Link

Collected Links and Excerpts on the Role of Growth Hormone (GH) and Insulin-Like Growth Factor-1 (IGF-1) in Breast Development

By Aly W. | First published August 31, 2019 | Last modified January 3, 2022

Notice: This page was originally posted as a thread on Reddit and has not yet been properly or fully revised since being moved to Transfeminine Science.

Preface

This page is a collection of links and excerpts with information on the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in breast development (as well as certain other aspects of feminization, namely hip widening). It is intended that a comprehensive article will be written on this topic at some point, but in the meantime this page can provide useful information instead.

Wikipedia

Breast Development § Hormones - Wikipedia (by Aly W.)

The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin.[1] These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.[1]

At puberty, gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile manner from the hypothalamus.[2][3] GnRH induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland.[2][3] The secreted gonadotropins travel through the bloodstream to the ovaries and trigger the secretion of estrogen and progesterone in fluctuating amounts during each menstrual cycle.[2][3] Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones.[4] During prenatal development, infancy, and childhood, GH and IGF-1 levels are low, but progressively increase and reach a peak at puberty,[5] with a 1.5- to 3-fold increase in pulsatile GH secretion and a 3-fold or greater increase in serum IGF-1 levels being capable of occurring at this time.[6] In late adolescence and early adulthood, GH and IGF-1 levels significantly decrease,[7] and continue to decrease throughout the rest of life.[5] It has been found that both estrogen and GH are essential for breast development at puberty – in the absence of either, no development will take place.[8][9] Moreover, most of the role of GH in breast development has been found to be mediated by its induction of IGF-1 production and secretion, as IGF-1 administration rescues breast development in the absence of GH.[9] GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, which is the source of approximately 80% of circulating IGF-1,[10] as well as locally in the breasts.[5][11] Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue, while IGF-1, in contrast, has been found to not do this.[12][13] In addition to estrogen and GH/IGF-1 both being essential for pubertal breast development, they are synergistic in bringing it about.[8][9][14]

Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with Laron syndrome, in whom the growth hormone receptor (GHR) is defective and insensitive to GH and serum IGF-1 levels are very low, puberty, including breast development, is delayed, although full sexual maturity is always eventually reached.[15] Moreover, breast development and size are normal (albeit delayed) in spite of GH/IGF-1 axis insufficiency, and in some the breasts may actually be large in relation to body size.[15][16] The relatively large breasts in women with Laron syndrome have been suggested to be due to increased secretion of prolactin (which is known to produce breast enlargement) caused by a drift phenomenon from somatomammotrophic cells in the pituitary gland with a high GH secretion.[15][16] An animal model of Laron syndrome, the GHR knockout mouse, shows severely impaired ductal outgrowth at 11 weeks of age.[17][18][19] However, by 15 weeks, ductal development has caught up with that of normal mice and the ducts have fully distributed throughout the mammary fat pad, although the ducts remain narrower than those of wild-type mice.[17][18][19] In any case, female GHR knockout mice can lactate normally.[17][19] As such, it has been said that the phenotypes of women with Laron syndrome and GHR knockout mice are identical, with diminished body size and delayed sexual maturation accompanied by normal lactation.[17] These data indicate that very low circulating levels of IGF-1 can nonetheless allow for full pubertal breast development.[15][17]

Reddit

Comments by Aly W. in Thread “Has anyone experimented with Ibutomoren or other iGH’s?” in r/MtFHRT

I don’t recommend growth hormone (GH), insulin-like growth factor 1 (IGF-1), or growth hormone secretagogues (GHS)—drugs that increase GH and IGF-1 levels—for improving breast development or feminization in transfeminine people. They can increase body size and growth and cause other serious adverse effects. A role of these hormones in breast development or other aspects of feminization like hip widening seems unlikely at present.

Laron syndrome, or complete GH insensitivity, is an extremely rare disease in which the growth hormone receptor (GHR) is defective and hence non-functional. As a result, the body is insensitive to the GHR-mediated effects of GH, and GH-induced synthesis of IGF-1 in the liver is lost. Consequently, circulating IGF-1 levels in individuals with Laron syndrome are very low, and these individuals experience a form of severe dwarfism. There is a good deal of evidence for an essential role of IGF-1 in breast development (Wiki). However, in spite of their very low circulating levels of IGF-1, women with Laron syndrome have normal breast development and breast sizes (Photos), and their breasts have even been described as often being relatively large for their body sizes (Laron & Kauli, 2010). Findings are essentially the same for severe growth hormone deficiency (GHD), in which circulating GH is very low or absent and IGF-1 levels are very low but breast development likewise is normal (Photos). With regard to the proportionally often large breasts of women with Laron syndrome, it has been hypothesized that this may be due to them often having high prolactin levels (Laron & Kauli, 2010). This is because prolactin is known to cause reversible breast enlargement.

The reason for the normal breast development in women with Laron syndrome and growth hormone deficiency is unclear. However, the breasts are known to produce IGF-1 locally, and this may be sufficient for normal breast development. In addition, although individuals with Laron syndrome have very low circulating levels of IGF-1, their circulating IGF-1 levels are easily detectable. About 80% of circulating IGF-1 is derived from the liver in a GH-dependent fashion, with the remaining 20% of circulating IGF-1 derived from other tissues in a GH-independent manner (Camacho, 2012). This small amount of non-GH-dependent IGF-1 may have significant physiological importance. Thus, even though circulating IGF-1 levels are very low, the breasts of women with Laron syndrome and growth hormone deficiency, and by extension typical women, may nonetheless have all the IGF-1 they need to develop normally. In accordance, studies of liver-specific knockout of IGF-1 in rodents, which resulted in a 75% decrease in circulating IGF-1 levels, found that sexual maturation and lactation were not affected (Le Roith, 2001).

It is also notable that breast development and breast size do not seem to be clearly greater in gigantism and acromegaly, two disorders of very high GH and IGF-1 levels (e.g., Photos). At least not in relation to body size and proportionality. Acromegaly is when the GH exccess occurs prior to closure of the growth plates, resulting in both general bodily enlargement and very tall stature, whereas gigantism is where the GH excess occurs after closure of the growth plates, resulting only in bodily overgrowth without tall stature. I’ve searched extensively through the literature and have been able to find essentially nothing on gigantism and acromegaly in relation to breast enlargement or above-average breast size, suggesting that the breasts are indeed normal and unchanged in these conditions.

Some transfeminine people have also asked the question of whether GH or IGF-1 could be beneficial for hip widening or pelvic feminization, since they are well-known to be involved in linear and skeletal growth during puberty. However, once again, widening of the hips appears to be normal in women with Laron syndrome (e.g., Photo), and does not seem to be greater in gigantism or acromegaly—at least in relation to body size and proportionality (e.g., Photos).

Based on the findings with disorders of GH and IGF-1 deficiency like Laron syndrome and growth hormone deficiency and of disorders of GH and IGF-1 excess like gigantism and acromegaly, it seems unlikely that GH or IGF-1 would offer any benefit for transfeminine people in terms of breast development or hip widening. Moreover, as mentioned, GH and IGF-1 increase body size—with the hands and feet being among the quickest parts of the body to enlarge—and have other adverse effects, like acne, facial and body hair growth, and various health complications. Few, if any, transfeminine people would want such effects of course. As such, GH and IGF-1 cannot be considered advisable for transfeminine people. This is not to mention the fact that the relevant available drugs (e.g., GHS) online are unregulated, experimental, and not fully evaluated in terms of efficacy or safety. This is notable as it would likely be very difficult to find a clinician willing to prescribe GH or IGF-1 for such purposes. In fact, off-label prescription of GH is illegal for physicians in the United States (Wiki). So the Internet is pretty much the only way for a person to obtain such agents.

I was more or less the person who first originated the idea in the online transfeminine community that GH and IGF-1 might be important and beneficial for breast development. It seemed like a really good hypothesis initially based on theory and preclinical findings from the literature. I posted here on Reddit on the topic under a different username back in mid-2015. But then I came across more research, including findings that contradicted the notion. Most notably, the normal and even large breasts in women with Laron syndrome and growth hormone deficiency. And my complete failure to find anything showing disproportionate breast development in acromegaly or gigantism was another important contributing factor.

It does seem like GH and IGF-1 might speed things in terms of breast development. And they might have a sensitizing effect of sorts on breast development such that lower levels of estradiol are able to induce it. It’s also theoretically plausible though not proven that GH and IGF-1 might stimulate general bodily growth such that the breasts stay proportional in size to the rest of the body. But I just haven’t seen any indication at this time that final breast size or shape will truly be greater with higher GH and/or IGF-1. Some studies have found positive associations between IGF-1 levels and breast size (e.g., Jernström et al., 2005; Hartmann et al., 1998). But these findings are just correlations and causation of course can’t be inferred. Other findings, like those described for Laron syndrome and growth hormone deficiency, as well as acromegaly and gigantism, seem to strongly contradict the notion that GH and IGF-1 are important or essential for breast development or that they could be used to improve it.

Other Reddit Comments and Threads