High level of estrogen

Levels of estrogen varies during life (Pic. 1). The amount above 220 pg/mL is considered as high level of estrogen. 

Estrogen is the primary female sex hormone as well as a medication. It is responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Estrogens also play an important role in ensuring proper function of the male reproductive tract. 

The three major naturally occurring forms of estrogen in women are estrone (E1), estradiol (E2), and estriol (E3). Another type of estrogen called estetrol (E4) is produced only during pregnancy. In males, the main biologically active estrogen is estradiol. 

Hyperestrogenism in female can be caused by ovarian tumors, genetic conditions such as aromatase excess syndrome (also known as familial hyperestrogenism), or overconsumption of exogenous sources of estrogen, including medications used in hormone replacement therapy and hormonal contraception. 

In men causes of hyperestrogenism include diseases of the adrenal cortex (situated along the perimeter of the adrenal gland), testis or medications affecting the hypothalamus-pituitary-gonadal axis (a complex set of direct influences and feedback interactions among three endocrine glands: the hypothalamus, the pituitary gland and the adrenal glands).

In both gender liver cirrhosis is another cause, though through lowered metabolism of estrogen, not oversecretion or overconsumption.

Aromatase excess syndrome (AES or AEXS), also sometimes referred to as familial hyperestrogenism or familial gynecomastia, is a rare genetic and endocrine syndrome which is characterized by an overexpression of aromatase, the enzyme responsible for the biosynthesis of the estrogen sex hormones from the androgens, in turn resulting in excessive levels of circulating estrogens and, accordingly, symptoms of hyperestrogenism. It affects both sexes, manifesting itself in males as marked or complete phenotypical feminization (the development of physical characteristics that are usually unique to the female) and in females as hyperfeminization (extremely feminine).

High levels of estrogen can lead to fertility problems and some patient are at higher risk of development of endometrial cancer (cancer of the inner layer of uterus).

Levels of estrogen are measured by special tests, in which the blood serum or saliva is used. Estrogen tests measure one of three components: estrone, estradiol, or estriol. Every component can be measured separately. Very often the estrogen is measured as a part of hormonal profile. Other hormones such as progesterone are also measured in hormonal profile.

Treatment may consist of surgery in the case of tumors, lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males.

Symptoms

Symptoms of the condition in women may consist of menstrual irregularities, amenorrhea (absence of a menstrual period in a woman of reproductive age), abnormal vaginal bleeding, and enlargement of the uterus and breasts. It may also present as isosexual precocity (precocious puberty with phenotypically-appropriate secondary sexual characteristics) in children and as hypogonadism (diminished functional activity of the gonads), and gynecomastia (enlargement of breasts in men before or arount puberty). If left untreated, hyperestrogenism may increase the risk of estrogen-sensitive cancers such as breast cancer later in life.

The symptoms of AES, in males, include heterosexual precocity (precocious puberty with phenotypically-inappropriate secondary sexual characteristics; i.e., a fully or mostly feminized appearance), severe prepubertal or peripubertal gynecomastia, high-pitched voice, sparse facial hair, hypogonadism (dysfunctional gonads), oligozoospermia (low sperm count), small testes, micropenis (an ususually small penis), advanced bone maturation, an earlier peak height velocity (an accelerated rate of growth in regards to height), and short final stature due to early epiphyseal closure. The incidence of gynecomastia appears to be 100%.

Associated diseases

Cancer

Endogenous estrogens (estrogens that originate from within an organism) and estrogen metabolites (the intermediates and products of metabolism) play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers.

Complications

• endometrail cancer
• infertility

Risk factors

• obesity
• estrogen replacement therapy 

Prevention

This condition cannot be prevented. It is possible to eliminate risk factor such as obesity by maintaining healthy lifestyle with regular exercise.

Male fertility

Estrogen especially estradiol is necessary for creating a healthy sperm. In case of high level of estrogen, sperm levels in semen may fall. 

The function of estradiol varies depending on the cells in which it is being produced. In testicular cells, estradiol is known to regulate numerous aspects of spermatogenesis (the process in which sperms are produced). Estradiol is involved in the modulation of cell communication of Sertoli cells (cell of the testicles that is part of a seminiferous tubule and helps in the process of spermatogenesis) and in the regulation of Leydig cell (cells in testicles which are producing testosterone) function.

In the efferent ductules (connect the rete testis with the initial section of the epididymis), estradiol is involved in the reabsorption of fluids, thus, affecting sperm concentration, motility and morphology. 

Any disruption in processes of sperm development or their transport to the uterus due to high levels of estrogen can lead to fertility problems. There is lower possibility of natural conception, because the sperm is no able to reach the egg inside the fallopian tube, where the fertilization occurs. 

Female fertility

Estradiol levels in female may provide useful information for the evaluation of ovarian reserve. High levels may show poor ovarian reserve (a condition of low fertility characterized by low numbers of remaining oocytes in the ovaries). With low count of oocytes, there is lower possibility to conceive naturally.

Fertility, though usually affected to one degree or another—especially in males—is not always impaired significantly enough to prevent sexual reproduction.

One of the fundamental steps to reach the success when woman have poor ovarian reserve is still related to the number of eggs obtained after hormonal stimulation by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) analogues. 

In patients defined “poor responders,” the limited number of obtained eggs remains the main problem in optimizing the live birth rates. In fact, as a result of a lower number of oocytes retrieved, there are fewer embryos to select and transfer and subsequently these patients have lower pregnancy rates per transfer and lower cumulative pregnancy rates per started cycle compared with normal responders.