Estrogen and selective estrogen receptor modulators (SERMs) for the treatment of acromegaly: a meta-analysis of published observational studies

  title={Estrogen and selective estrogen receptor modulators (SERMs) for the treatment of acromegaly: a meta-analysis of published observational studies},
  author={Jennifer C. Stone and Justin Clark and Ross C. Cuneo and Anthony W. Russell and Suhail A. R. Doi},
Estrogen and selective estrogen receptor modulator (SERM) treatments for acromegaly have received limited attention since the development of newer pharmacologic therapies. There has been ongoing research evidence suggesting their utility in the biochemical control of acromegaly. Therefore, the aim of this meta-analysis was to synthesise current evidence with a view to determining to what extent and in which acromegalic patient subsets do estrogen and SERMs reduce IGF-1 levels. A literature… 

Estrogens and selective estrogen receptor modulators in acromegaly

The effect of estrogens and also of selective estrogen receptor modulators on IGF-1 control was reviewed, and proved to be an ancillary tool in the management of acromegaly.

Clomiphene citrate for treatment of acromegaly not controlled by conventional therapies.

Addition of CC should be considered an option in male acromegaly patients not controlled by current available options, with a considerable cost-saving benefit, and improvement of T levels can be obtained in those patients with concurrent central hypogonadism.

A prospective study on the efficacy of oral estrogen in female patients with acromegaly

Oral estrogen was well tolerated, but the somatotropinoma that presented ER-α expression was the only somatotropic cancer that presented growth during treatment, and a trial with oral estrogen can be an option for young women.

Aromatase enzyme expression in acromegaly and its possible relationship with disease prognosis

In patients with acromegaly and prolactinoma, aromatase expression was negatively correlated with Ki-67 score, and also it was higher in patients with complete postoperative remission than without remission, suggesting aromat enzyme expression may be a good prognostic marker predominantly in acromEGaly.

Biochemical following-up of treated acromegaly. Limitations of the current determinations of IGF-I and perspective.

  • M. Granada
  • Medicine, Biology
    Minerva endocrinologica
  • 2019
Clinical guidelines related to the diagnosis and management of patients with acromegaly state that "normal" IGF-I concentrations, (within an established age- and sex- reference range), excludes the diagnosis of active acromEGaly, and mean disease control in patients who have received treatment.


This Primer by Colao and colleagues reviews the pathogenesis, diagnosis and management of acromegaly and discusses the quality of life of patients and future outlooks.

New and emerging pharmacological treatment options for acromegaly

The development of new drugs as well as the establishment of biomarkers of disease control to allow precision medicine will improve treatment and outcomes in acromegaly.


  • Hiba Masri-IraqiA. AkirovI. Shimon
  • Medicine, Biology
    Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
  • 2020
Active acromegaly can be controlled medically in most patients, with a low rate of adverse effects, in a large cohort of patients.

Estrogen Receptors in Nonfunctioning Pituitary Neuroendocrine Tumors: Review on Expression and Gonadotroph Functions

The role of estrogen receptors in nonfunctioning pituitary neuroendocrine tumors (NF-Pitnets), focusing on immunoexpression and gonadotroph cell proliferation and apoptosis, is summarized and ERα can be a potential biomarker for predicting tumor size and invasiveness as well as therapeutic target for NF-PITnets.

Pregnancy in acromegaly is safe and is associated with improvements in IGF-1 concentrations.

The data suggests that pregnancy in women with acromegaly is generally safe, from a maternal and foetal perspective, and biochemical control tends to improve despite the withdrawal of somatostatin analogue therapy during pregnancy.



Estrogen treatment for acromegaly

Adding estrogen treatment to their ongoing medical treatment, suppressed IGF-1 significantly in all patients, achieving hormonal remission in three of them, and could be an alternative, inexpensive adjuvant treatment for females with active acromegaly.

Raloxifene lowers IGF-I levels in acromegalic women.

RAL decreases IGF-I levels in most acromegalic women with mild or intermediate disease and normalizes it in many and a prospective randomized study in patients resistant or partially sensitive to other medical treatments is warranted.

Raloxifene decreases serum IGF-I in male patients with active acromegaly.

Raloxifene might be useful in the treatment of male patients with active acromegaly, but longer term studies are clearly needed.

Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women.

E2 and raloxifene exert different hepatic endocrine, but not lipid oxidative, effects and the greater effects seen in GHD women may be explained by the loss of endogenous GH feedback.

Effects of tamoxifen on GH and IGF-I levels in acromegaly

Tamoxifen (TAM), a non steroid partially competitive antagonist to the estrogen receptors, has been reported to decrease plasma GH and IGF-I levels both in vitro and in vivo, and it is likely that the observed decrease in plasma IGF- I levels is dependent on TAM activity at the hepatic level.

Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators.

GH secretion was blunted by tamoxifen in women in the face of reduced IGF-I feedback inhibition but not in men in whom the gonadal axis was stimulated, concluding that potential blunting of GH secretion in men by SERMs was counteracted by concomitant central stimulation ofGH secretion by testosterone.

A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly.

Clinicians treating acromegalic patients should aim for random serum GH <2.5 microg/l measured by RIA and normal serum IGF-I values, to restore the elevated mortality of the condition to normal levels.

Effects of oral versus transdermal estrogen on the growth hormone/insulin-like growth factor I axis in younger and older postmenopausal women: a clinical research center study.

In postmenopausal women, oral and transdermal estrogens exert differing effects on the GH/IGF-I axis, but neither form of estrogen completely reverses the known age-related reductions in spontaneous or GHRH-stimulated GH and IGF-I.

Estroprogestinic pill normalizes IGF-I levels in acromegalic women

A pilot study shows a marked IGF-I lowering effect of pill in acromegalic women, and warrants a prospective randomized study in patients resistant or partially sensitive to other medical treatments.

Oral estroprogestin: an alternative low cost therapy for women with postoperative persistent acromegaly?

Oral estrogen treatment appears to normalize serum IGF-1 concentrations in over 70% of women with acromegaly uncured by surgery irrespective of their sensitivity to octreotide LAR, and it is suggested that estrogens may be a temporary cost-effective and safe treatment for women with postoperative persistent acromEGaly.