Keywords
TCM moxibustion - ovarian damage - heat-sensitive moxibustion - electroacupuncture
Introduction
In the female reproductive system, ovaries play a vital role. However, ovarian injury
often brings great trouble to the female and health threat. Clinically, diminished
ovarian reserve (DOR), polycystic ovary syndrome (PCOS), premature ovarian failure
(POF), and premature ovarian insufficiency (POI) are relatively common ovarian injury
problems. Studies have shown that increase in the incidence of DOR has affected approximately
10% of women causing infertility.[1] And the prevalence of PCOS in women of reproductive age is as high as 15%.[2] Therefore, approximately 1 to 3% of adult women worldwide are diagnosed with POF.[3] All of these diseases can damage the ovaries. Traditional Chinese medicine (TCM)
moxibustion, as a natural therapy with a long history, is a unique health resource
in China. It plays an important role in moxibustion therapy, and its application in
the treatment of ovarian injury has gradually attracted people's attention.[4]
Some literature research shows that TCM moxibustion has significant effects on improving
ovarian function,[5] increasing ovulation rate and pregnancy rate,[6] and regulating endocrine level.[6]
[7] This review will comprehensively analyze the types of common moxibustion methods,
the intervention period of moxibustion and the types of ovarian injury, covering the
relevant literature in the field of clinical efficacy and experimental research of
TCM moxibustion on ovarian injury in recent years, and explore the efficacy and potential
mechanism of TCM moxibustion in the treatment of ovarian injury. In addition, we will
also pay attention to the comparative research on the efficacy and safety of TCM moxibustion
and other treatment methods, such as Western medicine, Chinese medicine, and combination
drugs, to provide more basis for clinical practice.
Clinical Study on the Application of Moxibustion Therapy in Ovarian Injury
Clinical Study on the Application of Moxibustion Therapy in Ovarian Injury
Acupuncture
Acupuncture is a unique means of treating diseases in China. In recent years, acupuncture,
as a treatment method of treating from the outside to the inside, plays an important
role in the treatment of ovarian injury.
Clinically, acupuncture has a significant effect in the treatment of PCOS.[8] Compared with conventional drug treatment, acupuncture in the treatment of PCOS
combined with infertility can significantly improve the total effective rate of clinical
treatment, ovulation rate, and pregnancy rate.[6] And there were also marked reductions in serum levels of luteinizing hormone (LH),
testosterone (T), and follicle-stimulating hormone (FSH).[9] For obese patients with PCOS, acupuncture can not only achieve ideal results but
also obtain high satisfaction.[10] In addition, acupuncture also has significant effects in the treatment of POF and
reduction of ovarian reserve function. Niu et al[7] founded that acupuncture could significantly reduce the serum levels of FSH and
LH, increase the level of antimullerian hormone (AMH), increase the number of basal
antral follicles, and increase the maximum ovarian plane diameter in patients with
decreased ovarian reserve. In the treatment of patients with decreased ovarian reserve
function with kidney deficiency and liver depression syndrome, Liang[11] showed that compared with the sequential treatment of estrogen and progesterone
cycles, acupuncture and moxibustion can also significantly increase the serum AMH
level, improve ovarian reserve function, and improve the clinical syndrome of TCM
in patients with kidney deficiency and liver depression syndrome. This is of great
significance for improving ovarian reserve function and preventing and delaying the
occurrence of POF.
Moxa-moxibustion
Moxa-moxibustion is a TCM therapy in which folium artemisiae argyi is used to make
moxibustion materials, where they burnt to generate heat and stimulate acupoints or
specific body surface areas, and thus, the goal of disease prevention and treatment
is achieved. Most studies have shown that moxibustion combined therapy can be used
to treat patients with ovarian injury.
Similar to acupuncture and moxibustion therapy, moxa-moxibustion can also be used
for patients with ovarian insufficiency such as PCOS, POF, and decreased ovarian reserve
function. For the treatment of patients with PCOS, moxa-moxibustion combined with
Western medicine and Chinese medicine can significantly improve the overall effective
rate, ovulation rate, and pregnancy rate than Western medicine or Chinese medicine
alone, and the regulation of hormone levels such as FSH, LH, and AMH is also significantly
improved than with single therapy alone.[12]
[13] This type of combination therapy also has a similar therapeutic effect on patients
with reduced ovarian reserve, which can improve ovarian function by increasing the
total response rate and maintaining the stability of sex hormones such as FSH and
estradiol (E2), thus improving ovarian function.[5]
[14] Wu and Shu[15] also showed that massotherapy and moxa-moxibustion combined with Yougui Pills can
significantly improve the efficacy of POF with the syndrome of spleen and kidney yang
deficiency, and its effect on regulating FSH, LH, and E2 levels has also been proved. At the same time, this therapy can also improve the
safety of treatment.
Heat-Sensitive Moxibustion
Heat-sensitive moxibustion is a new type of therapy developed on the basis of moxa-moxibustion,
which is to find heat-sensitive acupoints through suspension moxibustion and apply
specific techniques to stimulate moxibustion to achieve individualized desensitization
of acupoints, which can significantly improve the effect of moxibustion.[4] With the clinical application of thermosensitive moxibustion, the effectiveness
of this technology in treating ovarian injury has also been developed.
Li and Fan[16] showed that self-made Yiqi Huoxue decoction combined with heat-sensitive moxibustion
on the basis of conventional Western medicine could significantly improve the total
effective rate, ovulation rate, and pregnancy rate of PCOS patients and also improve
the serum sex hormone levels of patients. For PCOS patients with the syndrome of kidney
yang deficiency, heat-sensitive moxibustion combined with letrozole can significantly
improve follicular development and endometrial thickness compared with letrozole alone.
Unlike the study conducted by Li and Fan 2019,[16] no significant advantage was found in improving pregnancy and ovulation rates with
this combination therapy,[17] which may be related to the type of combination or the type and severity of patients.
In the treatment of PCOS infertility patients, the therapeutic effect of acupuncture
combined with heat-sensitive moxibustion is significantly better than that of acupuncture
combined with mild-warm moxibustion. It can not only significantly improve the condition
of polycystic ovary, but also regulate the levels of LH and FSH, which is significantly
better than acupuncture combined with mild-warm moxibustion.[18] Similar to the above, heat-sensitive moxibustion can also be used to treat patients
with POF or POI. A study has shown that heat-sensitive moxibustion combined with Bushen
Shugan prescription has a higher clinical efficiency in the treatment of patients
with POI than Bushen Shugan prescription alone, and its regulation of hormone levels
and ovarian function is significantly better than Bushen Shugan prescription alone.[19] For patients with POF, electroacupuncture combined with heat-sensitive moxibustion
is more effective than taking Climen orally.[20] Under the same condition of taking Climen orally in the control group, the overall
efficacy of acupuncture combined with heat-sensitive moxibustion showed no significant
advantage, but it had fewer side effects and was more easily accepted by the patients.
Yang et al[21] showed that the effect of heat-sensitive moxibustion combined with artificial cycle
therapy in the treatment of POF with spleen–kidney yang deficiency syndrome was significantly
better than that of artificial cycle therapy and speculated that its efficacy may
be related to the improvement of serum prefibrin and vascular endothelial growth factor
levels. For the treatment of POF with kidney yin deficiency syndrome, heat-sensitive
moxibustion combined with meridian ebb acupoint application is not only superior to
single meridian ebb acupoint application but also has higher safety.[22]
Experimental Study on the Application of Moxibustion to Ovarian Injury
Experimental Study on the Application of Moxibustion to Ovarian Injury
Acupuncture
Studies have shown that acupuncture has a significant effect on regulating sex hormone
levels in PCOS rats, which can significantly reduce the levels of serum LH, FSH, T,
and AMH and significantly increase the level of E2.[23] And it can also improve the ovary morphology and function of PCOS model rats induced
by dehydroepiandrosterone (DHEA). This regulation of acupuncture on sex hormone levels
in female rats with PCOS was also demonstrated in a study.[2] Chen et al[24] also showed that acupuncture could regulate autophagy in ovarian granulosa cells
through the PI3K/AKT/mTOR pathway mediated by LncMEG3. In addition, it was also demonstrated
that LncMEG3 could target miR-21-3p to inhibit the early and late apoptosis of ovarian
granulosa cells in PCOS rats,[24] which revealed the significance of acupuncture in the treatment of PCOS. For the
study of acupuncture intervention in PCOS rat models, Xing et al[25] provide another insight into the mechanism of acupuncture in the treatment of PCOS,
suggesting that acupuncture can improve endometrial angiogenesis by activating the
PI3K/AKT pathway, thereby promoting endometrial receptibility and the number of implant
sites in PCOS rats, providing a more theoretical basis for clinical application.
Moxa-moxibustion
In recent years, experimental research on the effects of moxa-moxibustion on female
reproductive health has also been developed. Jin et al[26] showed that moxa-moxibustion intervention before or in the early stage of DOR in
Sprague–Dawley (SD) rats can improve ovarian function, and its protective effect is
related to the androgen receptor mediated androgen balance. It is worth noting that
the treatment course of moxibustion before DOR occurs needs to be longer than that
of moxa-moxibustion in the early stage of DOR to achieve the same ovarian protection
effect. As for the study of moxa-moxibustion intervention before the occurrence of
the disease, Shen et al[27] found that moxibustion pretreatment can significantly improve the estrus cycle of
rats with POI, regulate the levels of E2, AMH, FSH, and LH in serum, inhibit the apoptosis of ovarian granulosa cells, protect
the ovarian function of POI rats, and thus improve the fertility of POI rats. When
moxibustion intervention was performed during the occurrence of the disease, Li et
al[28] demonstrated that moxibustion could improve tripterygium glycoside (TGS) suspension-induced
ovarian function decline and inhibit ovarian granulosa cell apoptosis in DOR rats
by regulating PI3K/AKT signaling pathway, which was consistent with the previous study.[25]
Similarly, the efficacy of moxibustion intervention after the occurrence of female
reproductive system diseases in animals has been demonstrated. Moxa-moxibustion intervention
can reduce the NLRP3 inflammasome activated by TGS-damaged ovarian tissue and follicular
development in rats and improve the inflammatory microenvironment by activating Nrf2/HO-1
pathway.[29] However, whether NLRP3 over-activation is Nrf2/-HO-1 dose-dependent needs to be
further studied. For the rat model of POI, moxibustion can improve the ovarian reserve
function of cyclophosphamide (Cy)-induced POI rats by reducing mitochondrial dysfunction
and NLRP3 inflammatory activation,[29] which may also be a new strategy for the treatment of POI.
Electroacupuncture
Electroacupuncture is a treatment method that originated from TCM acupuncture and
moxibustion. It plays an important role in the treatment of primary insomnia, anxiety,
depression, and persistent pain[30]
[31] by combining traditional acupuncture procedures with electrical stimulation.[32] In recent years, electroacupuncture has made progress in the treatment of ovarian
injury.
Studies have shown that electroacupuncture plays an important role in the treatment
of SD rats with PCOS. It can improve the disordered estrous cycle, ovarian tissue
morphology, and hormone levels of FSH, LH, and E2 in rats with PCOS.[33]
[34]
[35]
[36] Concurrently, it also has a similar therapeutic effect on the improvement of symptoms
in PCOS mice such as C57BL/6J mice and female mice of the Institute for Cancer Research.[37]
[38] In addition, the mechanism of electroacupuncture improving the symptoms of PCOS
rats has also been developed. Shen et al[36] found that electroacupuncture may improve the gonadal axis function of PCOS rats
through the expression of hypothalamic Kisspeptin protein. Cong et al[33] also clarified the ability of electroacupuncture to resist the effects of PCOS by
inhibiting endoplasmic reticulum stress-mediated apoptosis and autophagy of ovarian
granulosa cells. In addition, electroacupuncture can also improve the reproductive
characteristics of PCOS rats by regulating hypothalamic neuropeptide Y and growth
hormone levels,[34] regulating Alas2-mediated apoptosis and mitochondrial function,[39] and regulating kisspeptin-GnRH/LH pathway through androgen activity attenuation.[35] Chen et al[40] showed that electroacupuncture also had a certain promoting effect on ovarian function
and menstrual cycle of POF mice. For rats with DOR, the effect of electroacupuncture
on improving ovarian function and hormone levels can be achieved by regulating the
expression of GSH-related regulatory enzyme protein and mRNA in the ovary and improving
the body's ability to resist oxidative stress.[41]
Discussion
In the treatment of ovarian injury, TCM moxibustion has gradually attracted attention.
However, there are still some controversies and inadequacies in this field.[42] This review summarizes the clinical efficacy and experimental research progress
of TCM moxibustion in the treatment of ovarian injury, aiming to provide reference
and enlightenment for further research.
TCM theory believes that the ovary is an important organ of the female reproductive
system, which is mainly responsible for the growth and development of eggs and the
secretion of female hormones, and plays an important role in female fertility and
health. When the ovary is affected by trauma or internal diseases, it may lead to
abnormal ovarian function and even affect fertility. Therefore, treatment of ovarian
damage is essential to maintain women's health and fertility. In terms of clinical
efficacy, TCM moxibustion has shown significant effects in improving ovarian function,[11]
[14] increasing pregnancy rate,[43] and regulating hormone levels.[13] The clinical effect of its combination with Western medicine or TCM is more significant.[16] It should be noted that TCM moxibustion therapy for ovarian injury needs to comprehensively
consider the specific conditions of the patient, such as age, etiology, course of
disease, and other factors, and combine with other TCM treatment methods such as herbal
medicine for comprehensive treatment to achieve better efficacy. At the same time,
when receiving TCM moxibustion therapy, patients also need to cooperate with the guidance
of doctors, pay attention to regulate diet, living habits, etc., so as to improve
the therapeutic effect.
In terms of experimental research, the therapeutic effect of TCM moxibustion on ovarian
injury is supported by experimental evidence. For example, moxibustion can improve
the estrus cycle of mice,[37] inhibit apoptosis of rat ovarian granulosa cells,[28] and regulate hormone balance.[44] Interestingly, these studies covered moxibustion interventions before, during, and
after the occurrence of ovarian damage, and all of them were able to obtain significant
effects. These findings suggest that moxibustion intervention can be applied in the
prevention, treatment, and recovery of ovarian injury.
Conclusion
TCM moxibustion therapy has potential advantages and broad prospects in the treatment
of ovarian injury, which can improve ovarian function, maintain the stability of endocrine
level, and, combined with other treatment methods for comprehensive treatment, can
achieve better therapeutic effects. However, there are still some controversies and
insufficiencies in the existing research. Future research should focus on the following:
(1) The mechanism and advantages of TCM moxibustion in the treatment of ovarian injury
should be further explored. (2) The advantages and disadvantages of TCM moxibustion
therapy and other treatment methods should be further explored in terms of efficacy
and safety. (3) The influence of individual differences on the treatment effect should
be paid attention to, so as to provide more accurate treatment for clinical practice.
(4) At present, the experimental mechanism of heat-sensitive moxibustion on ovarian
injury is lacking. At the same time, it is hoped that through further research, more
possibilities of TCM moxibustion therapy in the treatment of ovarian injury can be
explored, so as to provide patients with a safer and more effective treatment method.
