on Tripterygium extracts take place in China, under the auspices of the Jiangsu Family Health Institute and Beijing and Shanghai ’s Institute of Materia Medica. A group of researchers at Harbor-UCLA’s Medical Center has also investigated one of T. wilfordii’s derivatives, triptolide.
How does it work?
T. wilfordii has not been tested in men as a contraceptive. What we know about its contraceptive effects comes from studies on rodents and retrospective studies of men taking a Tripterygium preparation for some other medical reason. These studies show that low doses of various Tripterygium preparations produce significantly lowered sperm density, with the remaining sperm incapable of swimming effectively. One study suggests that, like nifedipine, T. wilfordii derivatives may act as calcium channel blockers (Bai 2002). Much current research is focused on establishing the mechanism by which the plant affects fertility and investigating potential toxicity and side effects.
How is it delivered?
In traditional Chinese medicine, men prescribed some form of Tripterygium would make a decoction by simmering peeled, dried roots of the plant for at least an hour. Depending on the malady being treated, a doctor would prescribe 15-25 grams of Tripterygium prepared in this way each day. Researchers have found that a decoction is an effective contraceptive at one-third of this dose, or 5-8 grams per day (Qian 1987).
Although the dried roots are commonly available in Chinese pharmacies around the world, Researchers do not expect that preparing a decoction everyday is a practical way to deliver a male contraceptive. They are investigating a number of different Tripterygium preparations as possible contraceptives. These preparations would most likely be delivered in the form of a tablet or pill.
What side effects are expected?
The doses of T. wilfordii root decoction used to treat arthritis or skin diseases can cause a host of side effects, including gastrointestinal distress and suppression of the immune system (Qian 1987). But a decoction is not under consideration as a male contraceptive; researchers are investigating half a dozen extracts of varying purity. Studies of the immunosupressive effects of the derivative compounds use doses “5-12 times their anti-fertility dosage” (Zhen 1995).
Individual evaluation of each of the extracts is time-consuming and expensive. Although there is no consistent testing program, various extracts have passed mutagenicity and toxicity testing. Researchers are continuing to investigate Tripterygium’s immune suppression mechanisms. One surprising result came from an study of tripchlorolide, which shows opposite effects on the immune system depending on the dose. Mice given a low dose of tripchlorolide showed enhanced immune function, while mice given a high dose showed signs of immune suppression (Lou 1990).
All studies of the various Tripterygium preparations have shown that they do not affect libido, body weight or hormones, which are some of the undesirable side effects associated with hormonal male contraception.
To better understand the mechanism of action of Tripterygium, researchers are isolating the various active compounds to test them individually. The World Health Organization helped coordinate this collaborative research effort (Waites 1999). At least six of the compounds isolated to date have a contraceptive effect: triptolide, tripdiolide, triptolidenol, tripchlorolide, 16-hydroxytriplide and a compound known only as T7/19 (Zhen 1995). Researchers are still working to fully describe the effects of each of these compounds. They are all different, and so they are described separately below.
One of T. wilfordii’s botanical cousins — T. hypoglaucum — shares its potency as a contraceptive. A study of T. hypoglaucum’s effect on men’s sperm was one of the original findings of the Tripterygium family’s contraceptive effect. The study showed that a decoction of T. hypoglaucum could provide reversible contraception.
Men using 15 grams per day of a T. hypoglaucum root decoction for arthritis had an average sperm density less than 1% of normal. Only 26% of the remaining sperm were able to swim, but even these would not have been able to reach an egg because their movements were too uncoordinated (known as non-progressive motility). The 13 men in this study had taken T. hypoglaucum for varying lengths of time, mostly between two months to two years, with one man having taken it for ten years. Eight of the men stopped treatment; their sperm count and motility returned to normal within 6 to 12 months (Qian 1988).
Glycosides of T. wilfordii
Another common Chinese medical preparation of T. wilfordii is a tablet containing 10 milligrams of extracted compounds from the root. These tablets contain a mix of all the active compounds of the plant in a concentrated form, and are called glycosides of T. wilfordii (GTW) or lei gong teng pian. Studies of GTW showed that it could provide reversible contraception at doses three to four times smaller than those commonly prescribed for medical conditions.
In studies on rats, low doses of GTW caused reduced sperm counts and deformed sperm incapable of swimming, but no effects on body weight, mating behavior or hormones (Qian 1986, Lu 1990b).
Twenty-six men using one third of the normal dose of GTW, or 20 milligrams per day, to treat psoriasis showed a rapid onset of the contraceptive effect. Within one month of treatment, sperm density and motility had decreased markedly. After 2 months, sperm density dropped to 24% of normal, and only 12% of sperm were motile. Again, even the sperm capable of swimming were non-progressive. Study participants reported no changes in libido, and all hormonal, blood, and immune system tests were normal. Treatment lasted for 4-6 months. Two months after treatment stopped, sperm count and motility were back to pretreatment levels for all the men (Qian 1989).
Triptolide was one of the compounds identified as most promising by the World Health Organization collaborative research effort, and it “was selected for further toxicological and pharmacological evaluation” (Waites 1999). A team of researchers at Harbor-UCLA Medical Center undertook this evaluation. Based on their findings of incomplete recovery of fertility after long-term treatment, triptolide’s future as a contraceptive no longer looks so promising.
Short-term studies on rats showed that triptolide reduced sperm counts and resulted in almost zero motility. The researchers found no effect on reproductive hormones (Lue 1998). They also looked at the testes of treated rats at a molecular level, and found “little or no demonstrable detrimental effect” (Hikim 2000). Looking more closely at the sperm, they found that many were missing cell membranes, the DNA had become disorganized, and the mitochondria (cellular engines of movement) were damaged. The researchers concluded that triptolide was not affecting sperm as they were formed in the testes, but in the epididymis (a set of coiled tubes the sperm pass through) as they were maturing (Hikim 2000). However, the researchers noted that they could not rule out the possibility that triptolide did affect the testes somehow, because they had not treated the rats long enough to know with certainty.
A subsequent study of the longer-term effects of triptolide in rats did reveal an effect on the testes, although it was not consistent. After 12 weeks of treatment, the researchers found that the rats’ seminiferous tubules (the tubes where sperm are formed) showed varying degrees of cellular-level damage. When they stopped treatment after almost 12 weeks, only two thirds of the rats recovered fertility. The researchers concluded that the “possibility that an optimum dosing, which could induce infertility without causing any visible impairment of spermatogenesis and may promote a better rate of recovery, remains speculative” (Huynh 2000).
Tripchlorolide is another of the compounds identified by the World Health Organization collaborative research effort, and it is 200 times more potent than GTW. Studies in rats show that it has few side effects at the contraceptive dose, with no effect on hormones, libido, or immune system function (Lu 1990a, Wang 1999). Rats treated with tripchlorolide for 7 weeks showed “minimal testicular change but prominent epididymal spermatozoa damage” (Ye 1994).
A subsequent study showed that a daily dose of 50 micrograms of tripchlorolide per kilo of body weight was an effective contraceptive after 5 weeks of administration. Rats treated with this dose showed hallmark Tripterygium symptoms: a reduced sperm count and with the remaining sperm non-motile. Because “preliminary evaluation showed that the toxicity of tripchlorolide was much less than that of triptolide,” researchers hope that this compound will have more promising long-term results (Wang 1999, Yu 1992).
Tripdiolide, triptolidenol, 16-hydroxytriplide and T7/19
These four T. wilfordii extracts, which have known contraceptive effect, have yet to be systematically studied.
- Bai, JP, and YL Shi (2002) “Inhibition of Ca2+ channels in mouse spermatogenic cells by male antifertility compounds from Tripterygium wilfordii Hook. f.” Contraception 65(6): 441-5.
- Hikim, AP, YH Lue, C Wang, V Reutrakul, R Sangsuwan and RS Swerdloff (2000) “Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure.” Journal of Andrology 21(3): 431-7.
- Huynh, PN, AP Hikim, C Wang, K Stefonovic, YH Lue, A Leung, V Atienza, S Baravarian, V Reutrakul and RS Swerdloff (2000) “Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats.” Journal of Andrology 21(5): 689-99.
- Lou, D, and W Xu (1990) “Immunoregulatory effects of monomer T4 from Tripterygium wilfordii hook. I. Immunoregulatory effects of T4 on NK activity of mouse splenocytes [English abstract]” Zhongguo Yi Xue Ke Xue Yuan Xue Bao 12(2): 115-20.
- Lu, Q (1990a) “Comparative studies on antifertility mechanism and toxicology of Tripterygium wilfordii monomer T4 and gossypol [English abstract].” Zhongguo Yi Xue Ke Xue Yuan Xue Bao 12(6): 440-4.
- Lu, QX (1990b) “Effect of glycosides of Tripterygium wilfordii Hook on the reproductive system and major organs of male rats [English abstract]” Zhongguo Yi Xue Ke Xue Yuan Xue Bao 12(3): 203-7.
- Lue Y, AP Sinha Hikim, C Wang, A Leung, S Baravarian, V Reutrakul, R Sangsawan, S Chaichana and RS Swerdloff (1998) “Triptolide: a potential male contraceptive.” Journal of Andrology 19(4): 479-86
- Qian, SZ, CQ Zhong and Y Xu (1986) “Effect of Tripterygium wilfordii Hook. f. on the fertility of rats.” Contraception 33(2): 105-10.
- Qian, SZ (1987) “Tripterygium wilfordii, a Chinese herb effective in male fertility regulation.” Contraception 36(3): 335-45.
- Qian, SZ, YZ Hu, SM Wang, Y Luo, AS Tang, SY Shu, JW Zhou and TY Rao (1988) “Effects of Tripterygium hypoglaucum (Levl.) Hutch on male fertility.” Advances in Contraception 4(4): 307-10.
- Qian, ZS, YZ Hu and JS Tong (1989) “Studies on the effect of Tripterygium wilfordii on the reproduction of men.” Chinese Journal of Andrology 3: 129-32.
- Waites, GMH (1999) “The contribution of Asian scientist to global research in andrology.” Asian Journal of Andrology (1):7-12.
- Wang, ZP, ZP Gu, L Cao, Y Xu, GD You, BY Mao and SZ Qian (1999) “Effects of tripchlorolide on the epididymides and testes of rats.” Asian Journal of Andrology 1: 121-125.
- Yu, DQ, DM Zhang, HB Wang and XT Liang (1992) “Structure modification of triptolide, a diterpenoid from Tripterygium wilfordii [English abstract].” Yao Xue Xue Bao [Acta Pharmaceutica Sinica] 1992; 27: 830-6.
- Ye, W, Y Den, Y Huang and S Xue (1994) “Antispermatogenic effect of Tripterygium wilfordii and tripchlorolide (T4) on rat gametogenesis and spermatozoa.” Chinese Medical Science Journal 9(2): 110-3.
- Zhen, QS, X Ye and ZJ Wei [sic] (1995) “Recent progress in research on Tripterygium: a male antifertility plant.” Contraception 51: 121-9.