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Hormonal breast enhancement or augmentation is a medical treatment pertaining to the breasts in which hormones or hormonal agents such as estrogen, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) are utilized or manipulated to produce breast enlargement in women. It is an alternative or supplement to surgical breast augmentation with breast implants or fat transfer and other means of medical breast enlargement.〔 In addition to pharmaceuticals, some herbal breast enlargement supplements contain phytoestrogens such as 8-prenylnaringenin and miroestrol and thus may be regarded as a form of hormonal breast enhancement. However, evidence of their effectiveness, as well as safety data, are lacking.〔 ==Hormonal agents and breast growth== At puberty, estrogen, but not progesterone at this time, and GH/IGF-1 are essential for mediating the development of the breasts, and are synergistic in doing so. Hormonal contraception and hormone replacement therapy (HRT) with estrogen (and/or progestogens) have been associated with increased breast growth and breast size. A trial of hormonal breast enhancement in 45 young women with very high doses (80 mg/injection) of intramuscular, bioidentical estrogen (in the form of estradiol polyphosphate, a slow-releasing estradiol prodrug) for six months found that only the women in whom an increase in IGF-1 levels occurred after four weeks (46.7% of subjects) experienced a significant increase in breast size (824.3 mm to 898.5 mm).〔〔 This is in accordance with the established fact that both estrogen and IGF-1 are essential for breast development, and when present together, are synergistic in mediating it. Administration of estrogen to women with Turner syndrome, who normally do not develop breasts due to hypogonadism, results in normal pubertal breast development. Estrogen and GH are often combined in Turner syndrome. Estrogen in combination with GH or IGF-1 has been employed safely and effectively to improve bone density in women with anorexia nervosa. Trans women who are treated with estrogen experience normal pubertal breast development similarly to the case of girls with Turner syndrome. However, they generally show a smaller final breast size in comparison to their immediate relatives (one cup size less on average).〔 This is perhaps due to the fact that most trans women do not commence HRT until adulthood, which is of relevance because GH/IGF-1 levels significantly and progressively decrease after normal adolescent puberty (from late adolescence/early adulthood and thereafter). As such, synergy of estrogen with GH/IGF-1, and by extension, maximal breast development potential, may be reduced. Systemic administration of GH or IGF-1 causes mammary hyperplasia (enlargement of the mammary glands) in animals. For example, in a study of aged female rhesus macaques, treatment with GH alone, IGF-1 alone, and the combination of GH and IGF-1 were found to produce mammary gland hyperplasia and increased mammary gland size and epithelial proliferation by 2-fold, 3- to 4-fold, and 4- to 5-fold, respectively, changes that were directly correlated with serum concentrations of GH and IGF-1. In accordance with findings on GH/IGF-1, research has found that girls with growth hormone deficiency (GHD) who are treated with GH experience accelerated breast growth and that boys with GHD treated with GH sometimes experience gynecomastia. Moreover, IGF-1 levels and activity have been found to be correlated with breast volume in the female general population.〔 Paradoxically however, women with Laron syndrome, a condition of insensitivity to GH characterized by very low serum IGF-1 concentrations, reach normal breast size, and the breasts may be large in relation to body size, in spite of GH/IGF-1 axis insufficiency. However, contradictorily, it has also been reported that breast development is "affected" in women with Laron syndrome but that the breasts can support normal lactation, and that in animal models of Laron syndrome, mammary gland development is impaired but not abolished. Certain long-acting growth hormone secretagogues, such as CJC-1295 and ibutamoren (MK-677), are capable of reliably and effectively increasing serum GH and IGF-1 concentrations in humans. Alternatively, exogenous, pharmaceutical GH and IGF-1 (as mecasermin or mecasermin rinfabate) themselves, or analogues of IGF-1 such as des(1-3)IGF-1 and IGF-1 LR3, may be employed to increase GH/IGF-1 axis function. A number of dietary supplements, including L-arginine, L-ornithine, L-lysine, acetyl-L-carnitine, and creatine, may be able to significantly increase GH levels, although evidence is mixed. Vitamin D has been found to increase IGF-1 levels in both healthy subjects and individuals with GHD, and vitamin D deficiency is associated with low IGF-1 levels. However, there is evidence that vitamin D may also potently inhibit breast growth via activation of the vitamin D receptor. Oral estrogen treatment suppresses IGF-1 production in the liver, where approximately 80% of serum IGF-1 originates from, and reduces total serum IGF-1 levels (by 15–40%, dependent on dose and type of estrogen administered), as well as increases levels of insulin-like growth factor-binding protein 1 (IGFBP1) (a carrier protein that inhibits IGF-1 binding/activity). This results in a state of functional GH resistance (as GH induces IGF-1 production and secretion in the liver to mediate most of its effects),〔 with combined oral estrogen and GH being less effective in evoking the clinical effects of GH relative to GH alone in clinical studies of individuals with hypopituitarism/GHD.〔 In contrast, treatment with combined GH and transdermal estrogen has been found not to decrease IGF-1 levels or increase IGFBP1 levels.〔 As such, estrogen administered via other routes of administration that bypass the liver, such as transdermal (in the form of estrogen patches), sublingual, intranasal, intramuscular injection, and subcutaneous injection, may be significantly more effective than oral estrogen.〔 Progesterone and non-androgenic progestins, such as dydrogesterone, do not affect serum IGF-1 levels regardless of route of administration. However, androgenic progestins, such as 19-nortestosterone derivatives like norethisterone and levonorgestrel and others like, to a lesser extent, medroxyprogesterone acetate (MPA), when taken orally, induce IGF-1 production via activation of the androgen receptor (AR) in the liver.〔 However, at the same time, androgens potently inhibit estrogen action on the breast, such as by suppressing ER expression in breast tissue, and this action would be expected to likely cancel out any benefit. In accordance, a single small clinical study found that the addition of oral MPA to estrogen in trans women undergoing sex reassignment therapy did not result in increased breast size. Diet and nutrition have been found to affect serum IGF-1 levels. Specifically, low protein intake, fasting, and malnourishment are associated with low IGF-1 levels, whereas obesity is associated with high or normal IGF-1 levels and lowered IGFBP1 and IGFBP3 levels (resulting in higher free IGF-1 concentrations). In addition, milk consumption and circulating IGF-1 levels have been found to be positively correlated. Aside from diet and nutrition, exercise has also been found to significantly increase GH levels.〔 Androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts.〔〔 At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue.〔〔 In women with complete androgen insensitivity syndrome (CAIS), who are completely insensitive to androgens and have only modest levels of estrogen (50 pg/ml), the relatively low levels of estrogen are capable of mediating significant breast development, and the breast sizes of CAIS women, on average, are in fact actually larger than those of non-CAIS women.〔 In males treated with antiandrogens, gynecomastia (enlargement of the breasts in males) and mastodynia (breast tenderness/pain) commonly occur. Antiandrogens, for instance spironolactone, are also known to cause breast enlargement and mastodynia in women. Some examples of widely-used and highly-potent antiandrogens include cyproterone acetate and bicalutamide. Cyclooxygenase-2 (COX-2) overexpression in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, indicating a strong stimulatory effect of this enzyme on the growth of the mammary glands. These effects appear to be downstream actions of increased activation of the prostaglandin EP2, EP3, and EP4 receptors, but not the EP1 receptor, in mammary gland tissue, which in turn results in the potent induction of amphiregulin expression, a critical growth factor involved in normal mammary gland development.〔〔 In addition, agonists of the epidermal growth factor receptor (EGFR), the molecular target of amphiregulin, induce COX-2 expression in mammary gland tissue, potentially resulting in a self-perpetuating cycle of growth amplification by COX-2.〔〔 This is in accordance with the fact that long-term administration of aspirin, a COX inhibitor, as well as of other COX-inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), have been found to slightly reduce the risk of breast cancer in women (it is notable here that breast growth/size and breast cancer risk are positively associated). Taken together, these findings indicate that COX-2 inhibitors, such as aspirin, ibuprofen, naproxen, paracetamol (acetaminophen), and celecoxib, may suppress growth of breast tissue.〔〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Hormonal breast enhancement」の詳細全文を読む スポンサード リンク
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