Jump to content

Hormonal breast enhancement

Add links
From Wikipedia, the free encyclopedia

Hormonal breast enhancement or augmentation is a highly experimental potential medical treatment for the breasts in which hormones or hormonal agents such as estrogen, progesterone, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) are utilized or manipulated to produce breast enlargement in women.[1][2] It is a possible alternative or supplement to surgical breast augmentation with breast implants or fat transfer and other means of medical breast enlargement.[2]

In addition to pharmaceuticals, some herbal breast enlargement supplements contain phytoestrogens such as 8-prenylnaringenin (found in hops) and miroestrol (a constituent of Pueraria mirifica) and thus may be regarded as a form of hormonal breast enhancement.[3] However, evidence of their effectiveness, as well as safety data, are lacking.[3]

Breast growth

[edit]
See also: Breast development § Biochemistry

At puberty, estrogen, but not progesterone at this time, and GH/IGF-1 are critical in mediating the development of the breasts, and are synergistic in doing so.[4][5][6][7][8] In accordance, hormonal contraception and hormone replacement therapy (HRT) with estrogen (and/or progestogens) have been associated with increased breast growth and breast size.[9][10] Moreover, 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).[1][2] This is in accordance with the established fact that both estrogen and IGF-1 appear to be essential for breast development, and when present together, are synergistic in mediating it.[11][12]

The administration of estrogen to women with Turner syndrome, who normally do not develop breasts due to hypogonadism, results in normal pubertal breast development.[13] Estrogen and GH are often combined in Turner syndrome.[14][15] Estrogen in combination with GH or IGF-1 has been employed safely and effectively to improve bone density in women with anorexia nervosa.[16][17][18] Trans women who are treated with estrogen experience normal pubertal breast development similarly to the case of girls with Turner syndrome.[19] However, they generally show a smaller final breast size in comparison to their immediate relatives (one cup size less on average).[19] 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).[20] 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.[21] 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.[22][23][24] Accordingly, research has found that girls with growth hormone deficiency (GHD) who are treated with GH experience accelerated breast growth[25] and that boys with growth hormone deficiency treated with GH sometimes experience gynecomastia.[26] Moreover, IGF-1 levels and activity have been found to be correlated with breast volume in the female general population.[10]

In women with Laron syndrome, where 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.[27] 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 (which has been hypothesized to be due to increased secretion of prolactin caused by a drift phenomenon from somatomammotrophic cells in the pituitary gland with a high GH secretion).[27][28] An animal model of Laron syndrome, the GHR knockout mouse, shows severely impaired ductal outgrowth at 11 weeks of age.[29][30][31] 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.[29][30][31] In any case, female GHR knockout mice can lactate normally.[29][31] As such, taken together, it is 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.[29]

An adolescent Vietnamese girl with Laron syndrome who was treated with a high dosage of IGF-1 and a gonadotropin-releasing hormone analogue for 3–4 years paradoxically experienced isolated progression of breast development without any other pubertal changes in spite of estrogen levels in the low prepubertal range.[32] Noting that gynecomastia is a recognized complication of treatment with GH and IGF-1, the authors of the study attributed the breast development to a synergism of her high, supraphysiological IGF-1 levels with the low levels of estrogen derived from peripheral aromatization of adrenal androgens.[32]

Certain long-acting growth hormone secretagogues, such as CJC-1295[33] and ibutamoren (MK-677),[34] are capable of reliably and effectively increasing serum GH and IGF-1 concentrations in humans.[35][36][37] 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.[38][39][40][41][42] 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.[43][44][45] However, there is evidence that vitamin D may also potently inhibit breast growth via activation of the vitamin D receptor.[46][47][48][49]

Oral estrogen treatment suppresses IGF-1 production in the liver, where approximately 80% of serum IGF-1 originates from,[50] 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).[51] 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),[50] 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.[51] In contrast, treatment with combined GH and transdermal estrogen has been found not to decrease IGF-1 levels or increase IGFBP1 levels.[51] 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.[51]

Progesterone and non-androgenic progestins, such as dydrogesterone, do not affect serum IGF-1 levels regardless of route of administration.[52] 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.[52] 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.[53][54] 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.[55]

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).[56][57][58] In addition, milk consumption and circulating IGF-1 levels have been found to be positively correlated.[59] Aside from diet and nutrition, exercise has also been found to significantly increase GH levels.[38]

Androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts.[53][54][60][61] At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue.[53][54] 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.[60] In males treated with antiandrogens, gynecomastia (enlargement of the breasts in males) and mastodynia (breast tenderness/pain) commonly occur.[62][63][64] Antiandrogens, for instance spironolactone, are also known to cause breast enlargement and mastodynia in women.[65] Some examples of widely used and highly-potent antiandrogens include cyproterone acetate and bicalutamide.[66][67]

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.[68][69] 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.[68][69] 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.[68][69] This mechanism is closely related to formation, growth, and spreading of cancers with poor prognosis, and is in accordance with the fact that long-term administration of aspirin, a COX inhibitor, as well as of other COX-inhibiting nonsteroidal 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).[70] Taken together, these findings indicate that COX-2 inhibitors, such as aspirin, ibuprofen, naproxen, and celecoxib, may decrease breast cell proliferation.[68][69]

Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size.[71] Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter.[71] A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferation of breast epithelial tissue caused by exposure to macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia.[71] As such, treatment with HGF or agonists of its receptor, c-Met, or potentiators of the HGF-c-Met axis (such as dihexa)[72] might have the potential to induce macromastia-like breast growth in an exposure-dependent manner.[71]

Possible increased risk of cancer

[edit]
See also: IGF-1 receptor § Role in cancer

The risk of breast cancer in women is approximately 100-fold that of men.[73] As such, the development of female-typical breasts is associated with a dramatic increase in the risk of breast cancer.[73] Moreover, breast size and breast cancer are positively correlated,[74][75] and macromastia, a condition of excessively large breast size, is considered to be a risk factor for breast cancer.[citation needed] In accordance, it has been hypothesized that there could be a further increase in the risk of breast cancer with hormonal breast enhancement.[2]

Long-term treatment with estrogens and/or progestogens in women, specifically in the form of oral contraceptives, appears to be associated with a slightly increased risk of breast cancer.[76][77] The risk appears to be highest in younger women, notably in those who started taking oral contraceptives before 20 years of age.[78] This could be related to increased synergy of estrogens with the higher levels of GH/IGF-1 that are present with younger age.[79]

Research has suggested that the enhancement of growth factor pathways, including that of GH/IGF-1, could potentially increase the risk of various cancers, including breast cancer.[80] Increased proliferation due to increased IGF-1 activity has been suggested to possibly play a key role in the high risk of breast cancer seen in women with the BRCA1 mutation.[81] Multiple large studies have found a correlation in premenopausal women between serum IGF-1 levels in the upper quartile of the normal range and IGFBP-3 levels in the lower quartile (i.e., high circulating IGF-1 levels and low circulating IFGBP-3 levels) and the risk of developing various cancers, including breast cancer.[82][83] However, the increase in breast cancer risk has been found only to be modest (e.g., only more than twice the usual risk).[84] Subsequent studies have found the increase in risk to be even less clear, and it is notable that high-normal range IGF-1 levels have been found to correlate only with premenopausal and not with postmenopausal breast cancer incidence.[85][86] In any case, mice engineered to have lower circulating levels of IGF-1 show a lower risk of developing various cancers, including breast cancer.[87] In contrast to the case of IGF-1, the upper quintile (20%) of postmenopausal women with the highest of both circulating estrogen and androgen levels have been found to have a significantly increased risk of breast cancer (relative to lowest quintile, the risk is 2- to 3-fold higher).[86] A significant positive association with breast cancer risk has also been found with prolactin levels in postmenopausal women.[86]

In acromegaly, a condition caused and maintained by highly elevated GH/IGF-1 levels, overall, there appears to be little or no increased risk of breast cancer nor certain other cancers (e.g., prostate cancer, lung cancer) relative to that of the general population.[88][89] That said, cancer risk does appear to be consistently elevated in individuals specifically with uncontrolled disease.[90] In addition, there appears to be an increased risk of colorectal cancer and pre-malignant tubular adenomas in acromegaly.[91] In any case, individuals with acromegaly appear to show no increased risk of cancer mortality or general mortality post-treatment (i.e., after their GH/IGF-1 levels have been normalized with medical treatment), and this includes breast cancer.[27][89][92] (Larger-scale studies may be needed, however.)[89][91] In contrast to acromegaly, people with Laron syndrome, a condition characterized by insensitivity to GH and very low IGF-1 levels, have a majorly reduced, in fact almost absent, risk of developing cancer, including breast cancer.[93] There has been concern expressed about doping in athletes with GH/IGF-1 and possible increased risk of cancer, including breast cancer.[94]

See also

[edit]

References

[edit]
  1. ^ a b R.E. Mansel; Oystein Fodstad; Wen G. Jiang (14 June 2007). Metastasis of Breast Cancer. Springer Science & Business Media. pp. 217–. ISBN 978-1-4020-5866-0.
  2. ^ a b c d Hartmann BW, Laml T, Kirchengast S, Albrecht AE, Huber JC (1998). "Hormonal breast augmentation: prognostic relevance of insulin-like growth factor-I". Gynecol. Endocrinol. 12 (2): 123–7. doi:10.3109/09513599809024960. PMID 9610425.
  3. ^ a b Fugh-Berman A (2003). ""Bust enhancing" herbal products". Obstet. Gynecol. 101 (6): 1345–9. doi:10.1016/s0029-7844(03)00362-4. PMID 12798545.
  4. ^ Brisken; Malley (December 2, 2010). "Hormone Action in the Mammary Gland". Cold Spring Harb. Perspect. Biol. 2 (12). Cold Spring Harb Perspect Biol: a003178. doi:10.1101/cshperspect.a003178. PMC 2982168. PMID 20739412.
  5. ^ Kleinberg DL (1998). "Role of IGF-I in normal mammary development". Breast Cancer Res. Treat. 47 (3): 201–8. doi:10.1023/a:1005998832636. PMID 9516076.
  6. ^ Kleinberg DL (1997). "Early mammary development: growth hormone and IGF-1". J Mammary Gland Biol Neoplasia. 2 (1): 49–57. doi:10.1023/a:1026373513521. PMID 10887519.
  7. ^ Ruan W, Kleinberg DL (1999). "Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development". Endocrinology. 140 (11): 5075–81. doi:10.1210/endo.140.11.7095. PMID 10537134.
  8. ^ Kleinberg DL, Feldman M, Ruan W (2000). "IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis". J Mammary Gland Biol Neoplasia. 5 (1): 7–17. doi:10.1023/a:1009507030633. PMID 10791764.
  9. ^ Isaksson, Erika; Sahlin, Lena; Söderqvist, Gunnar; von Schoultz, Eva; Masironi, Britt; Wickman, Marie; Wilking, Nils; von Schoultz, Bo; Skoog, Lambert (1999). "Expression of sex steroid receptors and IGF-1 mRNA in breast tissue — effects of hormonal treatment". J. Steroid Biochem. Mol. Biol. 70 (4–6): 257–262. doi:10.1016/S0960-0760(99)00115-6. ISSN 0960-0760. PMID 10622416.
  10. ^ a b Jernström, H; Sandberg, T; Bågeman, E; Borg, Å; Olsson, H (2005). "Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families". Br. J. Cancer. 92 (5): 857–866. doi:10.1038/sj.bjc.6602389. ISSN 0007-0920. PMC 2361904. PMID 15756256.
  11. ^ Derek Leroith; Walter Zumkeller; Robert C. Baxter (31 July 2003). Insulin-like Growth Factor Receptor Signalling. Springer Science & Business Media. pp. 189–. ISBN 978-0-306-47846-8.
  12. ^ Kleinberg, David L.; Ruan, Weifeng (2008). "IGF-I, GH, and Sex Steroid Effects in Normal Mammary Gland Development". J. Mammary Gland Biol. Neoplasia. 13 (4): 353–360. doi:10.1007/s10911-008-9103-7. ISSN 1083-3021. PMID 19034633.
  13. ^ Ismail Jatoi; Manfred Kaufmann (11 February 2010). Management of Breast Diseases. Springer Science & Business Media. pp. 19–. ISBN 978-3-540-69743-5.
  14. ^ Suzanne B. Cassidy; Judith E. Allanson (20 September 2011). Management of Genetic Syndromes. John Wiley & Sons. pp. 1330–. ISBN 978-1-118-21067-3.
  15. ^ Gonzalez L, Witchel SF (2012). "The patient with Turner syndrome: puberty and medical management concerns". Fertil. Steril. 98 (4): 780–6. doi:10.1016/j.fertnstert.2012.07.1104. PMC 3760009. PMID 22884020.
  16. ^ Misra M, Klibanski A (2014). "Endocrine consequences of anorexia nervosa". Lancet Diabetes Endocrinol. 2 (7): 581–92. doi:10.1016/S2213-8587(13)70180-3. PMC 4133106. PMID 24731664.
  17. ^ Grinspoon S, Miller K, Herzog D, Clemmons D, Klibanski A (2003). "Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: a randomized-controlled study". J. Clin. Endocrinol. Metab. 88 (3): 1142–9. doi:10.1210/jc.2002-021402. PMID 12629097.
  18. ^ Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A (2002). "Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa". J. Clin. Endocrinol. Metab. 87 (6): 2883–91. doi:10.1210/jcem.87.6.8574. PMID 12050268.
  19. ^ a b James Barrett (2007). Transsexual and Other Disorders of Gender Identity: A Practical Guide to Management. Radcliffe Publishing. pp. 172–. ISBN 978-1-85775-719-4.
  20. ^ Chong YM, Subramanian A, Sharma AK, Mokbel K (2007). "The potential clinical applications of insulin-like growth factor-1 ligand in human breast cancer". Anticancer Res. 27 (3B): 1617–24. PMID 17595785.
  21. ^ Kleinberg DL, Wood TL, Furth PA, Lee AV (2009). "Growth hormone and insulin-like growth factor-I in the transition from normal mammary development to preneoplastic mammary lesions". Endocr. Rev. 30 (1): 51–74. doi:10.1210/er.2008-0022. PMC 5393153. PMID 19075184.
  22. ^ Alice C. Levine (3 October 2011). Hormones and Cancer: Breast and Prostate, An Issue of Endocrinology and Metabolism Clinics of North America. Elsevier Health Sciences. pp. 26–. ISBN 978-1-4557-1239-7.
  23. ^ Douglas Yee (2004). Insulin-like Growth Factors. IOS Press. pp. 33–. ISBN 978-1-58603-409-2.
  24. ^ Ng ST, Zhou J, Adesanya OO, Wang J, LeRoith D, Bondy CA (1997). "Growth hormone treatment induces mammary gland hyperplasia in aging primates". Nat. Med. 3 (10): 1141–4. doi:10.1038/nm1097-1141. PMID 9334728.
  25. ^ Sat Dharam Kaur (2003). The Complete Natural Medicine Guide to Breast Cancer: A Practical Manual for Understanding, Prevention & Care. R. Rose. p. 79. ISBN 978-0-7788-0083-5.
  26. ^ Souza, Flavio Moutinho; Collett-Solberg, Paulo Ferrez (2011). "Adverse effects of growth hormone replacement therapy in children". Arq. Bras. Endocrinol. Metab. 55 (8): 559–565. doi:10.1590/S0004-27302011000800009. ISSN 0004-2730. PMID 22218437.
  27. ^ a b c Zvi Laron; J. Kopchick (25 November 2010). Laron Syndrome - From Man to Mouse: Lessons from Clinical and Experimental Experience. Springer Science & Business Media. pp. 113, 498. ISBN 978-3-642-11183-9.
  28. ^ Laron, Zvi (2004). "Laron Syndrome (Primary Growth Hormone Resistance or Insensitivity): The Personal Experience 1958–2003". J. Clin. Endocrinol. Metab. 89 (3): 1031–1044. doi:10.1210/jc.2003-031033. ISSN 0021-972X. PMID 15001582.
  29. ^ a b c d Brisken, Cathrin (2002). "Hormonal Control of Alveolar Development and Its Implications for Breast Carcinogenesis". J. Mammary Gland Biol. Neoplasia. 7 (1): 39–48. doi:10.1023/A:1015718406329. ISSN 1083-3021. PMID 12160085.
  30. ^ a b McNally, Sara; Martin, Finian (2011). "Molecular regulators of pubertal mammary gland development". Ann. Med. 43 (3): 212–234. doi:10.3109/07853890.2011.554425. ISSN 0785-3890.
  31. ^ a b c Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, Okada S, Cataldo L, Coschigamo K, Wagner TE, Baumann G, Kopchick JJ (1997). "A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)". Proc. Natl. Acad. Sci. U.S.A. 94 (24): 13215–20. Bibcode:1997PNAS...9413215Z. doi:10.1073/pnas.94.24.13215. PMC 24289. PMID 9371826.
  32. ^ a b Walker, J. L.; Crock, P. A.; Behncken, S. N.; Rowlinson, S. W.; Nicholson, L. M.; Boulton, T. J. C.; Waters, M. J. (1998). "A Novel Mutation Affecting the Interdomain Link Region of the Growth Hormone Receptor in a Vietnamese Girl, and Response to Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor-I and Luteinizing Hormone-Releasing Hormone Analogue1". J. Clin. Endocrinol. Metab. 83 (7): 2554–2561. doi:10.1210/jcem.83.7.4954. ISSN 0021-972X. PMID 9661642.
  33. ^ Teichman, Sam L.; Neale, Ann; Lawrence, Betty; Gagnon, Catherine; Castaigne, Jean-Paul; Frohman, Lawrence A. (2006). "Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults". J. Clin. Endocrinol. Metab. 91 (3): 799–805. doi:10.1210/jc.2005-1536. ISSN 0021-972X. PMID 16352683.
  34. ^ Copinschi, G; Van Onderbergen, A; L'Hermite-Balériaux, M; Mendel, C M; Caufriez, A; Leproult, R; Bolognese, J A; De Smet, M; Thorner, M O; Van Cauter, E (1996). "Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men". J. Clin. Endocrinol. Metab. 81 (8): 2776–2782. doi:10.1210/jcem.81.8.8768828. ISSN 0021-972X. PMID 8768828.
  35. ^ Cruz CR, Smith RG (2008). "The growth hormone secretagogue receptor". Vitam. Horm. Vitamins & Hormones. 77: 47–88. doi:10.1016/S0083-6729(06)77004-2. ISBN 978-0-12-373685-7. PMID 17983853.
  36. ^ Lengyel AM (2006). "Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin". Braz. J. Med. Biol. Res. 39 (8): 1003–11. doi:10.1590/s0100-879x2006000800002. PMID 16906274.
  37. ^ Arvat E, Gianotti L, Giordano R, Broglio F, Maccario M, Lanfranco F, Muccioli G, Papotti M, Graziani A, Ghigo E, Deghenghi R (2001). "Growth hormone-releasing hormone and growth hormone secretagogue-receptor ligands: focus on reproductive system". Endocrine. 14 (1): 35–43. doi:10.1385/endo:14:1:035. PMID 11322500.
  38. ^ a b Marie Dunford; J. Doyle (3 February 2014). Nutrition for Sport and Exercise. Cengage Learning. pp. 190–. ISBN 978-1-285-75249-5.
  39. ^ Ira Wolinsky; Judy A. Driskell (25 June 2004). Nutritional Ergogenic Aids. CRC Press. pp. 27–28. ISBN 978-0-203-50770-4.
  40. ^ Fred Brouns; Cerestar-Cargill (7 February 2003). Essentials of Sports Nutrition. John Wiley & Sons. pp. 141–. ISBN 978-0-470-85536-2.
  41. ^ Joseph F. Audette; Allison Bailey (26 February 2008). Integrative Pain Medicine: The Science and Practice of Complementary and Alternative Medicine in Pain Management. Springer Science & Business Media. pp. 159–. ISBN 978-1-59745-344-8.
  42. ^ Schedel JM, Tanaka H, Kiyonaga A, Shindo M, Schutz Y (2000). "Acute creatine loading enhances human growth hormone secretion". J. Sports Med. Phys. Fit. 40 (4): 336–42. PMID 11297004.
  43. ^ Ameri P, Giusti A, Boschetti M, Bovio M, Teti C, Leoncini G, Ferone D, Murialdo G, Minuto F (2013). "Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency". Eur. J. Endocrinol. 169 (6): 767–72. doi:10.1530/EJE-13-0510. PMID 24005315.
  44. ^ Ameri P, Giusti A, Boschetti M, Murialdo G, Minuto F, Ferone D (2013). "Interactions between vitamin D and IGF-I: from physiology to clinical practice". Clin. Endocrinol. 79 (4): 457–63. doi:10.1111/cen.12268. PMID 23789983.
  45. ^ Bogazzi F, Rossi G, Lombardi M, Tomisti L, Sardella C, Manetti L, Curzio O, Marcocci C, Grasso L, Gasperi M, Martino E (2011). "Vitamin D status may contribute to serum insulin-like growth factor I concentrations in healthy subjects". J. Endocrinol. Investig. 34 (8): e200–3. doi:10.3275/7228. PMID 20671418.
  46. ^ Wanda M. Haschek; Colin G. Rousseaux; Matthew A. Wallig (1 May 2013). Haschek and Rousseaux's Handbook of Toxicologic Pathology. Elsevier Science. pp. 2675–. ISBN 978-0-12-415765-1.
  47. ^ Lopes N, Paredes J, Costa JL, Ylstra B, Schmitt F (2012). "Vitamin D and the mammary gland: a review on its role in normal development and breast cancer". Breast Cancer Res. 14 (3): 211. doi:10.1186/bcr3178. PMC 3446331. PMID 22676419.
  48. ^ Welsh J (2007). "Targets of vitamin D receptor signaling in the mammary gland". J. Bone Miner. Res. 22 Suppl 2: V86–90. doi:10.1359/jbmr.07s204. PMID 18290729.
  49. ^ Welsh J (2011). "Vitamin D metabolism in mammary gland and breast cancer". Mol. Cell. Endocrinol. 347 (1–2): 55–60. doi:10.1016/j.mce.2011.05.020. PMID 21669251.
  50. ^ a b Pauline M. Camacho (26 September 2012). Evidence-Based Endocrinology. Lippincott Williams & Wilkins. pp. 20–. ISBN 978-1-4511-7146-4.
  51. ^ a b c d Isotton, A. L.; Wender, M. C. O.; Casagrande, A.; Rollin, G.; Czepielewski, M. A. (2011). "Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study" (PDF). Eur. J. Endocrinol. 166 (2): 207–213. doi:10.1530/EJE-11-0560. ISSN 0804-4643. PMID 22108915.
  52. ^ a b Sonnet, Emmanuel; Lacut, Karine; Roudaut, Nathalie; Mottier, Dominique; Kerlan, Véronique; Oger, Emmanuel (2007). "Effects of the route of oestrogen administration on IGF-1 and IGFBP-3 in healthy postmenopausal women: results from a randomized placebo-controlled study". Clin. Endocrinol. 66 (5): 626–631. doi:10.1111/j.1365-2265.2007.02783.x. ISSN 0300-0664. PMID 17492948.
  53. ^ a b c Jernström H, Olsson H (1997). "Breast size in relation to endogenous hormone levels, body constitution, and oral contraceptive use in healthy nulligravid women aged 19-25 years". Am. J. Epidemiol. 145 (7): 571–80. doi:10.1093/oxfordjournals.aje.a009153. PMID 9098173.
  54. ^ a b c Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA (2000). "Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression". FASEB J. 14 (12): 1725–30. doi:10.1096/fj.99-0863com. PMID 10973921.
  55. ^ Meyer WJ, Webb A, Stuart CA, Finkelstein JW, Lawrence B, Walker PA (1986). "Physical and hormonal evaluation of transsexual patients: a longitudinal study". Arch. Sex. Behav. 15 (2): 121–38. doi:10.1007/bf01542220. PMID 3013122.
  56. ^ Lawrence F. Ditmier (1 January 2006). New Developments in Obesity Research. Nova Publishers. pp. 20–21. ISBN 978-1-60021-296-3.
  57. ^ Peter G. Kopelman; Ian D. Caterson; William H. Dietz (15 April 2008). Clinical Obesity in Adults and Children. John Wiley & Sons. pp. 202–. ISBN 978-1-4051-4366-0.
  58. ^ Robert H. Eckel (2003). Obesity: Mechanisms and Clinical Management. Lippincott Williams & Wilkins. pp. 157–. ISBN 978-0-7817-2844-7.
  59. ^ Qin LQ, He K, Xu JY (2009). "Milk consumption and circulating insulin-like growth factor-I level: a systematic literature review". Int. J. Food Sci. Nutr. 60 Suppl 7: 330–40. doi:10.1080/09637480903150114. PMID 19746296.
  60. ^ a b Jerome F. Strauss, III; Robert L. Barbieri (13 September 2013). Yen and Jaffe's Reproductive Endocrinology. Elsevier Health Sciences. pp. 236–. ISBN 978-1-4557-2758-2.
  61. ^ Christopher B. Wilson; Victor Nizet; Yvonne Maldonado; Jack S. Remington; Jerome O. Klein (24 February 2015). Remington and Klein's Infectious Diseases of the Fetus and Newborn Infant. Elsevier Health Sciences. pp. 190–. ISBN 978-0-323-24147-2.
  62. ^ Jeanne Held-Warmkessel (2006). Contemporary Issues in Prostate Cancer: A Nursing Perspective. Jones & Bartlett Learning. pp. 256–. ISBN 978-0-7637-3075-8.
  63. ^ Bowman JD, Kim H, Bustamante JJ (2012). "Drug-induced gynecomastia". Pharmacotherapy. 32 (12): 1123–40. doi:10.1002/phar.1138. PMID 23165798.
  64. ^ Narula HS, Carlson HE (2014). "Gynaecomastia--pathophysiology, diagnosis and treatment". Nat. Rev. Endocrinol. 10 (11): 684–98. doi:10.1038/nrendo.2014.139. PMID 25112235.
  65. ^ Jeffrey K. Aronson (2 March 2009). Meyler's Side Effects of Cardiovascular Drugs. Elsevier. pp. 255–. ISBN 978-0-08-093289-7.
  66. ^ Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1196–. ISBN 978-0-7817-1750-2.
  67. ^ Sarah H. Wakelin; Howard I. Maibach; Clive B. Archer (21 May 2015). Handbook of Systemic Drug Treatment in Dermatology, Second Edition. CRC Press. pp. 29–. ISBN 978-1-4822-2286-9.
  68. ^ a b c d Chang SH, Ai Y, Breyer RM, Lane TF, Hla T (2005). "The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia". Cancer Res. 65 (11): 4496–9. doi:10.1158/0008-5472.CAN-05-0129. PMID 15930264.
  69. ^ a b c d Al-Salihi MA, Ulmer SC, Doan T, Nelson CD, Crotty T, Prescott SM, Stafforini DM, Topham MK (2007). "Cyclooxygenase-2 transactivates the epidermal growth factor receptor through specific E-prostanoid receptors and tumor necrosis factor-alpha converting enzyme". Cell. Signal. 19 (9): 1956–63. doi:10.1016/j.cellsig.2007.05.003. PMC 2681182. PMID 17572069.
  70. ^ de Pedro M, Baeza S, Escudero MT, Dierssen-Sotos T, Gómez-Acebo I, Pollán M, Llorca J (2015). "Effect of COX-2 inhibitors and other non-steroidal inflammatory drugs on breast cancer risk: a meta-analysis". Breast Cancer Res. Treat. 149 (2): 525–36. doi:10.1007/s10549-015-3267-9. PMID 25589172.
  71. ^ a b c d Zhong, Aimei; Wang, Guohua; Yang, Jie; Xu, Qijun; Yuan, Quan; Yang, Yanqing; Xia, Yun; Guo, Ke; Horch, Raymund E.; Sun, Jiaming (2014). "Stromal-epithelial cell interactions and alteration of branching morphogenesis in macromastic mammary glands". J Cell Mol Med. 18 (7): 1257–1266. doi:10.1111/jcmm.12275. ISSN 1582-1838. PMC 4124011. PMID 24720804.
  72. ^ Benoist, C. C.; Kawas, L. H.; Zhu, M.; Tyson, K. A.; Stillmaker, L.; Appleyard, S. M.; Wright, J. W.; Wayman, G. A.; Harding, J. W. (2014). "The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System". J. Pharmacol. Exp. Ther. 351 (2): 390–402. doi:10.1124/jpet.114.218735. ISSN 1521-0103. PMC 4201273. PMID 25187433.
  73. ^ a b Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms. Elsevier Science. 1 August 2014. pp. 946–. ISBN 978-0-12-386457-4.
  74. ^ Jansen, L.A.; Backstein, R.M.; Brown, M.H. (2014). "Breast size and breast cancer: A systematic review". J. Plast. Reconstr. Aesthetic Surg. 67 (12): 1615–1623. doi:10.1016/j.bjps.2014.10.001. ISSN 1748-6815. PMID 25456291.
  75. ^ Eriksson, Nicholas; Benton, Geoffrey M; Do, Chuong B; Kiefer, Amy K; Mountain, Joanna L; Hinds, David A; Francke, Uta; Tung, Joyce Y (2012). "Genetic variants associated with breast size also influence breast cancer risk". BMC Medical Genetics. 13 (1): 53. doi:10.1186/1471-2350-13-53. ISSN 1471-2350. PMC 3483246. PMID 22747683.
  76. ^ Beaber EF, Malone KE, Tang MT, Barlow WE, Porter PL, Daling JR, Li CI (2014). "Oral contraceptives and breast cancer risk overall and by molecular subtype among young women". Cancer Epidemiol. Biomarkers Prev. 23 (5): 755–64. doi:10.1158/1055-9965.EPI-13-0944. PMC 4032363. PMID 24633144.
  77. ^ Hunter DJ, Colditz GA, Hankinson SE, Malspeis S, Spiegelman D, Chen W, Stampfer MJ, Willett WC (2010). "Oral contraceptive use and breast cancer: a prospective study of young women". Cancer Epidemiol. Biomarkers Prev. 19 (10): 2496–502. doi:10.1158/1055-9965.EPI-10-0747. PMC 3055790. PMID 20802021.
  78. ^ Monica Morrow; Virgil Craig Jordan (2003). Managing Breast Cancer Risk. PMPH-USA. pp. 50–. ISBN 978-1-55009-260-8.
  79. ^ Lukanova, A.; Toniolo, P.; Zeleniuch-Jacquotte, A.; Grankvist, K.; Wulff, M.; Arslan, A. A.; Afanasyeva, Y.; Johansson, R.; Lenner, P.; Hallmans, G.; Wadell, G.; Lundin, E. (2006). "Insulin-like Growth Factor I in Pregnancy and Maternal Risk of Breast Cancer". Cancer Epidemiol. Biomarkers Prev. 15 (12): 2489–2493. doi:10.1158/1055-9965.EPI-06-0625. ISSN 1055-9965. PMID 17132766.
  80. ^ Ibrahim YH, Yee D (2004). "Insulin-like growth factor-I and cancer risk". Growth Horm. IGF Res. 14 (4): 261–9. doi:10.1016/j.ghir.2004.01.005. PMID 15231294.
  81. ^ Barcellos-Hoff MH, Kleinberg DL (2013). "Breast cancer risk in BRCA1 mutation carriers: insight from mouse models". Ann. Oncol. 24 Suppl 8: viii8–viii12. doi:10.1093/annonc/mdt305. PMID 24131977.
  82. ^ LeRoith D, Roberts CT (2003). "The insulin-like growth factor system and cancer". Cancer Lett. 195 (2): 127–37. doi:10.1016/s0304-3835(03)00159-9. PMID 12767520.
  83. ^ Grimberg A (2003). "Mechanisms by which IGF-I may promote cancer". Cancer Biol. Ther. 2 (6): 630–5. doi:10.4161/cbt.2.6.678. PMC 4164051. PMID 14688466.
  84. ^ Fletcher O, Gibson L, Johnson N, Altmann DR, Holly JM, Ashworth A, Peto J, Silva Idos S (2005). "Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review". Cancer Epidemiol. Biomarkers Prev. 14 (1): 2–19. doi:10.1158/1055-9965.2.14.1. PMID 15668470.
  85. ^ Renehan AG, Harvie M, Howell A (2006). "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on". Endocr. Relat. Cancer. 13 (2): 273–8. doi:10.1677/erc.1.01219. PMID 16728563.
  86. ^ a b c Hankinson SE (2005). "Endogenous hormones and risk of breast cancer in postmenopausal women". Breast Dis. 24: 3–15. doi:10.3233/bd-2006-24102. PMID 16917136.
  87. ^ Yakar S, Pennisi P, Zhao H, Zhang Y, LeRoith D (2004). Circulating IGF-1 and its role in cancer: lessons from the IGF-1 gene deletion (LID) mouse. Novartis Found. Symp. Vol. 262. pp. 3–9, discussion 9–18, 265–8. doi:10.1002/0470869976.ch2. ISBN 978-0-470-86998-7. PMID 15562820. {{cite book}}: |journal= ignored (help)
  88. ^ Shim M, Cohen P (1999). "IGFs and human cancer: implications regarding the risk of growth hormone therapy". Horm. Res. 51 Suppl 3: 42–51. doi:10.1159/000053161 (inactive 2024-11-11). PMID 10592443.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  89. ^ a b c Webb SM, Casanueva F, Wass JA (2002). "Oncological complications of excess GH in acromegaly". Pituitary. 5 (1): 21–5. doi:10.1023/a:1022149300972. PMID 12638722.
  90. ^ Loeper S, Ezzat S (2008). "Acromegaly: re-thinking the cancer risk". Rev. Endocr. Metab. Disord. 9 (1): 41–58. doi:10.1007/s11154-007-9063-z. PMID 18157698.
  91. ^ a b Jenkins PJ (2004). "Acromegaly and cancer". Horm. Res. 62 Suppl 1: 108–15. doi:10.1159/000080768 (inactive 2024-11-11). PMID 15761242.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  92. ^ Nathan A. Berger (19 June 2015). Murine Models, Energy Balance, and Cancer. Springer. pp. 76–. ISBN 978-3-319-16733-6.
  93. ^ Gallagher, Emily Jane; LeRoith, Derek (2011). "Is Growth Hormone Resistance/IGF-1 Reduction Good for You?". Cell Metab. 13 (4): 355–356. doi:10.1016/j.cmet.2011.03.003. ISSN 1550-4131. PMID 21459318.
  94. ^ Tentori L, Graziani G (2007). "Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?". Pharmacol. Res. 55 (5): 359–69. doi:10.1016/j.phrs.2007.01.020. PMID 17349798.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hormonal_breast_enhancement&oldid=1258095098"