hyperestrogenism, hyperestrogenic state, estrogen excess, estrogen dominance, unopposed estrogen
Elevated levels of estrogen (Pic. 1) may be a result of exogenous administration of estrogen (a substance that induces reproductive cycle) or estrogen-like substances (imitates estrogen, for example xenoestrogens), or may be a result of physiologic conditions such as pregnancy. Hyperestrogenism can be also caused by ovarian tumors or genetic conditions such as aromatase excess syndrome (also known as familial hyperestrogenism). Liver cirrhosis is another cause, though through lowered metabolism of estrogen, not excessive secretion or overconsumption of exogenous sources of estrogen like the aforementioned causes.
Signs of hyperestrogenism may include heightened levels of one or more of the estrogen sex hormones (usually estradiol and/or estrone), lowered levels of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH). The effect on LH and/or FSH is through the suppression of the hypothalamic-pituitary-gonadal axis (an important control mechanism mainly involved in the development and regulation of the reproductive system and immune system) by estrogen. Other sign may be lowered levels of androgens such as testosterone (generally only relevant to males).
Symptoms of the condition in women may consist of menstrual irregularities, amenorrhea (an absence of periods), abnormal vaginal bleeding, and enlargement of the uterus and breasts. If left untreated, hyperestrogenism may increase the risk of estrogen-sensitive cancers such as breast cancer later in life.
It may also present as isosexual precocity (precocious puberty developing in phenotypically appropriate secondary sexual characteristics) in children and as hypogonadism (a diminished functional activity of the gonads), gynecomastia (non-cancerous increase in the size of male breast tissue), feminization (hormonally induced development of female sexual characteristics), impotence, and loss of libido in males.
Aromatase excess syndrome
Aromatase excess syndrome is a rare genetic and endocrine syndrome which is characterized by an excessive expression of aromatase, the enzyme responsible for the biosynthesis of the estrogen sex hormones including estrone and estradiol from the androgens (male sex hormones), 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 feminization (with the exception of the genitalia) of observable constitution, in whom it fits the definition of a form of intersex (person born with a reproductive or sexual anatomy that doesn’t seem to fit the typical definitions of female or male), and in females as feminization.
The balance between testosterone and estrogen is important for healthy sexual development and function. When estrogen level is elevated, these two hormones are imbalanced and for that reason the sexual functions may be impacted. Higher level of estrogen causes problems with getting or maintaining the erection.
Gynecomastia is a common disorder of the endocrine system in which there is a non-cancerous increase in the size of male breast tissue. Estrogens stimulate the proliferation of the mammary ductules (a part of breasts), androgens (i.e., testosterone), on the contrary, inhibit the process. A hormonal imbalance between these factors is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen production, a decrease in androgen production, or a combination of these two factors and results in enlarged breasts.
Testicular atrophy is a medical condition in which the male testes diminish in size and may be accompanied by loss of function. This does not refer to temporary changes. Estrogens play an important role in ensuring proper function of the male reproductive tract. Increased level of estrogens causes the paucity of germ cells, vacuolation (a development of vacuoles, organelles containing water) of Sertoli cells and a reduction in the number of Leydig cells, i.e. testicular cells that are responsible for production of sperm, testosterone, and sexual development. Since the important testicular cells are affected, testes diminish in size.
Estrogen level play crucial role in spermatogenesis (sperm production process). Levels of estrogen that are too high can be detrimental to spermatogenesis due to suppression of gonadotropin (act on the ovaries and testicles) secretion and by extension testicular testosterone production.
Polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome, the most common endocrine disorder among women of reproductive age, is characterized by the coexistence (existence at the same time) of hyperandrogenism (high male sex hormones), ovulatory dysfunction, and polycystic ovaries (PCO). In PCOS, there are ovarian cysts on the ovary surface. These cysts don’t ovulate and as a result the progesterone level is low while estrogen level is elevated. The imbalance between estrogen and progesterone level occurs and progesterone cannot balance estrogen's effect on body. Insufficient progesterone signals stimulate the hypothalamus to produce more luteinizing hormone (LH) and follicle stimulating hormone (FSH), which stimulates the ovary to produce more estrogen and androgens, which in turn stimulates more follicles toward ovulation. Because the eggs do not mature and ovulate, the two final outcomes of the reproductive cycle (regular menses or pregnancy) do not occur, the condition results in irregular or absent menstrual periods and infertility.