Women and rhGH: Misconceptions abound

Type-IIx

Well-known Member
I see a lot of misconceptions about women and rhGH. Basically, very low dosages are being used in women. While this is fairly attributable to lower body mass (m^2), the dosages are WAY off for any appreciable effects from what I can tell. Women need, controlling for body mass, about triple a male dose for similar efficacy. A lot of this is related to estradiol, exogenous estrogens, and a concomitant rise in IGFBP-1.

Perimenopausal women have remarkably high GH concentrations versus their age-matched male counterparts, yet a markedly diminished GH response as reflected by serum IGF-I concentrations.

The principal negative feedback inhibitive mechanism is via estrogen-mediated increase in IGFBP-1 levels. Higher IGFBP-1 levels reduce free IGF-I availability and (endogenously) unleash GH secretion by feedback withdrawal.

From Growth Hormone in Adults: Physiological and Clinical Aspects, Second Edition (2000):
Women have greater responsiveness to provocative GH-stimulation such as GHRH & arginine, higher basal serum GH concentrations, ambulatory GH concentration, integrated GH concentration over 24 h. Perimenopausal women secrete 1.5 to 3.1 times more GH than men... mainly due to higher GH secretory burst amplitude. The differences between perimenopausal and age-matched men after overnight fasting and normal exercise is greatest in women on oral contraceptives.

rhGH-IGF-I-gender-differences-responsiveness-Plot.png
Serum concentrations of IGF-I in 21 men & 15 women in adult GHD before and after 9 mo of treatment with rhGH.

The men and women had a similar duration of GHD (about 10 years), a similar severity, and nighttime serum GH concentrations. Yet, the men had serum IGF-I levels almost twice that of the women (123 ± 73 vs. 61 ± 32 µg/L).

In response to rhGH treatment, the following parameters changed significantly more in the men than in the women:
- serum IGF-I levels
- total body fat
- abdominal fat mass
- fat mass of the upper extremities, and
- serum markers of bone metabolism

In men, but not women, significant reductions were observed in:
- total serum cholesterol
- LDL-cholesterol
- LDL/HDL ratio
- serum apolipoprotein B
- plasma activity of plasminogen activator inhibitor (PAI-1)

Whereas an increase in serum apolipoprotein a (Lp(a)) was observed in both men and women.

The increase in LBM was significant in both men and women.

In the men there was a linear relationship between rhGH dose and increase in serum IGF-I (r = 0.60, p = 0.0004) and between the increase in IGF-I and the decrease in total body fat (r = 0.65, p = 0.014). In the women, no such relationships were observed.
[2]

Dose-response for women vs men
To achieve a normalization of serum IGF-I in 60 patients with a mean age of 47 years a daily dose of 0.6IU was sufficient in men whereas 1.2 IU (or 1.8 IU) was required in the women (Jansen, Frohlich & Roelfsema, 1997)... Oral contraceptives further reduce the responsiveness in women (Eden Engstrom et al., 1998b).

Synthetic estrogens and contraceptives in women
- may reduce the rhGH dose by 50% if a woman is switched from oral estrogen to transdermal estrogen and then to reduce it by one third if the woman discontinues transdermal estrogen, suggested by D.M. Cook, W.H. Ludlam, M.B. Cook, Route of estrogen administration helps to determine growth hormone (GH) replace-ment dose in GH-deficient adults, J. Clin. Endocrinol. Metab. 84(1999) 3956–3960
- oral estrogen administration elevates IGFBP-1 concentrations, which reduce free IGF-I availability and unleash (endogenous) GH secretion by feedback withdrawal [1]
- Systemic estrogen administration does not increase hepatic IGFBP-3 production despite clearly augmenting (endogenous) GH drive [1]. This response dissociation is consitent with relative (hepatic) resistance to GH action following high-dose estradiol exposure... A third evident distinction is that only (endogenous) estrogen secretion is characteried by concomitant ovarian production of androgen and (in the luteal phase) progesterone... in this regard, combined supplementation with estrogen and a synthetic progestin elevates both GH and IGF-I concentrations (2, 33, 34, 91) [1]. However, synthetic progestins in these contexts could act via the AR or PR.
- Estrogen selectively stimulates GH secretory-burst mass and, thereby, elevates the incremental and absolute height of serum GH concentrations (16, 18, 25, 95) [1].


References
[1] Veldhuis, J. D., & Bowers, C. Y. (2003). Human GH pulsatility: An ensemble property regulated by age and gender. Journal of Endocrinological Investigation, 26(9), 799–813. doi:10.1007/bf03345229
[2] Burman, P., Johansson, A. G., Siegbahn, A., Vessby, B., & Karlsson, F. A. (1997). Growth Hormone (GH)-Deficient Men Are More Responsive to GH Replacement Therapy Than Women. The Journal of Clinical Endocrinology & Metabolism, 82(2), 550–555. doi:10.1210/jcem.82.2.3776
 
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