Hypoestrogenism in women

In the section on endocrine diseases and disorders of the endocrine glands of ICD-10, hypoestrogenism is a condition associated with a decrease in the production of female sex hormones (estrogens) by the ovaries and has the code E28.39.

As the main female sex hormones, estrogens play an important role not only in the reproductive function of women, but also in the normal functioning of other body systems, including the cardiovascular, musculoskeletal and central nervous systems. [ 1 ]

Epidemiology

The prevalence of premature ovarian failure among the female population is estimated by clinical statistics in the range of 0.3-1.4%.

Functional insufficiency of the female sex glands (hypogonadism) is the cause of hypoestrogenism in approximately one case per 2.5-3 thousand; in almost 35% of cases it is genetically determined; it is associated with the absence of menstruation (amenorrhea) in 10-35% of women.

About 50% of cases of hyperprolactinemia (diagnosed in less than 1% of women) occur in a prolactin-secreting pituitary tumor called a prolactinoma.

According to foreign specialists in reproductive medicine, menstrual cycle disorders due to increased physical activity are observed in almost half of female athletes, and a third experience amenorrhea.

Causes hypoestrogenism

The most likely causes of hypoestrogenism or estrogen deficiency are associated with a decrease in estrogen synthesis in primary ovarian failure, as well as their secondary (premature) failure in women under 40 years of age, caused by extensive inflammation of the ovaries, their cystic changes - in polycystic ovary syndrome, as well as surgical interventions and the use of certain medications. [ 2 ]

Also, estrogen production decreases with:

• isolated hypogonadotropic ovarian hypofunction;
• functional insufficiency of the hypothalamic-pituitary system (which controls the functioning of the sex glands) – due to damage or pathology of the hypothalamus and disruption of the gonadotropic function of the pituitary gland, which manifest in women with hypopituitarism and functional insufficiency of the sex glands – hypogonadism, in particular, with postpubertal hypothalamic hypogonadism;
• hypocorticism - chronic insufficiency of the adrenal cortex.

In addition, hypoestrogenism in women of reproductive age may occur as a result of hyperprolactinemia (increased prolactin production) – with the development of hyperprolactinemic hypogonadism or Chiari-Frommel syndrome.

If hypoestrogenism in young women is the result of pathology, then the physiological decrease in the level of estrogens (estrone, 17β-estradiol and estriol) in women during perimenopause, which precedes the onset of menopause, is not related to painful conditions, but is a natural stage of the fading of the functions of the glands of the female reproductive system. [ 3 ]

Risk factors

Endocrinologists note the following risk factors for low estrogen levels:

• age (the older the woman, the less estrogen is produced by the ovaries);
• delayed sexual development;
• presence of ovarian cysts and hormonal problems in the family history;
• ovarian or adrenal tumors;
• pathologies of the pituitary gland (including adenoma) and neoplasms in the hypothalamus;
• severe renal failure;
• functional disorders of the endocrine system;
• critically low body weight;
• passion for extreme diets for weight loss and eating disorders (anorexia);
• excessive physical exertion and stress;
• iatrogenic effects of radiation and chemotherapy;
• the use of pharmaceuticals, in particular steroids, opioids, psychotropic drugs, as well as drugs that inhibit the synthesis of estrogens - aromatase inhibitors (which are used in the treatment of neoplasms of the mammary gland and uterus).

There is a high risk of hypogonadism and ovarian dysfunction in autoimmune disorders (eg, hypoparathyroidism, Addison's disease), genetic syndromes (Turner, Kallmann, Prader-Willi), hemochromatosis.

Pathogenesis

In case of cystic changes in the ovaries, the pathogenesis of the disruption of their estrogen-producing function is usually caused by the alteration of granular and theca cells of the follicles, which provide steroidogenesis: the synthesis of pregnenolone from cholesterol, the conversion of pregnenolone into progesterone, and progesterone into androgens (androstenedione, testosterone and dihydrotestosterone), which are transformed into estradiol with the help of aromatase (P450Arom).

The decrease in estrogen production occurs due to degenerative changes in their granular cells and increased proliferation and/or insufficient activity of androgen-producing theca cells of the follicles (which leads to increased synthesis of follicular androgens).

In some cases of primary ovarian failure, the disruption of estrogen synthesis is of autoimmune origin and is associated with the presence of autoantibodies that damage the ovarian follicular apparatus. [ 4 ]

Estrogen deficiency in hypogonadism may be a consequence of impaired secretion and decreased levels of pituitary gonadotropic hormones – follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as well as gonadotropin-releasing hormone (GnRH) produced by the hypothalamus.

And with increased synthesis of prolactin in the anterior pituitary gland, the mechanism lies in the ability of this hormone to suppress the production of estrogen by the ovaries.

Symptoms hypoestrogenism

Don't be surprised that the first signs of hypoestrogenism are similar to the first signs of menopause, because any decrease in estrogen levels, including those caused by age (provided for by nature), has a similar clinical picture.

Low estrogen levels cause symptoms such as irregular or absent periods, hot flashes, night sweats, sleep disturbances (insomnia), frequent headaches, vaginal dryness (vulvovaginal atrophy), and decreased libido. [ 5 ]

In addition, memory deteriorates, mood often changes, and irritability, fatigue, and depression are observed. [ 6 ]

Complications and consequences

Hypoestrogenism can have long-term consequences and complications, the most significant of which are:

• absence of menstruation - secondary amenorrhea;
• ovulation disorders with partial or complete infertility;
• atrophy of mammary gland tissue;
• early menopause in women;
• sexual dysfunction and decreased physical performance;
• atrophy of the urethral mucosa, urinary incontinence, increased risk of urinary tract infections;
• lipid metabolism disorders and decreased bone mineral density – with the development of osteopenia and osteoporosis in women and an increased risk of scoliosis in pubertal girls;
• predisposition to cardiovascular and neurodegenerative diseases. [ 7 ]

Diagnostics hypoestrogenism

In endocrinology and gynecology, the diagnosis of hypoestrogenism is based not only on the assessment of symptoms and anamnesis (including family history).

To objectively confirm estrogen deficiency and identify its causes, laboratory tests are performed and blood tests are taken to measure estrogen levels, prolactin, follicle-stimulating and luteinizing hormones, anti-Müllerian hormone, thyroid hormones (total triiodothyronine) and insulin levels.

Instrumental diagnostics include ultrasound of the uterus and ovaries, X-ray of the pelvic organs, MRI of the pituitary gland, etc. [ 8 ]

See also: Diagnosis of polycystic ovaries

Differential diagnosis

Differential diagnostics aim to distinguish a decrease in estrogen levels due to damage and dysfunction of the ovaries from hypoestrogenism of pituitary-hypothalamic or autoimmune origin.

Treatment hypoestrogenism

The main treatment for hypoestrogenism in women of any age is hormone replacement therapy (HRT) with conjugated estrogens. [ 9 ]

What medications are used in this case, more detailed in the materials:

• How to increase estrogen levels?
• Hormones in pills

And all the details about phytoestrogen-based products can be found in the publication – Preparations and products containing phytoestrogens

Herbal treatment can also be used: decoctions and water infusions of fenugreek seeds and creeping tribulus, hop cones, red clover flowers, sage, and wild yam (Dioscorea).

Prevention

Hypoestrogenism associated with functional insufficiency of the hypothalamic-pituitary system, genetic and autoimmune disorders cannot be prevented. And the use of the same hormonal drugs for prevention cannot be recommended to everyone, especially considering their possible side effects.

Forecast

With low estrogen levels, the prognosis for overall health and prospects for normalizing hormonal levels depend on the causes that led to hypoestrogenism.