The estrogen insensitivity syndrome (EIS) or estrogen resistance is a form of congenital estrogen deficiency^[1] caused by a defective estrogen receptor(ER). Thus, estrogens cannot be recognized and initiate their biological action.^[2]

In humans, the condition is very rare and only one case has been described. A reported male with EIS was tall as estrogens were unable to act to close theepiphyseal line, at risk for osteoporosis, and sterile (suggesting that in humans estrogens are necessary for reproduction).^[3]

ERKO mice

Estrogen insensitivity syndrome of can be experimentally induced in animals, typically mice, by knocking out the estrogen receptor. In so-called ERKO mice different estrogens receptors can be disabled allowing to study the role of such receptors.^[4] ERKO mice show development of the respective female or male reproductive systems, and male and female alpha ERKO mice are infertile, beta ERKO males are fertile while females are subfertile, male and female double alpha and beta ERKO mice are sterile. The hypoplastic uterus does not respond to exogenous stimulation by estrogens. Males are infertile with atrophy in the testes. Bones age is delayed and bones are more brittle. Variations in these patterns can be achieved by selectively disabling the alpha or beta ERs.

AIS

In contrast to EIS, the androgen insensitivity syndrome (AIS) where the androgen receptor is defective is relatively common. This can be explained by the genetics of each syndrome. AIS is a X-linked recessive condition and thus carried over into future generations. EIS is not compatible with reproduction, thus each occurrence in humans would have to be a de-novo mutation and is not transmitted to offspring.

Congenital estrogen deficiency can also be caused by a defect in the aromatizing enzyme.

Tyler: Here’s a study I found that might be related.

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

“Estrogen exerts important effects in the skeleton, which are primarily mediated via estrogen receptor (ER)α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Previous studies demonstrate that ERα ligands might act as agonists, partial agonists, or antagonists. ERα antagonist ICI 182,780 (ICI) acts in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. Importantly, ICI exerted a pronounced inverse agonistic activity in the growth plate of mice lacking ERαAF-2. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. ”

So can ICI increase height?

“The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. ”

So if you’re estrogen insensitive such that you lack AF-2 ICI(an ERalpha agonsit) can help you grow taller.

“the ICI–ERα complex is unstable, resulting in accelerated degradation of the ERα protein”

“ICI is used as an adjuvant endocrine therapy to treat ER-positive metastatic breast cancers in postmenopausal women with disease progression following the first line of antiestrogen therapy, as tamoxifen-as well as aromatase-resistant tumors might remain sensitive to ICI treatment”

“E2 reduced both the thymus weight (–73%) and the bone-marrow cellularity (–52%) in WT mice,whereas no effect of ICI was observed on these two parameters in WT or ERαAF-20 mice”

“The increase in growth plate height by ICI in the ovx ERαAF-20 mice resulted in an increased tibia and femur length (+4.2% and +2.8%, respectively) and was specific to the appendicular
skeleton, as neither the crown-rump length (axial skeleton) nor the total body weight was altered”

The increase in height by ICI was not due to altered IGF-1 levels.

ICI resulted in a slight, not statistically significant increase in femur and tibia length in wild type mice.

But some Estrogen receptors are constitutively active even when not binding so even if you don’t have estrogen, the estrogen receptors still decrease your height thus highlighting the purpose of inhibiting the estrogen receptors themselves with something like ICI.