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Advances in diagnosis and treatment of perimenopausal syndrome

  • Wanying Chen , Mengjuan Chen , Huimin Tang , Weiwei Wei , Panqiu Shao , Shulan Dou , Jia Wu , Bingying Lu , Ruxia Shi EMAIL logo and Jiming Chen EMAIL logo
Published/Copyright: December 22, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

With the development and progress of society, people’s average life expectancy has increased, and relevant literature reports that the number of postmenopausal women in China continues to increase. With lifespans extended, the transition period and post-menopause period have become the longest essential period in every woman’s life. The life quality of women troubled by perimenopausal syndrome has been significantly reduced, which also places a burden on families and society. It is well known that hormone replacement therapy plays a vital role in improving women’s menopause-related symptoms and is the most effective medical measure. With research ongoing into the treatment of menopausal symptoms in different patients, dose size, treatment duration, and medication regimens for hormones are still hot topics of discussion. This article reviews the definition, clinical diagnosis, staging, clinical manifestations, and treatment of menopause and explores the current diagnosis and treatment scenarios of perimenopausal syndrome.

Keywords: perimenopausal syndrome; hormone replacement therapy; low dose; efficacy

Menopause is a life stage that every woman must go through. According to statistics, China had 167 million postmenopausal women in 2011, and it may reach 280 million by 2030. With life expectancies extended, more than one-third of a woman’s lifetime is in the postmenopausal stage. Therefore, it is conceivable that menopause-related health management and prevention and control of perimenopausal diseases have become important public health issues, which clinicians, scientists, and wider society should pay attention to [1]. Ovarian function failure is the leading cause of menopause. With the decline of ovarian function, the hypothalamus–pituitary–ovarian axis in women’s bodies becomes out of balance, resulting in related symptoms. This series of physical and psychological health problems is called perimenopausal syndrome and includes both short-term and long-term symptoms. Prominent symptoms include hot flashes, sweating, palpitations, paresthesia, irritability, depression, etc.

1 Clinical diagnosis and staging of menopause

The clinical definition of menopause refers to the permanent cessation of a woman’s monthly menstruation. That is, a woman aged over 40 years who has no menstrual cramps within 12 months of their last menstrual period can be diagnosed as experiencing menopause once pregnancy and other related diseases have been ruled out. The essence of menopause does not simply refer to the presence or absence of menstruation but refers to the failure of female ovarian function, meaning that the female reproductive system is in a state of functional “exhaustion.” With the decline in ovarian function, the estrogen in the human body will also fluctuate and decline, and women will often have a series of physical and mental symptoms. The Stages of Reproductive Aging Workshop + 10 was announced in 2011 (Figure 1). It is currently a worldwide recognized staging benchmark for female reproductive aging [2]. The arrival of menarche marks the start of the female reproductive period. The duration of this lifecycle is variable. As age increases, the ovarian endocrine axis matures, and the menstrual cycle gradually turns from irregular to regular, including an early period (−5), peak period (−4), and late period (−3). In the latter period, women’s fertility has begun to decline, and the period can be further divided into two subperiods −3b and −3a. In the −3b subperiod, women’s menstruation can remain regular, and in the −3a subperiod, women’s menstrual cycle begins to show subtle changes, especially cycle shortening. Women’s menopausal transition period can be divided into early (−2) and late (−1) periods, and the change in the menstrual cycle is the main evaluation criteria. The menstrual cycle length change (that is, menstrual disorder) is a sign of the early transition period for menopausal women. Specifically, it refers to a length change in 2 or more adjacent menstrual cycles that is ≥7 days in 10 menstrual cycles. Menstrual cycle extension being ≥60 days is a sign of late menopause transition. Postmenopause includes early (+1) and late (+2) periods. The early period can be divided into three sub-periods, namely +1a, +1b, and +1c, of which the +1a sub-period refers to 1 year after the last menstrual period. The menopause transition period and the +1a sub-period are also known as perimenopause. Menopause can be clearly diagnosed only after the +1a sub-period ends. The +1b sub-period lasts for 1 year, the +1c sub-period lasts for 3–6 years, and the +2 sub-period is the late postmenopause. Menopause is also categorized into natural menopause and artificial menopause after intervention. It means the reduction of women’s ovarian function. If a woman receives an artificial hysterectomy but her ovarian function is normal, she does not belong to the menopause category. Patients with perimenopausal syndrome may suffer from a series of other systemic symptoms, and medical workers need to rule out related organic diseases, such as thyroid dysfunction, cardiovascular and cerebrovascular diseases, mental diseases, and bone and joint system diseases. The laboratory manifestations of female ovarian function decline generally require the detection of sex hormone levels. When the anti-Müllerian hormone (AMH) is less than 0.2 ng/mL, the follicle-stimulating hormone is >40 U/L, and the estrogen is <10–20 pg/mL, it indicates that the woman is about to go into menopause, and AMH is generally undetectable in the blood of postmenopausal women.

Figure 1 Stages of female reproductive system aging.
Figure 1

Stages of female reproductive system aging.

2 Clinical manifestations of perimenopausal syndrome

2.1 Menstrual disorders

Irregular menstrual cycles, long menstrual periods and increased or decreased menstrual blood volumes are the main menstrual-related manifestations among women. Other studies have shown that 82% of perimenopausal women have problems related to amenorrhea, a prolonged menstrual cycle, and/or oligomenorrhea, of which 18% have symptoms of increased menstrual blood volumes, menostaxis, or short menstrual cycles. It was found that 19% of the patients with short menstrual cycles had malignant changes such as histological precancerous lesions. Moreover, abnormal uterine bleeding during perimenopause is primarily due to anovulatory dysfunctionality, often manifested in weeks or months of menopausal symptoms, followed by sudden massive vaginal bleeding or irregular uterine bleeding, while anemia, infection, and shock are more serious complications [3].

2.2 Vasomotor symptoms (VMS)

Hot flashes are the main manifestation of VMS and a characteristic symptom of ovarian hypofunction in women. The main pathogenesis is that the fluctuation of estrogen and other endocrine hormones in the female body leads to vasomotor dysfunction, resulting in hot flashes. The incidence of hot flashes in menopausal women may reach as high as 75%, and the most common manifestation is redness of skin on the face, chest, and neck, followed by sweating, which usually lasts for minutes and can occur several times a day. In more severe cases, the symptoms can occur dozens or more times a day [4].

2.3 Symptoms of autonomic disorders

Headache, palpitations, insomnia, dizziness, and tinnitus are common symptoms of autonomic disorders. Common neuropsychiatric symptoms, such as agitation, irritability, depression or anxiety, and a lack of self-control, may be accompanied by hypomnesis. According to relevant studies and statistics, the incidence of neurological symptoms in menopausal women is as high as 58%. The specific manifestations reported are depression (accounting for 78%), irritability (accounting for 72%), apathy (accounting for 65%), insomnia (accounting for 52%), and headache (accounting for 35%) [5,6].

2.4 Long-term symptoms

Genitourinary syndrome of menopause (GSM) is characterized by vaginal dryness, dyspareunia, and recurrent vaginal infections, as well as recurrent urinary tract infections such as dysuria, odynuria, and urgent urination. Relevant literature shows that more than 50% of menopausal women will experience symptoms related to the genitourinary system, largely due to the reduction of postmenopausal hormone levels, which leads to different degrees of atrophic changes in the human reproductive system. This includes atrophy of the labia minora in postmenopausal women, thinning and less flexibility of mucous membrane at the vaginal wall, vaginal dryness, dyspareunia, and persistent vaginal infections caused by varying degrees of cervix and uterine atrophy, as well as endometrial inflammation, pyometra, and more [7]. Osteoporosis is due to the lack of estrogen in postmenopausal women, leading to an increase in bone absorption and massive loss of bone mass, which in turn causes a significant decrease in bone content and bone strength and gradually develops into osteoporosis [8]. Some studies have shown that estrogen can effectively reduce the incidence and mortality of cardiovascular- and cerebrovascular-related diseases. The reduction of estrogen in women in menopause reduces the protective effect on the cerebrovascular system, resulting in functional degeneration of the cardiovascular and cerebrovascular systems and increasing the risk of cardiovascular and cerebrovascular diseases in postmenopausal women, such as coronary heart disease and arteriosclerosis [5,9] (Figure 2).

Figure 2 Menopause clinic flowchart.
Figure 2

Menopause clinic flowchart.

3 General treatment of perimenopausal syndrome

After women enter the perimenopausal period, their basal metabolic rate will decrease. Without proper management, weight will increase. Some studies have shown that weight gain is a risk factor for knee joint disease, as the occurrence of knee joint disease in overweight and obese people is significantly higher than that in people of a normal weight [10]. Weight control through diet management can reduce or avoid bone and joint damage, and control of coffee, strong tea, and alcohol intake can also reduce bone loss. According to the Global Burden of Disease Study, unreasonable diet is the most significant cause of disease and death among Chinese residents. Among the causes of death among Chinese residents in 2017, 3.1 million deaths can be attributed to their unreasonable diet [11]. Therefore, healthy diet management is critical for perimenopausal patients. The Chinese Nutrition Society recommends that Chinese women in menopause consume whole grain fiber and ensure enough intake of fresh fruits and vegetables every day. Specifically, they should eat fish-based food at least twice a week, reduce sugar and oil intake, and limit salt and alcohol intake. The daily intake of sugar should be ≤50 g, salt should be ≤6 g/day, oil should be 25–30 g, and alcohol content should be ≤15 g. Smoking is not recommended, and sufficient water should be consumed, which is recommended to be 1,500–1,700 ml per day. Regular aerobic exercise is recommended every day to reach a total of 150 min per week, and resistance exercise should be carried out twice to thrice a week to increase muscle mass and strength in the body. The 2020 WHO guidelines on physical activity and sedentary behavior also mentioned that adults should set a target of 150–300 min of moderate-intensity and 75–150 min of vigorous-intensity physical activities [12]. A total of 6,000 steps of physical activity on average per day is recommended to enhance the overall health of menopausal patients. In terms of diet, the literature shows that the risk of all-cause mortality decreases by up to 12% among people with a high intake of whole grains, and there is a clear dose–response relationship between the two. Soy isoflavones, the main component of soybeans, can reduce bone absorption, increase bone density, and prevent osteoporosis. High doses (>90 mg/day) are beneficial to bone density of hip joints and lumbar spine. The intake of soy and its products can also reduce the risk of breast cancer. Every 10 mg/day increase of soy isoflavones can reduce the risk of breast cancer by 3%. More broadly, it was found that the consumption of soy and its products (soy intake >1.62 g/day, or tofu intake ≥14.4 g/day, or soy isoflavones at 26.3 mg/day) can greatly reduce the risk of breast cancer in women (especially postmenopausal women).

4 Hormone therapy for perimenopausal syndrome

Menopausal hormone therapy (MHT) is the most common and important treatment method for postmenopausal women. It refers to the artificial supplementation of estrogen and progesterone to improve a series of menopausal syndromes caused by low levels of estrogen and progesterone in the body. According to the Hormone Therapy Position Statement issued by the North American Menopause Society (NAMS) in 2017, supplemental hormone therapy is currently the most effective medical measure for the treatment of VMS and GSM [13]. Studies have shown that oral hormone therapy can significantly reduce the incidence of VMS during menopause and reduce their severity to significantly improve the overall quality of life for menopausal women [14,15]. Studies have shown that MHT can also reduce bone destruction by inhibiting the activity of osteoclasts to control the osteopenia degree in postmenopausal women. Women who start MHT treatment right before or after menopause can achieve the effect of primary fracture prevention [16,17]. The International Menopause Society proposed in 2017 the concept of “time window” [18]. The Global Consensus Statement on Menopausal Hormone Therapy in 2013 clearly stated that menopausal women younger than 60 years old or within 10 years of menopause are in a “time window” period, during which hormone therapy can generate the highest benefit, with relatively low risks of treatment [19].

4.1 Commonly used drugs for hormone therapy

4.1.1 Estrogens

Relevant studies recommend the use of natural estrogens, including 17β-estradiol, conjugated estrogens, and estradiol valerate. Preparations that can be absorbed through the skin include estradiol gel, estradiol patches including estradiol hemihydrate patches, and vaginal administration including conjugated estrogen ointment, estriol ointment, and prostalene vaginal capsules. Non-oral hormone replacement therapy (transdermal therapeutic system) is an important step forward in HRT in recent years, especially for postmenopausal women with chronic liver and gallbladder diseases, gastrointestinal tract diseases, and others who cannot tolerate oral administration. Non-oral estrogen supplementation perfectly avoids the first-pass effect of the human liver, with smaller stimulation to the liver and a smaller impact on metabolism. Therefore, non-oral hormones as complementary treatment regimens are advantageous as they can reduce the risk of cardiovascular and cerebrovascular diseases and venous thrombosis.

4.1.2 Progesterone

Micronized progesterone is a natural progesterone, and dydrogesterone is a reversal progesterone derivative, and also the drug most resemblant to natural progesterone. Relevant treatment guidelines also recommend that menopausal women use natural progesterone or the progestogen that is the closest to natural progesterone.

4.1.3 Compound preparations of estrogen and progesterone

The sequential preparations of estrogen and progesterone include estradiol/estradiol-dydrogesterone tablets and estradiol valerate/estradiol valerate and cyproterone acetate tablets. The continuous combined preparation of estrogen and progesterone is estradiol/drospirenone tablets.

4.1.4 Tibolone

7-Methyl-norethisterone is the main active ingredient of tibolone, which is a selective modulator of estrogenic activity. In addition to having good effects on menopause-related symptoms such as those present in mood, skeletal system, and atrophic vaginitis, it will not stimulate endometrial hyperplasia and will not increase the density of female breast tissue and the incidence of breast distending pain. For postmenopausal women with a uterus, tibolone treatment does not require progesterone to antagonize endometrial proliferation. Tibolone metabolites contain androgenic related activities, which can also effectively ease mood and increase libido.

4.2 Commonly used treatment regimens for MHT

4.2.1 Relevant treatment regimens using progesterone alone

It is primarily used in the early menopausal transition period. Their main purpose is to treat menstrual-related problems in the process of ovarian decline.

4.2.2 Treatment regimens using estrogen alone

It is only for postmenopausal women undergoing hysterectomy,

4.2.3 Combined use of estrogen and progesterone, including estrogen-progestin sequential regimens and estrogen-progestin combination regimens

4.2.3.1 Sequential regimen

It is primarily used in women who have an intact uterus, are in perimenopause or postmenopause but still wish to maintain menstrual-like bleeding. The regimens can be divided into cycle sequential ones and continuous sequential ones. The cycle sequential regimen refers to the use of estradiol valerate tablets/estradiol cyproterone tablets belonging to the cycle sequential compound preparation, with 1 tablet per day for a total of 21 days, and a pause in drug dosing for 7 days before the next cycle starts. Continuous oral or transdermal estrogen administration for 21–25 days can also be chosen, with progesterone added during the last 10–14 days. After the drug dose is paused for 3–7 days, the next cycle of treatment starts. The continuous sequential regimen refers to continuous application of estrogen without a stop, with progesterone added during the last 10–14 days of each month. Withdrawal vaginal bleeding is expected. Relatively speaking, the continuous sequential regimen uses estrogen without interruption, which is more beneficial for the control of menopause-related symptoms.

4.2.3.2 Continuous combination regimen

Primarily used for women who have an intact uterus and do not wish to have menstrual-like bleeding after menopause. In addition, for postoperative patients with endometriosis, the continuous combination regimen is generally recommended in the early stage to reduce the adverse effects of endometriosis on ovarian reserve. Daily continuous administration of estrogen (oral or transdermal) plus progestin can be chosen, or a combination preparation could be used, such as estradiol/drospirenone tablet, with 1 tablet per day. It is also administered continuously. The continuous combination regimen is easy to use, has a low rate of vaginal bleeding, and has good compliance.

4.3 Low-dose MHT

4.3.1 Overview of low-dose MHT

The type and method of MHT medication and the choice of therapeutic dose should be comprehensively analyzed according to the patient’s situation (such as the patient’s expected effect of the treatment and relevant health examination results). The hormone supplementary treatment with the most benefit can be prioritized after analysis of the patient’s condition. Each patient’s situation is different, so individualized treatment should be conducted during the consultation process. The NAMS stated in a 2008 statement that MHT should start from the lowest effective dose [20]. Generally, 0.625 mg/day conjugated estrogen or its equivalent dose is called a standard dose, and half of the standard dose is called a low-dose hormone, such as 0.3 mg/day conjugated estrogen, 1 mg/day estradiol valerate, and 1 mg/day l7-beta-estradiol. About 1/4 of the standard dose is called an ultra-low dose, such as 0.5 mg/day estradiol valerate and 14 μg/day transdermal estrogen. The use of preparations of lower-than-standard doses can also greatly improve and maintain patients’ quality of life and is more conducive to reducing adverse drug reactions.

4.3.2 Efficacy and safety of low-dose MHT

Hormone replacement therapy can significantly reduce menopausal symptoms associated with menopausal women, and guidelines for managing perimenopausal symptoms now recommend the lowest effective dose of estrogen. One study compared low-dose HRT (1 mg estradiol/2.5 mg dydrogesterone) and ultra-low dose HRT (0.5 mg estradiol/5 mg dydrogesterone) with placebo for 13 weeks, with all groups displaying positive therapeutic effects. The ultra-low dose group had significantly higher efficacy than that of the placebo group, and the incidence of vaginal bleeding was relatively low, which increased the users’ compliance and acceptance [21]. The Women’s HOPE study showed that low-dose hormonal components also improved related menopausal symptoms and provided some endometrial protection. The most unique therapeutic effect of MHT is that it can improve vaginal atrophy and related problems in women, especially dyspareunia. Its mechanism of action is to improve the maturation index of women’s vaginal cells, increase the number of vaginal wall cells, and enhance the local resistance of the vagina, thereby relieving vaginal discomfort and improving quality of life for women. The recommended best treatment plan is to choose low-dose hormones administered orally or vaginally. Relevant studies have shown that, even with topical treatment, the combined effect of lower doses of vaginal estrogen is better than that of higher doses. The effectiveness of low-dose hormone replacement therapy has been confirmed by a number of clinical studies. The shared conclusion of these studies is that, compared with standard-dose hormone replacement therapy, low-dose HRT can effectively relieve VMS and vulvovaginal symptoms in menopausal women, as well as prevent postmenopausal bone loss and reduce adverse effects. It can also improve the compliance of perimenopausal patients.

5 Non-hormonal drug options for perimenopausal syndrome

For perimenopausal syndrome, individualized treatment is always required, and the therapeutic effect and impact achieved for different individuals also vary greatly. For women who have no contraindications to hormone therapy and are willing to accept hormone therapy, hormone therapy can be recommended. However, for patients with contraindications to MHT or patients who are unwilling to receive hormone therapy, non-hormonal drug therapy is a good choice. Non-hormonal drugs include Chinese patent medicines such as Kuntai Capsules, Xiangshao Granules, and botanicals such as Black Cohosh.

A meta-analysis showed that the incidence of adverse reactions to Chinese patent medicine Kuntai Capsule in the treatment of perimenopausal syndrome was lower than that of estradiol valerate, suggesting that Kuntai is safer in the treatment of menopausal symptoms and can reduce breast distending pain, vaginal bleeding, and other adverse reactions. Studies have shown that the Kupperman score, breast tenderness, gastrointestinal discomfort, and other symptoms after treatment with Kuntai Capsules were lower than those treated with hormone therapy, and the difference was statistically significant. Therefore, Kuntai Capsules can also solve the troubles caused by menopause and improve the symptoms of perimenopausal syndrome. Kuntai Capsules are an option for perimenopausal patients who cannot or are unwilling to use hormone therapy. A controlled clinical trial showed that the use of Xiangshao Granules can effectively improve mood disorders in menopausal women, and the Kupperman score decreased significantly after medication. Black Cohosh is a pure natural botanical medicine extracted from cohosh plants using modern technology. It is non-hormonal and has no hormone activity but can produce hormone-like effects. Most variants are used to relieve hot flashes and sweating and lower the frequency of VMS in menopause. Chinese guidelines on menopause management and menopause hormone therapy (2018) also believe that the above drugs are helpful for the improvement of menopausal symptoms (Figures 3 and 4).

Figure 3 Treatment regimen selection.
Figure 3

Treatment regimen selection.

Figure 4 Re-examination and follow-up after treatment.
Figure 4

Re-examination and follow-up after treatment.

6 Summary and outlook

As women age, the number of primordial follicles in their ovaries also decreases progressively. When the number of follicles drops to a very low level, women will experience menopause, and a series of symptoms associated with menopause are called perimenopausal syndrome. With the development and progress of society, people’s quality of life and life expectancy continue to improve, and the duration of menopause also increases for women. Therefore, it becomes a significant and challenging task to address menopause-related issues for women. The hormone therapy currently widely used can address 70–90% of perimenopausal symptoms. With research progressing, individualized and low-dose therapy is proposed. It is found that the lower dose of drugs taken by menopausal women can not only reduce patients’ economic burden but also effectively relieve menopause-related symptoms to improve the quality of life for women who are troubled by menopause. Furthermore, they can also reduce the adverse reactions caused by hormone therapy.

MHT is currently the main treatment for menopause-related symptoms, but it is not the only treatment. For patients with absolute contraindications or who do not wish to use hormonal therapy, general therapy and non-hormonal therapy can also reduce perimenopausal symptoms. The effects and risks of ultra-low-dose hormone therapy for patients who have passed the window period and have severe symptoms still need to be further explored. For patients who are reluctant to accept hormone therapy or have contraindications, the efficacy, safety, and individualized treatment plan of non-hormone therapy still need more conclusive data, and the safety and efficacy of long-term treatment with traditional Chinese medicines combined with hormone therapy also need further research and discussion.

# Co-first authors: Chen Wanying, Chen Mengjuan, Tang Huimin.

  1. Funding information: This study was supported by grants from Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project (2022CZBJ074); the maternal and child health key talent project of Jiangsu Province (RC202101), the maternal and child health research project of Jiangsu Province (F202138), the Scientific Research Support Program for Postdoctoral of Jiangsu Province (2019K064), and the Scientific Research Support Program for “333 Project” of Jiangsu Province (BRA2019161).

  2. Author contributions: Wanying Chen, Mengjuan Chen, Huimin Tang,: manuscript writing, investigation, methodology, and validation; Weiwei Wei, Panqiu Shao, Shulan Dou, Jia Wu,: data collection, data curation and analysis; Bingying Lu,: data curation and analysis and draft editing; Ruxia Shi, Jiming Chen: study conceptualization, supervision, reviewing, manuscript writing, revising, and editing.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-02-25
Revised: 2023-08-24
Accepted: 2023-09-19
Published Online: 2023-12-22

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
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  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
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  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
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  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
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  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
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  245. Animal Sciences
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  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
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  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0754
Keywords for this article
perimenopausal syndrome; hormone replacement therapy; low dose; efficacy
Creative Commons
BY 4.0

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  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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