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Notably, certain GHS can uniquely stimulate the physiologic pulsatile GH secretion observed in vivo; this in contrast to exogenous GH therapy which often leads to persistent supra-therapeutic serum levels of GH. Side effects include joint stiffness, radiculopathy, edema, and a theoretical but never-demonstrated increased risk of malignancy. GH therapy has been shown to improve lean body mass, decrease adiposity, and improve serum lipid profiles (16,17). Growth hormone (GH) offers a method of treatment that can further address body composition independent of the androgen-dependent gonadal axis. This conversion then leads to a hyper-estrogenic state that inhibits luteinizing (LH) secretion, undermining intrinsic testicular health and stifling testosterone production (3). In turn, obese men are at an increased risk for hypogonadism given that adipose tissue contains aromatase which converts testosterone to estradiol. The GHS that will be discussed include sermorelin, growth hormone-releasing peptides (GHRP)-2, GHRP-6, ibutamoren, and ipamorelin.
Together, these findings suggest a significant role for testosterone in regulating adult muscle growth in response to mechanical loading (i.e., RE). Testosterone also effects the development of bone, connective and neural tissues (Hoffman et al., 2009), leading to increased muscle strength, power, endurance, and hypertrophy in a dose-dependent manner (Sinha-Hikim et al., 2006; Kraemer et al., 2017). Follicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the granulosa cells of the ovarian follicles and corpora lutea. The effect of estrogen on the immune system is in general described as Th2 favoring, rather than suppressive, as is the case of the effect of male sex hormone – testosterone.
Increases in leptin and leptin/body fat ratio may promote earlier satiety and confer further benefit to patients seeking to alter their body composition. While the authors found that total body fat was unchanged as previously observed, the mean total body fat decreased by a non-significant 0.2 kg at 2 weeks and 0.4 kg at 8 weeks compared to baseline. When compared to baseline, both 10 and 25 mg ibutamoren doses increased the mean 24-h GH concentration by 57% and 97%, respectively. Chapman et al. assessed ibutamoren’s effects on serum levels of both GH and IGF-1 in a randomized, double-blind placebo-controlled trial.
The study’s results also emphasize the role of sermorelin as a potent GH and IGF-1 stimulator, which can yield significant increases in lean body mass. This suggests that the timing and frequency of sermorelin treatment significantly affects IGF-1 levels, with a higher frequency of administration resulting in more significant IGF-1 increases. Interestingly, the authors observed that IGF-1 levels did not significantly increase at 2 or 6 weeks of nightly treatment, while the Corpas study showed significant increases in IGF-1 with twice daily treatment. No significant correlations were observed between total body weight and sermorelin treatment, but the study did not account for concurrent fat loss and muscle gain. Consistent with this observation, in a later study examining GH-deficient rats, sermorelin therapy was shown to result in an increase in testosterone secretion (26).
Testosterone is an essential hormone for male sexual, mental, and physical development in addition to ongoing health. Gharahdaghi N, Phillips BE, Szewczyk NJ, Smith K, Wilkinson DJ and Atherton PJ (2021) Links Between Testosterone, Oestrogen, and the Growth Hormone/Insulin-Like Growth Factor Axis and Resistance Exercise Muscle Adaptations. Also, RE-induced IGF1-Akt activation phosphorylates AS160 (Akt substrate of 160 kDa) resulting in enhanced GLUT4 translocation and glucose uptake, reflecting the mediator role of IGF-1 in glycaemic control via insulin-IGF-1-Akt pathway activation in muscle (Kido et al., 2016). This implies that locally produced, autocrine/paracrine IGF-1 plays an important role in both pre- and postnatal growth. A liver-specific knockout mouse exhibited some postnatal growth reduction, but not as severe as with global IGF knockout (Baker et al., 1993; Tahimic et al., 2013). In terms of mechanisms, following release, GH binds to its receptor leading to the recruitment and phosphorylation of Janus kinase 2 (JAK2) and its most recognized downstream target, signal transducer and activator of transcription 5 (STAT5) (Jørgensen et al., 2006). RE is the most potent physiological stimulus for GH release in both men (Nicholls and Holt, 2016; Fink et al., 2017) and women (Hymer et al., 2001), but little is known about how RE alters somatotroph content and function.
During the first year, ibutamoren resulted in a significant 1.8-fold increase in 24-h mean GH levels and a 1.5-fold increase in serum IGF-1 levels. Measured outcomes included GH, IGF-1, lipids, cortisol, insulin sensitivity, body composition, physical function, and muscle strength. Nass et al. conducted a 2-year randomized, double-blind, placebo-controlled, modified-crossover trial evaluating ibutamoren’s effects on body composition (53).
However, during pregnancy this role shifts to estriol, and in postmenopausal women estrone becomes the primary form of estrogen in the body. During menopause, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Estradiol (E2) is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. The four major naturally occurring estrogens in women are estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). Synthetic and natural estrogens have been found in the environment and are referred to as xenoestrogens. Additionally, estrogens bind to and activate rapid-signaling membrane estrogen receptors (mERs), such as GPER (GPR30). Estrogen (American English) or oestrogen (Commonwealth English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics.
In addition, estradiol is dehydrogenated by 17β-hydroxysteroid dehydrogenase into the much less potent estrogen estrone. Note that in males, estrogen is also produced by the Sertoli cells when FSH binds to their FSH receptors. Estrogen levels vary through the menstrual cycle, with levels highest near the end of the follicular phase just before ovulation. Hence, both granulosa and theca cells are essential for the production of estrogen in the ovaries.citation needed This compound crosses the basal membrane into the surrounding granulosa cells, where it is converted either immediately into estrone, or into testosterone and then estradiol in an additional step. This pathway stimulates the ERK and PI3K/AKT pathways, which are known to increase cellular proliferation and affect chromatin remodelation.

Gender: Female