Women are the primary participants in the reproductive process and the primary recipients of reproductive health services. As such, women are critical in reproductive health. Our concern for women’s reproductive health is also not only about the female reproductive process, but also about the good physical, mental and psychological state of women throughout their lives.
A. Normal ovarian function is the foundation of women’s health
The ovaries are the most important reproductive organ of women and have two main functions: reproductive function and endocrine function. The reproductive functions of the ovaries include the recruitment and development of follicles, the maturation and ovulation of follicles, and the formation and degeneration of the corpus luteum. This process is normally the necessary foundation for the formation of the mature oocytes of the female gametes necessary for human reproduction. The endocrine function of the ovaries refers to their secretion of sex hormones (estrogen, progesterone, androgen) and peptide hormones and growth factors, which are extremely important for reproduction and the body.
2. The important role of ovarian function on women’s health
(1) Important role for female reproductive health: The ovaries produce mature oocytes, which are essential for reproduction, and the endocrine function of the ovaries also plays a crucial role in reproduction.
The functions of estrogen produced by the ovaries include
①Promote the development and maturation of female reproductive organs and lay the basic conditions for reproduction.
(2) Stimulating and maintaining the development of secondary sexual characteristics and maintaining sexual desire.
(3) The estrogen secreted during follicular development promotes the proliferation of the endometrium, which is a prerequisite for the progesterone secreted after ovulation to exert its effect on the endometrium.
The progesterone produced by the ovaries is mainly in the form of progesterone and its functions include.
① Promote the transformation of endometrial tissue to the secretory phase, thus providing conditions for embryo implantation after fertilization.
(ii) Reducing the excitability of the uterine muscle and its sensitivity to contractile hormones to maintain pregnancy.
(iii) To further develop and mature the mammary gland alveoli and prepare conditions for milk secretion after delivery.
Androgens, on the other hand, contribute to the development of the clitoris, labia and mons pubis of the external genitalia. Peptide hormones produced by the ovaries include activin, inhibin, and anti-mullerian hormone (AMH). They regulate follicle recruitment, growth and dominance, mainly directly or indirectly through the regulation of pituitary follicle-stimulating hormone (FSH) secretion. In addition, a variety of growth factors produced by the ovary are involved in the regulation of follicular growth and development through autocrine and paracrine forms.
Therefore, the female reproductive function depends on the joint coordination of the above hormones.
(2) Important role for women’s overall health: Estrogen not only plays an important role in regulating women’s reproductive health, but also protects the physical and mental health of the entire female body. Estrogen promotes the development of female secondary sexual characteristics, maintains women’s beauty and physical appearance, and is beneficial to women’s physical and mental health, contributing positively to women’s life and work. Secondly, estrogen also maintains the normal development of the vulva, vagina and uterus as well as the normal female pelvic floor structure, which not only enables the reproductive organs to function accordingly and prevents the prolapse of pelvic organs and the functional damage they bring, but also promotes a comfortable and harmonious sexual life. These are all very important parts of a woman’s personal and family life.
Estrogen also regulates the metabolism of the body: including sodium and water conservation, increasing blood volume and extracellular fluid; lowering cholesterol, alleviating atherosclerosis and reducing vascular permeability, thus providing good protection for the heart and brain vessels.
Estrogen also promotes muscle protein synthesis and plays a role in promoting pubertal development and growth. Estrogen has the effect of promoting bone densification and preventing osteoporosis. In addition, estrogen has significant effects on several systems of the body, including the nervous system, the genitourinary system and the skin system, and is instrumental in maintaining the health of the female body.
In addition, the small amount of androgens produced by the ovaries is essential for the initiation of sexual maturation and the normal distribution of body hair, as well as promoting protein synthesis and improving muscle mass. This is also very important for the overall health of women.
Thus, the functions of the ovaries are extensive. Women’s health is dependent on the normal functioning of the ovaries, and their diminution or even loss is bound to have a great impact on and threaten women’s health.
Definition and etiology of ovarian hypofunction and premature ovarian failure
1. Overview: The menopausal transition is from the appearance of endocrinological, biological and clinical features of menopause to the last menstrual period. The average age of menopause in women is 49.5 years, and the normal menopausal transition period is 1 to 2 years before menopause. The menopausal transition is a mandatory process throughout a woman’s life. However, the early decline in ovarian function due to various reasons that cause women to enter the age-inappropriate menopausal transition or even menopause are called hypovarian reserve function (DOR) [hypoplastic ovarian function (POI) or ovarian failure to respond (POR)] and premature ovarian failure (POF), respectively. With the rapid socioeconomic development, the postponement of women’s childbearing age, and various environmental and disease influences, the incidence of POI and POF is increasing year by year [1], and is now receiving widespread attention because of its great adverse effects on women’s health and life.
2. The concept or diagnosis of POI and POF: POI is described as amenorrhea, elevated gonadotropins, and estrogen deficiency before the age of 40 years, and there are no unified international diagnostic criteria. POI and POF are risk signs of decreased fertility or even loss of fertility, and early detection and appropriate ART treatment is an important area of assisted reproductive treatment. The Bologna International Diagnostic Criteria for POR were first proposed by the Society for Human Reproduction and Embryology in 2011 [3]. However, the cut-off value, the necessary conditions and the homogeneity of the population included in this criterion have shortcomings and need to be validated in further randomized controlled clinical studies with large samples [4].
POI or DOR progresses further and culminates in ovarian failure, the latter if it occurs early is defined as POF. POF is defined as women under 40 years of age, excluding pregnancy, with more than 4 months of amenorrhea and at least 2 basal blood FSH over 40, U/L at 1 month intervals. the prevalence of POF in the general population is 1 to 3% [5]. Premature ovarian failure implies early loss of reproductive capacity in women. In the POI stage, special attention should be paid to the salvage of reproductive capacity and resolution of fertility problems. After ovarian failure, the focus of management shifts to maintaining the organism in good condition. The identification of diagnostic criteria for ovarian hypofunction and premature ovarian failure can help to identify these women early and provide early countermeasures to ensure that they fulfill their dreams of fertility as well as to ensure their good physical health and quality of life.
POI and POF seriously affect the reproductive and physical health of women
1. Immediate effects
(1) Fertility decline or loss, POI and POF on the most serious harm to women is the decline or loss of fertility. It is well known that as women age, their fertility gradually declines. One of the most important factors affecting the success rate of ART is the ovarian reserve function. When ovarian reserve function decreases, ovulation will not be able to obtain enough eggs to select good quality embryos for transfer and pregnancy rates will be significantly lower. The impact of POF is even greater, with a natural pregnancy rate of less than 5% to 10%. Most women with POF who undergo ART are likely to end up with donor eggs or adoption due to the unavailability of eggs. The inability to use her own eggs to obtain a pregnancy is a very hard blow to the woman and her family. The loss of fertility can easily lead to the breakup of the family, which will further increase the suffering of the woman and the family.
(2) Abnormal uterine bleeding, ovarian hypofunction and premature ovarian failure patients are prone to anovulatory abnormal uterine bleeding due to fluctuations in ovarian function. It often manifests as menstrual disorders and increased menstrual flow. In severe cases, sudden and massive uterine bleeding may occur, causing severe anemia and shock. Long-term anovulation or sporadic ovulation may also lead to excessive hyperplasia of the endometrium, which may cause cancer and seriously affect women’s health.
(3) Perimenopausal symptoms and psychological state of distress, POR and POF lead to fluctuation or reduction of sex hormones will cause a series of physical and mental psychological symptoms. The decrease of estrogen leads to instability of vasodilatory function, causing hot flashes and night sweats. Some patients may also cause psychoneurological symptoms, including inattention, emotional agitation and irritability or depression, and inability to control themselves, which seriously affect women’s work and life. Autonomic disorders such as dizziness, insomnia, tinnitus, palpitations and other discomforts add to women’s anxiety and depression, and are likely to seriously affect women’s performance at work and in life as well as the coordination of interpersonal relationships. In addition, early menopause is usually a serious blow to women’s psychological well-being, and it will significantly affect their emotional and psychological state. Women who experience early menopause have significantly higher depression and anxiety scores than normal women, and body image maintenance and sexual function are significantly affected. Moreover, psychological symptoms are more pronounced in secondary POF caused by surgery or radiotherapy than in primary POF. Studies have shown that women with drug-induced early menopause or primary POF are generally in a state of mild anxiety, whereas patients with POF due to surgery are in a state of moderate anxiety. Further, patients with secondary POF are more negative than primary POF in terms of motivation to live and maintain their physical status. Therefore, we need to pay attention to the psychological impact of early menopause on women, especially in patients with secondary POF, for whom timely psychological guidance and treatment should be provided. For such women, active lifestyle and seeking psychological guidance is the first line of treatment, and its status is even higher than that of hormone replacement therapy.
2.Long-term effects
(1) Neurological effects, POF accelerates the decline of cognitive power. Estrogen deficiency will lead to memory loss, cognitive impairment and dementia. The incidence of Alzheimer’s disease (AD) is significantly higher in patients with premenopausal ovariectomy without hormone replacement, and Alzheimer’s disease not only causes partial or complete loss of social adjustment ability, but also this severe intellectual disability will be experienced for several years or even decades, which is a heavy burden for the patient, his family and society.
(2) Osteoporosis, the rate of bone loss peaks 3 years before menopause, and the rate of bone loss in ovarian failure due to medically induced injury is twice as fast as the rate of bone loss in natural menopause. Osteoporosis is accompanied by severe pain and body deformity, and in severe cases is complicated by fractures. The fractures may be mild enough to restrict movement, or severe enough to cause disability or even long-term bed rest, followed by cardiovascular and cerebrovascular complications, lung infections, and bed sores due to the restricted movement. The medical and socio-economic impact of osteoporosis is enormous, not only for personal health.
(3) Cardiovascular disease, low serum estrogen levels may partially explain the negative changes in lipids and carbohydrates that occur rapidly during and after the menopausal transition, with similar changes in lipids and carbohydrates in women with POF at an average age of 31 years and in women with normal menopausal transition at an average age of 52 years. Disturbances in lipid metabolism are strongly associated with the development of cardiovascular accidents, and postmenopausal status has been shown to be an independent risk factor for the development of cardiovascular disease. It has been well documented that early menopause can increase the risk of cardiovascular morbidity, and increased rates of myocardial infarction and angina pectoris have been shown to be associated with menopause. Thus, a joint statement by European cardiologists and obstetricians and gynecologists on the management of cardiovascular disease risk in perimenopausal women highlights the importance of focusing on the cardiac effects of POI and POF.
(4) Genitourinary tract symptoms and effects on sexual function. Chronic estrogen deficiency can lead to genitourinary tract atrophy, resulting in painful intercourse and difficulty in sexual intercourse. In addition, estrogen causes deficiency of vaginal epithelial glycogen, which leads to thinning and damage of the vaginal epithelium, resulting in recurrent vaginal infections. The lack of androgens causes low libido, sexual arousal disorders, and sexual disharmony. Sexual disharmony may cause serious damage to both spouses, both physically and psychologically, and may even lead to the breakup of the family and indirectly affect social stability.
(5) Effects on the skin: The skin is the fastest and most obvious target organ for estrogen. Prolonged low estrogen can lead to thinning of the skin and a decrease in collagen content. In addition, estrogen deficiency reduces skin keratin formation and loss of skin barrier function. Therefore, patients with POI or POF can accelerate skin aging due to long-term estrogen deficiency, resulting in decreased skin elasticity, sagging and dry skin, and affecting women’s appearance. This is undoubtedly an added problem for women who are more in pursuit of beauty in the new era.
Therefore, POI and POF not only threaten women’s reproductive health, but also seriously affect women’s physical and mental health, and must pay great attention to its impact on women’s quality of life and health.
Fourth, POI and POF prevention and treatment strategies
1, prevention of POI and POF, first of all, we should strengthen publicity and education, strengthen awareness, so that patients independently avoid factors that may lead to ovarian function damage, to protect ovarian function. This includes active treatment of primary diseases, avoiding exposure to toxic chemicals, maintaining good lifestyle habits and a positive attitude, good contraception, reducing the number of abortions, and reasonable prevention of pelvic infections. Secondly, as medical workers, we should give correct guidance and advice to patients to avoid medically induced ovarian damage. For example, we should grasp the indications for pelvic surgery, try to avoid operations that may have an impact on ovarian function such as injury to ovarian tissue during surgery, and try to preserve the remaining ovarian tissue. For patients who must undergo chemotherapy, try to use local chemotherapy as well as the use of reasonable drugs with stronger targeting. For patients who need to receive radiotherapy, protective measures must be done, using localized post-mounted radiotherapy techniques as much as possible and taking measures to protect ovarian function such as ovarian transposition if necessary.
2. Treatment of POI and POF, the decline of ovarian function is almost irreversible, and POI should be treated promptly once detected. For patients without fertility requirements, they should be advised to undergo hormone replacement therapy under close monitoring when indicated to improve their quality of life as well as to protect the health of other organs of their body.
For patients with fertility requirements, various assisted reproductive technologies should be actively adopted. In particular, fertility preservation, including embryo freezing, freezing of mature or immature eggs and freezing of ovarian tissue, may be considered prior to treatment for patients with infertile tumors who require radiotherapy. These techniques offer new hope for women whose ovarian function has been compromised to address fertility issues.
So, for women’s reproductive health and physical and mental well-being, normal ovarian function is indeed their jewel!