In a number of gynecological diseases, such as extensive purulent lesions of the uterus and appendages, some forms of endometriosis and ovarian tumors, one has to resort to radical surgical interventions – removal of the ovaries and uterus. Total oophorectomy performed at childbearing age is accompanied by complex reactions of the neuroendocrine system that characterize the process of adaptation of the female body to new conditions. Properly selected hormone replacement therapy will help to alleviate the patient's condition and prevent the development of diseases associated with the removal of the ovaries.
In women of reproductive age, estrogens (estradiol, estrone and estriol), progesterone and androgens are synthesized in the ovaries. Removal of the ovaries leads to a sharp decrease in the level of the most biologically active estrogen — 17β-estradiol (E2), already in the first weeks after oophorectomy, it can decrease to trace values. The level of gonadotropins increases, and the FSH content rises earlier and reaches a higher level compared to LH.
The main estrogen circulating in the blood of operated women is estrone. The latter is formed from androgens as a result of extragonadal aromatization. In overweight women, the rate of conversion of androgens into estrogens and the concentration of the latter in the blood is higher than in thin women.
In adipose tissue, these processes can be enhanced by an increase in the aromatase activity of fat cells due to an increased level of FSH. It has been established that in women of reproductive age, 49% of testosterone, the most active androgen, is synthesized in the adrenal cortex, 17% is formed by peripheral conversion from other steroid precursors, and 33% is synthesized in the ovaries. The ovaries also produce about 60% androstenedione and 20% dehydroepiandrostenedione. Thus, total oophorectomy can lead to a decrease in androgen levels in operated women due to the exclusion of the ovarian fraction of testosterone and its precursor androstenedione.
Fundamental research in recent years has shown that different types of estrogen, progesterone and androgen receptors are located not only in the main target organs (uterus and mammary glands). They are found in the central nervous system, bone tissue cells (osteoblasts and osteoclasts), vascular endothelium, myocardiocytes, connective tissue fibroblasts, urogenital tract, in the mucous membrane of the mouth, larynx, conjunctiva, and large intestine.
The hormonal effect is determined not only by the degree of binding of the hormone to the receptor, but also by the kinetics of the hormone-receptor complex in the nucleus, the stability of the complex. The concentration of receptors in a tissue determines its sensitivity to the hormone; tissues considered to be insensitive to hormones are characterized by a low concentration of hormone receptors.
Disease risks associated with oophorectomy
A sharp deficiency of sex steroids and, above all, estrogen causes systemic changes in organs and tissues due to a violation of hormonal homeostasis. The syndrome that develops after total oophorectomy is characterized by the development of neurovegetative, psycho-emotional and metabolic-endocrine disorders.
Somatic manifestations of total oophorectomy include classic vasomotor symptoms — hot flashes and night sweats in at least 70% of women. The frequency of hot flashes ranges from single to several dozen per day. They last for 1 year or many years. Hot flushes with profuse sweating are the earliest and specific symptoms of ovarian shutdown.
Headaches, dizziness, palpitations at rest, paresthesia, general weakness and fatigue occur already in the first weeks after total oophorectomy in 42-68% of patients. Neuropsychiatric disorders are manifested in the form of emotional lability with irritability, tearfulness, sleep disturbance, appetite, decrease or loss of libido.
Vaginal dryness — a very important symptom of PTSD. The thickness and moisture of the squamous epithelium of the vagina depend on estrogens, and a decrease in their concentration in serum leads to thinning and dryness of the vaginal mucosa. Dyspareunia, combined with a decrease or loss of libido, leads to sexual disharmony, and in some cases to the impossibility of sexual activity.
Estrogen deficiency is the cause of atrophic changes in the genitourinary system, which develop in 40-60% of patients. Women with SPTO often complain of frequent urination, dysuria, and urgency. Stress incontinence often accompanies PTSD. Atrophic vaginitis, recurrent cystourethritis, urinary incontinence, nocturia have an extremely negative impact on the quality of life of a woman.
Estrogen deficiency in SPTO leads to accelerated aging processes, reduced turgor and thinning of the skin, rapid appearance of wrinkles, increased dryness and brittleness of hair and nails. Non-specific symptoms that occur after total oophorectomy include muscle and joint pain, atrophic conjunctivitis, laryngitis, xerostomia, early development of glaucoma.
Spongy matter is at particular risk due to its large surface area. Even after minimal or moderate trauma, bone fracture can occur. Prescribing HRT immediately after surgery can completely block the bone loss that occurs after ovariectomy.
Hormonal background and its correction after hysterectomy
Syndrome, accompanied by a lack of estrogens, can occur not only after ovariectomy, but also after hysterectomy (HE). It is known that hysterectomy performed at reproductive age adversely affects the anatomical and functional state of the ovaries, leading to a decrease in the level of estradiol and the appearance of signs of an estrogen deficiency state.
This symptom complex, which occurs in a significant proportion of patients of reproductive age after removal of the uterus, characterized by the development of specific, psychoneurovegetative, sexual, urogenital, vascular and other estrogen-deficient conditions, is considered as a posthysterectomy syndrome.
The leading factor in the pathogenesis of post-hysterectomy syndrome is the occurrence of a deficiency of ovarian hormones, therefore, in order to correct these symptoms, HRT is used. Some authors prescribe estrogen monotherapy for this purpose. However, when choosing a hormonal drug for the relief of post-hysterectomy syndrome, it is necessary to proceed from the gynecological pathology that was the indication for hysterectomy, concomitant extragenital pathology, and the state of the mammary glands.
Hormone replacement therapy after total oophorectomy
The main and most pathogenetically substantiated method of treatment after total oophorectomy is hormone replacement therapy. The purpose of such therapy — pharmacological replacement of lost ovarian hormonal function.
Modern drugs use only natural hormones or their analogues in doses sufficient to treat early symptoms and prevent long-term effects. The appointment of HRT immediately after surgery contributes to the smooth adaptation of the woman's body to the conditions of an acute deficiency of sex steroids and prevents the development of postovariectomized syndrome. Against the background of taking sex hormones, the aging process of the skin slows down, affective disorders decrease or disappear, sexual desire is maintained, and the quality of life improves.
The duration of the HRT course may be different. It is believed that after oophorectomy, the minimum period for which HRT is prescribed is 5-7 years. The choice of therapy regimen depends on the age of the woman, the disease that caused the surgical intervention, the presence of risk factors, the extent of the operation, as well as the characteristics of clinical signs and the results of instrumental examination. It should be noted that the vasomotor manifestations of SPTO weaken or disappear after a few months after the start of treatment. However, the therapeutic and prophylactic effect in relation to the cardiovascular, bone and central nervous systems is manifested only with long-term (for 3–5 years or more) therapy.
Indications for HRT:
- hot flashes, night sweats;
- depression, sleep disturbance;
- genitourinary (urogenital) disorders — dyspareunia, vaginal dryness, frequent urination, dysuria, urinary incontinence;
osteoporosis.
HRT is also recommended for people with risk factors for osteoporosis, cardiovascular disease, Alzheimer's disease.
Absolute contraindications to the appointment of HRT are:
- estrogen-dependent malignancies: breast cancer, endometrial cancer;
- acute thromboembolic venous disease;
- severe diseases of the liver and kidneys with impaired functions;
- abnormal bleeding of unknown origin from the genital tract;
- an established or suspected pregnancy.
Before prescribing HRT, a gynecologist's examination, mammography, cytological examination of smears from the cervix, ultrasound of the pelvic organs are carried out.
As part of modern HRT preparations, estrogens are mainly used — 17ss-estradiol, estradiol valeriate, estriol. The first 2 are active estrogens, providing a stable therapeutic effect and the absence of postovariectomy symptoms while taking the drug. Estriol — weaker estrogen, but it has a pronounced positive effect on the mucous membrane of the urogenital tract and is effective in the treatment of genitourinary disorders. There are also conjugated estrogens obtained from the urine of pregnant mares. They have a biological effect similar to natural estrogens.
There are various ways of introducing HRT into a woman's body: in the form of oral tablets, transdermal HRT, vaginal suppositories and creams, subcutaneous implants.
In women for whom there are contraindications to the appointment of HRT, herbal and homeopathic preparations are used (climactoplan, climadion, remens, climac-heel, sigetin). These drugs have a positive effect on the vegetovascular and neuropsychic manifestations of SPTO, but do not prevent the development of pathology in the cardiovascular, bone, and urogenital systems.
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