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This topic was aroused by the article of Viagra May Cause Heart Attack Deaths in Younger Men with No Heart Problems. It said that there were 522 people died in standard Viagra dosages, most of them from cardiovascular causes.

Viagra acts by inhibiting cGMP specific phosphodiesterase type 5, an enzyme that regulates blood flow in the penis. At the time in improving the erectile function powerfully, it caused many deadly inverse effects, too. Such as, priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and increased intraocular pressure,sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations and photophobia. Visual changes include blurring of vision and a curious bluish tinge.

According to the point of view of Chinese medicine that the enhancement of sexual function must be based on the improvement of overall health condition physically and psychologically rather than directly stimulate the artery expansion of local sexual organ by artificial chemicals.

From the attitude to the treatment of impotence, we can understand the different affect of the philosophy between the Western medicine and Chinese medicine -- reductionism and holism. The root of deadly side effect of Viagra is from the philosophical approach, which viewing the process of sexual erection was as same as the process of a water pump supply. It ignored the physical and psychological factors.

The testosterone supplement therapy (TST) and the hormone replacement therapy (HRT) both can improve the life quality for elderly people by improving the aging-related degeneration of reproductive system. However, they have deadly inverse effects, too, [1][2].

Based on the holistic philosophical approach, Chinese drugs have wonderful therapeutic effect on restoring the aging-related sexual dysfunction with lesser negative effect. Here, I will introduce some of modern research results of Chinese drugs on the improvement of human sexual function.

2. The sexual function improvement for male

Chinese drugs can enhance the sexual function from many aspects. Such as, it can improve the secretion function of the endocrine system, increase the weight of reproductive organs, enhance the gonadal function, restore the damaged sexual organs, increase the sexual desire, improve the erectile function, etc.

2.1. The effect of Chinese drugs on the secretion function of the endocrine system

Some Chinese drugs can improve the secretion function of the endocrine system by improving the function of hypothalamus - pituitary – gonadal axis, adrenal axis and thymus axis, etc. Therefore, it take the effect of improving the sexual function indirectly.

2.2. Increase the weight of reproductive organs and enhance gonadal function

In hydrocortisone treated rat model, Epimedium decoction gavages can significantly improve the sick symptoms of rats, and significant increase the weight of prostate, uterus, adrenal, thymus, seminal vesicle, levator ani muscle and sponge ball muscle, increase the levels of the estradiol and the plasma testosterone. In vitro, Icariin can significantly promote the TS secrete of the Rat’s Leydig cells.

Male mice administered epimedium decoction can increase the content of plasma testosterone (TS), increase weight of the testicular and the levator ani muscle.

2.3. Restore the damaged sexual organs

In impotence mice model, Epimedium extract can improve the DNA synthesis, promote the protein synthesis, regulate the cell metabolism and increase the body weight.

Epimedium decoction can effectively repair the injury of the Rat’s Leydig cells and maintain the normal spermatogenic cycle of the testicular seminiferous tubules epithelial.

2.4. Improve the sexual desire

Epimedium extractum has androgen-like effect, can promote the secretion of dog semen. The hormone activity of Epimedium extracts injection 20-40mg was equal to 7.5 mg of testosterone. Epimedium polysaccharide can affect the endocrine function of pituitary and increase the level of sex hormones.

Epimedium can significantly increase the sex desire through increasing the secretion of semen, after the spermatophore was being filled, it will stimulate the sensory nerve, and indirectly cause the sexual excitement.

Icariin can directly stimulate the secretion of estradiol in cultured follicular granulosa cell. At higher concentrations can promote the secretion of corticosterone in adrenal cortex.

Wolfberry polysaccharides gavages of 10 mg / (kg BW ? d) for semi-castrated rats can significantly shorten the latency of penile erection and the latency of mating cross, increase the percentage of mating rats and enhance the vitality of sperm count.

2.5. Improve the erectile function by increasing the expression of nitric oxide synthase

After the treatment of Icariin the erectile function was significantly improved in the rats of erectile dysfunction. The improvement of the erectile function has the same trend to the increase of expression of eNOS (nitric oxide synthase). It showed that the effect of Icariin on the erectile function was through the restoration of eNOS expression.

Icariin can increase the concentration of cyclic guanosine monophosphate (cGMP) in corpus cavernosum with the dosagedependent. It prompts that the mechanism of Icariin on the penis’ erection was related with increasing the cGMP of cavernosum smooth muscle to enhance the relaxation of the corpus cavernosum smooth muscle.

2.6. Effect of Icariin on the mRNA and protein expression of NOS isoform in corpus cavernosum of castrated rats

Objective: To investigate the long-term effect and pharmacological mechanism of Icariin on erectile dysfunction (ED).

Methods: Establish the ED model by castrating rats, then randomly divided into 4 groups, gavages of different doses of icariin and placebo respectively for 3 months.

Results: In castrated rats, the serum free testosterone decreased (P<0.01), the expression of the nNOS, iNOS mRNA and the expression of protein of corpus cavernosum was lower than that of non-castrated group (P<0.01), and there was no eNOS expression. However, after the gavages of different doses icariin, the expression of nNOS, iNOS mRNA and the expression of protein increased than the placebo group (P<0.05). Serum free testosterone had no significant changes (P> 0.05).

Conclusion: Long-term orally administration of the Icariin can increase the expression of nNOS, iNOS mRNA and the expression of protein in rat’s corpus cavernosum. It demonstrated the long-term therapeutic effect of Icariin on erectile function.

2.7. Restore the sexual function for aged male

Chinese drugs can inhibit the decline of serum E2 and DHT and make them tend to increase for aged rats. Therefore, protect the decline of sexual function for aged animal. Chinese drugs can increase the receptor number of hypothalamic cytoplasmic E2 and nuclear DHT for aged rats to make them close to the level of youth rats. Thereby delay the aging of hypothalamus - pituitary - gonadal axis.

Chinese drugs compound can resist the aging degeneration of all levels spermatogenic cells in testicular convoluted seminiferous tubules for aged male mice, and made the cell subsets microstructure was similar to that of youth and the lipofuscin level was not increase.

2.8. Resist the injury of chronic psychological stress on male sexual function

Studies have shown that the psychological stress is the common incentive for reproductive endocrine system diseases (RESD) [1] [2]. And the psychological stressor is increasing. Such as, social competition, work pressure, family variation, especially ongoing financial crisis has exacerbated this trend. Therefore, the studies of the mechanism of psychological stress inducing the RESD and the seeking of safe and effective intervention approaches on enhancing our ability of resilience of stressor is more pressing and practical significance.

On this purpose, Chinese drugs have demonstrated good performance.

2.8.1. Regulatory role of Chinese drugs on reproductive system of stress animals

In high-dose exogenous glucocorticoid treated rats, the levels of CaM mRNA in hypothalamus and gonadal increased, the levels of CaM mRNA in pituitary was no significant changes. Total flavones of Epimedium can reduce the levels of CaM mRNA in hypothalamus and testis; but, there is no significant impact on pituitary.

2.8.2. Regulatory role on the dysfunction of neural reproductive endocrine under the stress

Infulence of regulating liver-qi and tonifying kidney recipes on hypothalamus-pituitary-ovary axis in rats under psychologic stress

Methods: By rat’s tail clamp anger method establish the psychological stress model.

Results: In model group, the level of the hypothalamic-pituitary NE was decreaed, the level of the DA, 5-HT and 5-HIAA were increased. The levels of serum FSH, LH, E2 and P were declined, and the levels of the NE, DA, 5-HT, 5-HIAA and T were increased (P<0.05, P<0.01).

In Chinese drugs compounds group, the levels of rat’s serum P and LH were significantly higher than that of stress group, and the levels of the hypothalamic-pituitary NE and serum FSH, E2 were increased, the levels of the hypothalamic-pituitary DA、5-HT、5-HIAA and the serum NE、5- HT and T were decreased. Chinese drugs can inhibit the decline of the hypothalamic pituitary NE and the serum FSH, P, also inhibit the increase of the levels of the 5-HT, NE and T in hypothalamic pituitary and serum (P<0.05).

Conclusions: Chinese drugs can regulate the dysfunction of neural reproductive endocrine under the stress.

2.8.3. Effects of lycium barbarum polysaccharides (LBP) on Reproductive System in Rats with Chronic Psychologic Stress

Methods: 36 adult SD male rats, weighing 180-220 g, divide into 6 groups randomly. ① Saline group.② Stress group. ③LBP low dose group (gavages of 10 mg/kg). ④ LBP high dose group (gavages 20 mg/kg). ⑤ LBP low dose + Stress group (gavages of 10 mg/kg). ⑥ LBP high dose＋Stress group (gavages 20 mg/kg). All groups were administrated for 21 days.

The stress rat’s model was established by placing the rats into the bound boxes. Consecutively bound 5 h daily followed by exposure to 65 dB noises 1 h for 21 days.

Chinese drugs: 63% content of Lycium barbarum polysaccharides.

Results: Model rats: In the early stage, for the rats in stress group were easily angered, easily frightened, often was in high degree of alert state. With the extend of the stress time, the food intake was significantly decreased, weight was lost, fur color was matt dull, and conduct activities decreased. Depression-like performance emerged.

Body weight: The weight gain significantly reduced for stress rats with the statistical significant difference (P<0.05). Compared with the stress group, in LBP low dose, high dose and high dose + stress groups, the rat’s weight gain markedly increased with the statistical significant differences (P<0.05 or P<0.01). In LBP low dose + stress group, the rat’s weight gain increased, but no statistical significance in differences (P>0.05).

Testis and epididymis: In LBP high dose group, the weight gain of rat’s testis significantly increased (P<0.05) than those of saline group and stress group. Compared the weight gain of the rat’s epididymis between the each groups, there was no statistical significant differences (P>0.05).

Sperm parameters: In stress group, the number of the rat’s sperm decreased, the rate of live sperm decreased, the rate of sperm deformity increased, compared with the saline group, the differences are statistical significant (P<0.01). Compared with the stress group, in LBP high dose + stress and LBP low dose + stress groups, the number of the rat’s sperm significantly increased, the rate of the live sperm increased, the rate of sperm deformity decreased, there are statistical significance in differences (P<0.01 or P<0.05).

Serum testosterone: Compared with the saline group, in the stress group, the level of the rat’s serum testosterone significantly decreased (P<0.05). Compared with the stress group, in LBP low dose, LBP high dose, LBP low dose + stress, LBP high dose + stress groups, the level of the rat’s serum testosterone significantly increased (P<0.05 or P<0.01).

Pathological patterns of the testicular tissue: In the saline group, LBP high does group and LBP low dose group, the rat’s testis seminiferous tubules ranged neatly, from the basement membrane to the cavity surface, sequentially can see the visible spermatogonia, spermatocyte and sperm cell that ranged compactly and neatly. A large number of matured sperm can be seen in the cavity. In stress group, the testis tissue of rats, the amount of the seminiferous tubules, the layers of the spermatogenic cells and the number of spermatogenic cells at all levels apparently reduced. The spermatogenic cells ranged areosis disorders and the amount of matured sperm cells in cavity apparently decreased. In the LBP high dose + stress group, the pattern of the rat’s testis tissue was similar to the normal one. In the rat’s testis tissue of the LBP low dose + stress group, the seminiferous tubule partially degenerated, the number of spermatogenic cells decreased with areosis disorders ranged, and the amount of matured sperm cells in cavity decreased.

Conclusion: Lycium barbarum polysaccharides can enhance the reproductive function of chronic mentally stress rats. The mechanism might be through the regulation of the hypothalamus-pituitary-gonadal axis and the target receptors.

Discussion: From the study we can understand that the psychological stress has powerful damage effect on reproductive function. Chinese drugs have protective effect on the reproductive function.

2.9. Effects of Chinese drugs on exercise-induced low serum testosterone

Effects of Chinese Herbal Preparation for Invigorating Kidney on Function of Hypothalamic - Pituitary - Gonad Axis in Rats

Objective：To observe the regulatory effect of epimeddium, broomrape and wolfberry on low serum testosterone and hypothalamus - pituitary - gonadal axis (HPG) function for heavy load long-term swimming rats.

Method: By rat’s load swimming (the load increased by degrees) establishes low blood testosterone models and divided into swimming group and swimming + Chinese drugs groups.

Results: After 6 weeks swimming fatigue, in swimming group, the levels of the rat’s blood testosterone decreased significantly, the corticosterone increased significantly, the ratio of testosterone with corticosterone dropped by 71%. The dysfunction and even failure have emerged in the morphological changes in the cell ultra-structure of the hypothalamic GnRH neurosecretory cells, pituitary LH, FSH promote gonadal cells and testes leydigscells in the rat’s hypothalamus - pituitary - gonadal axis.

In swimming + Chinese drugs group, the levels of the rats’ blood testosterone significantly increased than that of swimming group. And the morphological changes demonstrated the improvement at all levels cells’ ultra-structure of hypothalamus - pituitary - gonadal axis.

Conclusions: Regulatory hypofunction of hypothalamus - pituitary - gonadal axis is the important reason for exercise induced rats’ low blood testosterone. Chinese drugs can significantly improve the exercise induced low blood testosterone by regulating the function of hypothalamus - pituitary - gonadal axis and maintaining the integrity of the cell ultrastructure in gonadal axis.

2.10. Effects of Chinese drugs on partial androgen deficiency of elderly

The testosterone supplement therapy (TST) can significantly improve the symptoms of partial androgen deficiency in the aged male (PADAM). But there is safety issue. Such as, induce the erythrocytosis, impair the liver function. Moreover, also there are potentially dangerous of prostate and cardiovascular diseases. In addition, a study showed that injection of testosterone propionate in rabbit muscle can increase the level of serum testosterone, however, once the drug is withdrawal, the testosterone levels will be decreased in lower than the normal levels, which emerged the phenomenon of negative feedback. Those facts showed that the TST has shortcomings.

2.10.1. The protective effects of extracts of Icariin and Dodder seed on the reproductive function of the rats with partial androgen deficiency

　　ZHANG ZhenBao，YANG QingTao，YANG JingQiu,et al

　　Department of Urology，the Second Affiliated Hospital，Shantou University Medical College，Shantou 515041，Guangdong，China

　　【Abstract】 Objective To evaluate the protective effects on reproduction of Icariin(ICA) and semen cuscutae(SSC) on partial androgen deficiency(PAD) ratsMethods The male rat model for impaired reproduction system and partial androgen deficiency were made by cyclophosphamide to determine the content of serum testosterone，luteinizing hormone(LH) and folliclestimulating hormone(FSH) after igICA and SCCThe change of histology of the testis and the penis were observed by microscope with the method of HE staining and TUNEL method respectivelyResults ①The contents of serum testosterone in ICA group were statistically higher than that in control group and model group，and were statistically lower than that in testosterone group (P＜005)However，contents of serum testosterone in SSC group were higher than that in model group，and lower than that in testosterone groupBut there had no statistically difference between SSC group and control group②There had no statistically difference among every group as to the contents of LH and FSH③The cell apoptosis rate in rat penis in testosterone group and ICA group were statistically lower than that in model group(P＜005)But there had no statisticaldifference between SSC group and model groupConclusions ICA and SSC both have the protective effects on reproduction on partial androgen deficiency rats，but ICA is much more beneficial to PAD in the aging male(PADAM)

Objective: To evaluate the protective effects of Icariin (ICA) and Dodder seeds (DS) on the reproductive function of partial androgen deficiency (PAD) to explore the alternative approaches for TST in Chinese drugs.

Methods: 60 SD 15-month-old male rats were divided into 5 groups: blank group, model group, Icariin group, Dodder group, testosterone group, 12 in each group. The partial androgen deficiency (PAD) model was established by drug castration with the reproductive toxicity of cyclophosphamide.

Besides the blank group, the other 4 groups were given intraperitoneal injection of cyclophosphamide (20 mg ? kg-1 ? d-1) for 5d. Then, the model group was no longer given any medication. Icariin group was gavages 40% single Icariin-glucoside for 200 mg ? kg-1 ? d-1; Dodder group was gavages dodder extract of (8:1) 200 mg ? kg-1 ? d-1, and the testosterone group was subcutaneous injection of testosterone propionate 5 mg?d-1. All was administrated once daily for 7 days.

Results: Compared with the blank group, rats in model group, the weight was lost, the activity reduced, the hair was curly, matte and dull yellow, the testosterone levels declined (P<0.05), bone synthesis reduced but absorption increased and the weight of testes and seminal vesicle reduced. Biopsy showed that the diameter of the testicular seminiferous tubule narrowed, the spacing widened, the seminiferous epithelial thinned, the connective tissue was hyperplasia, the apoptosis of the spermatogenic cells and mesenchymal cells increased, the apoptosis of smooth muscle cells of corpus cavernosum increased and the degenerative changes emerged.

Weight of body: The weight of rats in Icariin group, Dodder group and testosterone group were higher than the model group’s but lower than the blank group’s, and the Icariin group’s and Dodder group’s was lower than the testosterone group’s (P<0.05).

The weight of testis, epididymis, seminal vesicle: Compared with the model group, the weight of rat’s testis in all group was increased (P<0.05). But the weight of rats’ epididymis was no obvious increase. The weight of rats’ seminal vesicle in Icariin group were higher than the model group’s but lower than the testosterone group’s (P<0.05). The weight of rats’ seminal vesicle in Dodder group were lower than the blank group’s and the testosterone group’s, no significant difference with the model group’s (P<0.05).

Serum reproductive hormone: For the levels of rats’ serum testosterone: Icariin group’s was significantly higher than the blank group’s and model group’s, but lower than the testosterone group’s (P<0.05), Dodder group’s was significantly higher than the model group’s but lower than the testosterone group’s (P<0.05), has no significant differences with the blank group’s. The levels of the serum LH, FSH were no significant difference in each group.

The apoptosis: Apoptotic cells in each group have emerged. The results were as following. Icariin group’s was (34.26% ± 3.45%) and the testosterone group’s was (22.65% ± 5.17%), the two groups’ apoptosis rate were lower than the model group’s (48.28% ± 6.74%), there was a statistical significant difference (P<0.05). Dodder group’s (41.98% ± 8.12%) were no statistical significant difference with the model group and the blank control group (39.68% ± 6.02%).

Conclusions: Icariin and Dodder both have the protective effects on reproductive function of partial androgen deficiency rats，but Icariin is much more beneficial to the PAD in the aged male rats.

Discussion: The Epimedium and Cuscuta are the main drugs that were used for treating male climacteric syndrome in Chinese medicine clinically.

In this experiment, Dodder Seed extract can significantly increase the concentration of the serum testosterone, and increase the weight of rat body and genital testicular. Icariin can make the testosterone concentration higher than the model group, even higher than the blank group, can inhibit the reduction of seminal vesicle weight and the increase of the apoptosis of smooth muscle cell of corpus cavernosum induced by cyclophosphamide.

Epimedium and Cuscuta can increase the diameter of testicular seminiferous tubule, increased the intensive of the seminiferous tubule, increase the spermatogenic cells and interstitial cell. It showed that Epimedium and Cuscuta can slow down the degenerative changes of testicular tissues with androgen-like or androgenic promotion-like effect. They can fight against PAD, but the effect was more moderate, weaker than that of testosterone propionate.

Icariin and Dodder Seed are pure traditional Chinese drugs. The price is lower, the effect is moderate with low toxicity, suitable for long-term use, has the potential to become an ideal treatment drugs for PADAM.

Opinion derived from above paper: If the Icariin and Dodder was used in integrating or used in integrating with testosterone will be gotten much better results from their potentiating synergistic effects. The dosage and the side effect of the testosterone would be decreased largely.

2.11. Male infertility

The United States does have infertility rate-17 percent, and this rate continues going up. However, China has the lowest infertility rate, less that 3 percent. The lower infertility rate was contributed from the natural Chinese drugs rather than the difference of the ethnic origin. Because that the reproductive function is an important part of the sexual function, which can not be separated from. Chinese drugs will naturally improve the reproductive function at the time in improving the sexual function.

Here, I will introduce the wonderful therapeutic effect of Chinese drugs on male infertility by clinical cases.

2.11.1 Sperm generation capsule treats 1645 cases of male infertility

Cases selection: 1645 cases of male infertility, among them, 21 - 30-year-old was 584 cases (35.50%), 31 - 40-year-old was 1036 cases (62.98%), over 40-year-old was 25 cases (1.52%). The infertile course was 1.5 - 14 years. They are no congenital hypoplasia, no bilateral cryptorchidism, no bilateral epididymal tuberculosis, normal in vas deferens and normal in sexual function. The gynecological examinations showed that their spouse did not suffer any diseases that affect the reproductive.

Drugs: Sperm generation capsule was made of compound Chinese drugs. Each capsule was equivalent to the crude drug of 4.54g. 5 capsule x 3 times daily with an empty stomach, 3 months for a course of treatment.

Standard of efficacy: (1) Recovery: The spouse had been pregnant; (2) Marked effective: Semen examination resumed to normal; (3) Effective: Semen examination resumed to normal partially; (4) Ineffective: After 3 months treatment, the semen examination was no obvious change.

Results: Recovery was 971 cases (59.03%); marked effect was 385 cases (23.40%); effective was 231 cases (14.04%); ineffective was 58 cases (3.53%). The total effective rate was 96.47%. In the treatment of courses, the shortest one was 24 days, the longest one was 180 days and the average was 56 days.

The reasons of ineffective were that those patients’ sperm density was less than 1 million / ml or suffering the sperm immobility syndrome.

Conclusion: The sperm generation capsule can enhance the gonadal function by increasing the number of sperm, enhancing the motility of sperm, reducing the occurrence of abnormal sperm and improving the liquefaction time.

3. The sexual function improvement for female

The main Chinese drugs on the enhancement of sexual function for female are similar to those for male. This is because that the treatment of sexual function in Chinese medicine is focusing on the improvement of the overall health condition rather than that of the Viagra focused on the sexual organ only.

3.1. The improvement of female sexual arousal dysfunction

Chinese drugs can enhance the female sexual arousal ability and sexual pleasure by improving the relaxation of corpus cavernosum clitoridis and vaginal smooth muscle. The increased relaxation will help to increase the blood flow velocity and volume in clitoris and vagina to enhance their sexual sensitivity.

3.1.1. Effect of Icariin on the NO-cGMP pathway in clitoris erection

Methods: In vivo, vitro tested the nitric oxide synthase (NOS) and the expression of phosphodiesterase type 5 (PDE5) in the corpus cavernosum clitoridis. By SNP stimulating observed the effect of Icariin on the levels of cGMP. By primary cultured smooth muscle cells of rabbit’s clitoral corpus cavernosum observed the activity of NO and NOS. By the model of ovariectomized rat’s sexual dysfunction and the Laser Doppler Technology observed the hemodynamic changes on vaginal wall. After placebo-control oral administration in 5mg/kg/day for 4 weeks observed the long-term effects of Icariin.

Results: There were NOS and PDE5 expression in the tissues of corpus cavernosum clitoridis. Icariin markedly increased the concentration of cGMP and the activity of NO and NOS in smooth muscle of corpus cavernosum clitoridis with the dose-dependent.

In sexual dysfunction model group, blood flow velocity and the area under the curve of vaginal wall were significantly decreased than the normal control group, and the smooth muscle of vaginal wall was significantly decreased. After 4 weeks of Icariin oral administration, the blood flow velocity and the area under the curve of vaginal wall was significantly increased than the normal control group, and smooth muscle of vaginal wall was increased.

Conclusion: Icariin can enhance the female sexual function by regulating the NO-cGMP pathway.

Discussion：Icariin can regulate the expression of the NOS and PDE5 and the NO-cGMP signaling pathway in corpus cavernosum clitoridis and vaginal smooth muscle. Through increasing the content of NO and cGMP enhance the relaxation of corpus cavernosum clitoridis and vaginal smooth muscle. The increased relaxation will help to increase the blood flow velocity and volume in clitoris and vagina. Thereby enhance the female sexual arousal ability.

Until after 4 weeks of Icariin gavages, the velocity and the volume of the blood flow of vaginal wall were significantly increased, and the smooth muscle was increased. The results indicated that Chinese drugs need some times to take the better effect because that enhanced sexual function was the natural result with the overall health condition was being improved gradually. So that even if the cessation of medication, the enhanced sexual function will exist continuously.

3.1.2. Effects of Icariin on NO production and NOS activity of rabbit clitoral corporal smooth muscle cells

Objective: investigate the effects of the Icariin on production of Nitric Oxide (NO) and activity of Nitric Oxide Synthase (NOS) of smooth muscle cells in rabbit’s corpus cavernosum clitoridis.

Methods: By enzyme digestion method in vitro culture the smooth muscle cells of rabbit’s corpus cavernosum clitoridis.

Results: Cultured tissue showed typical morphological characteristics of the smooth muscle cells. The Icariin can increase the activity of NOS and the generation of NO (P<0.01) in smooth muscle cells of rabbit clitoral corpus cavernosum with the concentration dependent.

Conclusion: Icariin can increase the generation of NO of smooth muscle cells of corpus cavernosum clitoridis by enhancing the NOS activity。Those increased NO will enhance the relaxation of the smooth muscle under the sexual stimulating to enhance the swollen erectile function of the clitoris.

3.2. Effects of Chinese drugs on Pituitary-gonadal Axis in female rats

3.2.1. The effects of Icariin on Pituitary-gonadal Axis in female rats

Methods: 4-month-old female rats model, studied the effect of Icariin on the reproductive hormones: FSH, LH and E_2 in the serum of female rats, observed the effect of Icariin on the development of ovarian and uterine organs . By primary cultured pituitary cells and semi-quantitative RT-PCR studied the effect of Icariin on the expression of FSH mRNA and LH mRNA of the Rat’s pituitary cells.

Results: Certain doses of Icariin can increase the secretion of the reproductive hormones: FSH, LH and E_2 of female rat’s serum. And promote the development of Rat’s follicle. However, for the development of uterine was no obvious impact. Icariin can promote the secretion of FSH and LH of anterior pituitary cells and increase the expression of FSH mRNA and LH mRNA of pituitary cells with dose selection.

Conclusion: Icariin can increase the secretion of the reproductive hormones: FSH, LH and E_2 of female rat’s serum, and increase the expression of FSH mRNA and LH mRNA of pituitary cells. Icariin can promote the development of rat’s follicle, no obvious impact on the development of uterine.

3.3. Research review of the therapeutic mechanism of compound Chinese drugs on the Hypothalamus-pituitary- ovarian Axis

Abstract: Review the research results of the therapeutic mechanism of compound Chinese drugs (CCD) on the Hypothalamus-pituitary- ovarian Axis in recent years. Compound Chinese drugs can regulate the disordered function of autonomic nerve, reproductive endocrine system and immune system, thereby to take the bidirectional regulatory effect for female’s neuro-endocrine -immune system.

Animal models selection: Early age animals, elderly age animals, ovariectomized animals and sterilized animals by gavages of androgen, etc.

Results: The effects of CCD on sex hormones

① CCD can bidirectional regulate the level of sex hormones, increase the level of the sex hormone receptor, increase the levels of the endometrial PR, ER in ovariectomized rats and promote the growth of the uterine.

② CCD can significantly increase the levels of the serum E2, P, and the index of uterus and ovarian for the young female rats.

③ CCD can increase the serum E2, P, decrease the serum FSH, LH for the ovariectomized rats.

④ CCD can increase the serum E2、FSH、LH and decrease the GnRH in hypothalamus and plasma for the 18-month-old rats.

The effect of CCD on the histomorphology of gonadal axis

① The adenohypophysis’ structure is clear, the sinusoid increased, the gland cells is dense, the cytoplasm is full, the nuclei is round and large, and the nucleoli is clear.

② In polycystic ovary mice model, increase in uterine weight, interstitial cells of polycystic ovary is hypertrophy and the ovarian weight increased.

③ In androgen sterilized rat induced by androgen, the ovarian weight increased, the corpus luteum increased, the ovarian granulosa layer increased. There are eggs in dominant follicle, the interstitial gland significantly increased.

④ The adrenal cortical zona reticularis thinned, the lipid droplets increased.

The effect of CCD on the neuroendocrine network

① CCD can partially improve the endocrine disorders of the menopause rats by reducing the level of the NE, DA of hypothalamus and NE, E2 of plasma.

② CCD can regulate the activity of NO, NOS and the content of nNOS, mRNA in hypothalamus, in some extent can inhibit the hormone NOS / cGMP system by affecting the nNOS transcription.

③ CCD can cure the idiopathic precocious puberty.

④ CCD can regulate the synthesis and release of growth hormone and the expression of hypothalamic protein and periventricular nucleus SS gene by regulating the hypothalamus somatostatin, gene expression and protein expression.

⑤ CCD can increase the level of declined hypothalamic NE of ovariectomized female rats, reduce the abnormal increase of 5-HT and 5-HIAA, so that make the ratio of 5-HT / NE close to normal. These indicate that Chinese drugs can improve the disorder of the monoamine central neurotransmitters of the menopausal rats. At the same time can increase the activity of IL-2, therefore can regulate the immune function of cells and humoral.

3.4. Restore the sexual function for aged female

The histochemical examination within the genital showed that Chinese drugs can improve the ovarian function, delay the aging process of uterine and ovarian. Such as, make the uterine hypertrophy or normal, uterine epithelial AKP positive, and produce the corpus luteum and follicle in ovarian.

3.4.1. The clinical observation of climacteric syndrome treated with Yikunning

Objective: Observation of clinical efficacy of Yikunning (A compound Chinese drugs) on perimenopausal syndrome.

Methods: 44 patients with perimenopausal syndrome were randomly divided into Yikunning group and Livial group. Two groups continuously administrated for 3 months. Then the menopausal symptoms were estimated by kupper-man score method. The levels of the serum hormone were determined by RIA method before and after treatment.

Results: The effect of the Yikunning on improving the perimenopausal symptoms was better than the Livial, there was a statistical significance. The effect of Yikunning on improving the hormone levels was similar to the Livial, there was no significant statistical difference.

Conclusions: The effect of Yikunning on improving the perimenopausal symptoms is better than the Livial and on regulating the endocrine is similar to the Livial. However, Yikunning has the advantages of therapeutic effect lasting longer and side effects lesser.

Discussion: Livial is a synthetic steroid hormones used for hormone replacement therapy (HRT). It mimics the activity of the female sex hormones oestrogen, progesterone and androgen testosterone for aged female. It has positive therapeutic effect clinically.

As same as other synthetic drugs, Livial has terrible side effects, too. Such as, increased risk of breast cancer; increased risk of stroke and of blood clots forming in the veins; some breakthrough bleeding or spotting in the first few months of taking this medicine; missing a dose may increase the chance of bleeding or spotting; stabbing pains or swelling in one leg; pain on breathing or coughing; coughing up blood; breathlessness; sudden chest pain; sudden numbness affecting one side or part of the body; fainting; worsening of epilepsy; migraine or severe headaches; visual disturbances; severe abdominal complaints; increased blood pressure; itching of the whole body; yellowing of the skin or eyes (jaundice); severe depression.

However, Yikunning is a pure natural compound Chinese drugs, it take the effect by restoring the function in secreting sex hormones for aged female organs. Therefore, its side effect is lesser and the therapeutic effect is longer.

3.4.2. Effect of Climacteric Happiness on Perimenopausal Rat’s Hormone

Climacteric Happiness (CH) is a compound Chinese drugs made from the experience formula for treating perimenopausal syndromes. After years of clinical applications and observations, the therapeutic effect was proved. This study is from the endocrine level to investigate the mechanisms of the therapeutic effect.

Methods: 50 female 12~15-month-old SD rats were randomly divided into 5 groups: CH high dose group, CH medium dose group and CH low dose group, blank group and Nylestriol group. 10 adult non-pregnant 4~5-month-old female rats set as normal group.

Rats in 3 CH groups were 3mL CH gavages, which containing crude drugs respectively：7.4g、3.7g and 1.85g, rats in blank group were 3mL saline gavages and rats in normal group were 4mL saline gavages, all group administrated once daily for 30 days. Nilestriol group was 0.036mg Nylestriol gavages, once every 2 weeks for 30 days.

Results: In all CH groups, the level of rat’s serum E2 was significantly higher than the blank group (P<0.05). Compared with normal group, the level of rat’s serum E2 of high dose CH group has no significant difference (P>0.05). The determination results were as following table.

Table: Determination Results of Rat’s Serum E2, FSH and LH for Each group

Groups	E2 (pg/mL)	FSH (mIU/mL)	LH (mIU/mL)
CH High dose	14.00±2.42**△	6.89±1.43*	10.80±1.36**
CH Midium dose	9.29±4.44**△△	7.52±2.56	10.90±1.60*
CH Low dose	7.88±3.41* △△	8.27±2.25	11.20±2.70
Normal Group	16.80±5.27** △	6.47±1.19*	10.50±1.88*
Blank Group	4.57±2.72 △△	8.32±1.60	12.80±1.39
Nylestriol Group	17.40±5.55**	6.24±1.35*	10.30±2.15*

Note: Compared with the blank group: *P<0.05, **P<0.01; Compared with the Nylestriol group: △P>0.05, △△P>0.01

Conclusions: Climacteric Happiness can increase the serum E2 level and decrease the serum FSH, LH levels of perimenopausal rats

3.5. Resist the injury of chronic psychological stress on female reproductive function

Psychological stress can activate the hypothalamus - pituitary - adrenal axis, and impact the function of female reproductive endocrine from the levels of hypothalamus, pituitary and ovarian. Chinese drugs can take the anti-chronic psychological stress effect by improving the female reproductive endocrine function.

3.5.1. Effect of repeated immobilization stress on ovarian function in female rats

Method: Sexual matured female rats were given immobilization stress once daily for 15 d. Observe the sexual periodic change by vaginal smearing. At the same time to observe the changes of the level of the plasma estradiol and progesterone.

Results: Repeated stress can cause the female rat’s ovarian dysfunction. The sexual cycle extended or no physical laws or sustained in diestrum without asexual cycle alternating. The secretion function of ovarian estradiol was hypofunction; the secretion function of progesterone was obvious disorder. The plasma estradiol levels were significantly reduced in various stages of sexual cycle and / or menstrual cycles was disorders or disappears. The progesterone level was significantly increased and the physiological secretion pattern was disorder. The plasma progesterone levels of some rats changed toward that of climacteric rats.

Conclusion: Stress can induce the ovarian dysfunction and degradation.

3.5.2. Effects of flavonoids from Cuscuta chinensis on ovarian endocrine in female rats exposed to psychologic stress

Objective: Observation of the regulatory role of Cuscuta flavonoids on the decline of ovarian endocrine function caused by psychological stress.

Methods: Established rat’s ovarian endocrine dysfunction model by composite stress of sound - Light – electricity stimulating.

Results: For stress rats, the Cuscuta flavonoids can significantly increase the levels of serum E2, P and the weights of pituitary, ovarian and uterine. But there was no significant impact on the level of adrenal ascorbic acid.

Conclusion: The Cuscuta flavonoids can significantly improve the ovarian endocrine function of psychological stress rats.

3.5.3. Effects of Flavonoids from Semen Cusseta on Changes of β-EP in Hypothalamuses and FSH and LH in Anterior Pituitaries in Female Rats Exposed to Psychological Stress

Objective: Study the regulatory mechanism of Cuscuta flavonoids on the ovarian endocrine function of stress rats.

Methods: Established rat’s ovarian endocrine dysfunction model by composite stress of sound - Light – electricity stimulating.

Results: The hypothalamic β-EP levels of psychological stress rats were significantly increased. Cuscuta flavonoids can markedly reduce the level of hypothalamic β-EP, increase the number of pituitary basophilic cells and the level of pituitary LH. But there was no significant impact on the level of pituitary FSH.

Conclusion: Cuscuta flavonoids can significantly improve the ovarian endocrine function by reducing the level of hypothalamic β-EP and increasing the level of pituitary LH for psychological stress rats.

3.5.4. Effects of Chinese drugs on hypothalamus-pituitary-ovary axis in hanging stress female mice

Original name was Effect of Liuwei Dihuang Decoction on Hypothalamus-pituitary-ovary Axis in Hanging Stress-loaded Female Mice

Objective: Observation of the changes of hypothalamus - pituitary - ovarian (HP0)-axis function in hanging stress female mice and the effect of Liu Wei Di Huang Tang (LW), a compound Chinese drug.

Methods: By hanging stress method establish HPO axis dysfunction model in female rats, in the first 1 – 3 d hanging 30min, then increase 30min by every 3d. No total hanging days were mentioned.

Results: The weight of stress mice reduced, the estrous cycle and the estrus interval prolonged. The level of hypothalamus CnRH and pituitary LH declined, the concentration of serum estradiol increased. Oral LW has no significant effect on estrous cycle of stress mice, but can reduce the weight lost. Oral LW can significantly improve the levels of the hypothalamic GnRH and pituitary LH and significantly reduce the concentration of serum estradiol.

Conclusion: Hanging stress can induce the dysfunction of rat’s MPO axis. LW has regulatory effect on dysfunction of rat’s MPO axis.

3.6. Female infertility

May 11, 2009, The Herald-Mail reported that Area moms say acupuncture helped them to conceive in Hagerstown city, Maryland State, USA.

“Kelly Morton, 37, of Hagerstown says she and husband Jason wanted to give their daughter Meredith, 6, a sibling.”

“But after nearly three years of trying to get pregnant and suffering through several miscarriages, Morton says she turned to two intrauterine insemination (IUI) procedures as well as an in vitro fertilization (IVF) procedure.”

“All three were unsuccessful, leaving Morton physically and emotionally spent, and she and her husband still without another child.”

““It was devastating,” she says.”

However, finally she succeeds happily with the help of acupuncture and Chinese herbs.

Kelly Morton holds daughter Sadie, 8 weeks, in front the wall of children who have been conceived using Chinese medicine. Sadie was conceived with the help of acupuncture and Chinese herbs.

Many others have the same experiences.

Above cases are sufficient to demonstrate the magic therapeutic effect of Chinese medicine on female reproduction.