Indications of Estrogen or estrogen is a special type of sex hormone that is responsible for a female to the development and regulation of the female reproductive system and secondary sexual characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy

Indications Of Estrogen

The indications of estrogen are

  • Conjugated estrogen therapy is indicated in the treatment of moderate to severe vasomotor symptoms due to menopause.
  • Conjugated estrogen therapy is indicated in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
  • Conjugated estrogen therapy is indicated in the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
  • Conjugated estrogen therapy is indicated in the treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease.
  • Conjugated estrogen therapy is indicated in the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).
  • The FDA approves of estrogen for hormone replacement therapy in the treatment of symptoms of menopause. Synthetic estrogen is also available for clinical use with the purpose of having increase absorption and effectiveness by alteration of the estrogen chemical structure for topical or oral administration.
  • Synthetic steroid estrogens include Ethinyl estradiol, estradiol valerate, estropipate, conjugate esterified estrogen, and quinestrol. Ethinyl estradiol is a commonly used synthetic estrogen to prevent pregnancy as a component of the oral contraceptive pill approved by the FDA. Some nonsteroidal synthetic estrogens include dienestrol, diethylstilbestrol, benzestrol, megestrol, and hexestrol.
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Clinically, the use of estrogen includes the following FDA-approved indications

  • Primary ovarian insufficiency
  • Female hypogonadism
  • Symptoms associated with menopause including vulvovaginal atrophy, dyspareunia, hot flashes and night sweats, and prevention of osteoporosis
  • Oral contraceptive pill (OCP) to prevent pregnancy
  • Moderate acne vulgaris
  • Prostate cancer with advanced forms of metastasis

Estrogen/synthetic estrogen has the following non-FDA-approved indication for polycystic ovarian syndrome for the relief of symptoms of hyperandrogenism and amenorrhea.

Overview of actions

  • Anabolic: Increases muscle mass and strength, speed of muscle regeneration, and bone density, increased sensitivity to exercise, protection against muscle damage, stronger collagen synthesis, increases the collagen content of connective tissues, tendons, and ligaments, but also decreases the stiffness of tendons and ligaments (especially during menstruation). Decreased stiffness of tendons gives women much lower predisposition to muscle strains but soft ligaments are much more prone to injuries (ACL tears are 2-8x more common among women than men).
    • Anti-inflammatory properties
    • Mediate formation of female secondary sex characteristics
    • Accelerate metabolism
    • Increased fat storage in some body parts such as breasts, buttocks, and legs but decreased abdominal and visceral fat (androgenic obesity).[24][25][26]Estradiol also regulates energy expenditure, body weight homeostasis, and seems to have much stronger anti-obesity effects than testosterone in general.

Women tend to have lower base strength but on average have about the same increases of muscle mass in responses to resistance training as men and far faster relative increases in strength

    • Stimulate endometrial growth
    • Increase uterine growth
    • Increase vaginal lubrication
    • Thicken the vaginal wall
    • Maintenance of vessel and skin
    • Reduce bone resorption, increase bone formation
  • Protein synthesis
    • Increase hepatic production of binding proteins
  • Coagulation
    • Increase circulating level of factors 2, 7, 9, 10, plasminogen
    • Decrease antithrombin III
    • Increase platelet adhesiveness
    • Increase vWF (estrogen -> Angiotensin II -> Vasopressin)
    • Increase PAI-1 and PAI-2 also through Angiotensin II
  • Lipid
    • Increase HDL, triglyceride
    • Decrease LDL, fat deposition
  • Fluid balance
    • Salt (sodium) and water retention
    • Increase cortisol, SHBG
  • Gastrointestinal tract
    • Reduce bowel motility
    • Increase cholesterol in bile
  • Melanin
    • Increase pheomelanin, reduce eumelanin
  • Cancer
    • Support hormone-sensitive breast cancers (see section below)
  • Lung function
    • Promotes lung function by supporting alveoli (in rodents but probably in humans).
  • Uterus lining
    • Estrogen together with progesterone promotes and maintains the uterus lining in preparation for implantation of fertilized egg and maintenance of uterus function during gestation period, also upregulates oxytocin receptor in the myometrium
  • Ovulation
    • Surge in estrogen level induces the release of luteinizing hormone, which then triggers ovulation by releasing the egg from the Graafian follicle in the ovary.
  • Sexual behavior
    • Promotes sexual receptivity in estrus,[31] and induces lordosis behavior.[32] In non-human mammals, it also induces estrus (in heat) prior to ovulation, which also induces lordosis behavior. Female non-human mammals are not sexually receptive without the estrogen surge, i.e., they have no mating desire when not in estrus.
    • Regulates the stereotypical sexual receptivity behavior; this lordosis behavior is estrogen-dependent, which is regulated by the ventromedial nucleus of the hypothalamus.
    • Sex drive is dependent on androgen levels only in the presence of estrogen, but without estrogen, free testosterone level actually decreases sexual desire (instead of increases sex drive), as demonstrated for those women who have hypoactive sexual desire disorder, and the sexual desire in these women can be restored by administration of estrogen (using oral contraceptive). In non-human mammals, mating desire is triggered by estrogen surge in estrus.
    • Estrogens are responsible for the development of female secondary sexual characteristics during puberty, including breast development, widening of the hips, and female fat distribution. Conversely, androgens are responsible for pubic and body hair growth, as well as acne and axillary odor.
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Contraindications Of Estrogen

The following are contraindications for the use of natural estrogen and synthetic estrogen derivatives:

  • Estrogen hormone receptor sensitive malignancies including breast cancer, ovarian cancer, and endometrial cancers
  • Coronary arterial disease
  • History of thromboembolism or thrombophlebitis
  • History of hypercoagulable disease (Factor V Leiden syndrome, Protein C or Protein S deficiencies and metastatic disease)
  • History of ischemic stroke
  • Migraine headaches
  • Seizure disorder
  • History of dementia or neurocognitive disorders
  • Hypertension
  • Uterine leiomyomas
  • Endometriosis
  • Urinary incontinence
  • Hyperlipidemia
  • Gallbladder disease
  • Liver disease
  • History of tobacco use

References

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