Naltrexone: Upregulates LH & Testosterone Secretion

Naltrexone upregulates LH and testosterone secretion.

  • it seems to have a very interesting effect in females vs males. so it would be considered as a gender specific (due to hypothalums differences)
  1. In females studied during the early follicular phase (cycle days 1-3), naltrexone did not stimulate LH and significantly suppressed E2 (p less than 0.0003-0.0001) and FSH
  2. Naltrexone (0.50 and 1.0 mg/kg) also did not stimulate LH release in late follicular phase females (cycle days 10-12) when estradiol levels were in the peri-ovulatory range. FSH and E2 were significantly suppressed (p less than 0.01-0.05) after 1.0 mg/kg naltrexone, but not after 0.5 mg/kg naltrexone
  3. In males all doses of naltrexone significantly stimulated LH (p less than 0.003-0.0001) and T (p less than 0.001-0.0001) but not FSH. LH increased significantly above baseline within 20 to 40 min and T increased significantly within 60 min.

[1] "Naltrexone effects on pituitary and gonadal hormones in male and female rhesus monkeys."

Previous studies with naltrexone (Nalt), a "long-lasting" opioid antagonist, demonstrated a rapid increase in luteinizing hormone (LH) secretion which gradually declined, reaching baseline values after 1 hr. A second Nalt challenge, 120 min later, caused only a blunted response. This poor reaction has been shown in this study not to be due to lack of pituitary responsiveness, because LH-releasing hormone treatment revealed a normal response.

A time-response study was carried out in order to establish the refractory period length, by administering a second Nalt injection at 0 hr (immediately after the first injection) and at 2, 4, 8, 16, and 24 hr after the first bolus. Partial responsiveness could be achieved 2 and 4 hr after the first challenge. However, only after 8 hr was a full response recorded. The diurnal changes in serum LH (nadir at 18.00 hr) did not affect the response to Nalt challenge.

  • this indicates that taking multiple doses, and perhaps in a formulation that isnt instant release (allowing sharp increase and decrease in blood concentration, to enable upregulation) can be beneficial, as it taken 8 hours post first bolus to establish the same effect. thus can be considered

It is suggested that in the presence of a Nalt blockade, nonopioid systems are able to "normalize" LH blood levels. However, when Nalt blood levels have fallen sufficiently to allow the endogenous opioid system to take primary control again, then a second Nalt injection will provoke a renewed response.

  • this could possibly mean that using low dose naltrexone (4.5mg) pre-bed in a non extended release formula would be optimal as it will normalises LH blood levels (causing upregulation of opioid system due to antagonism). done every night would ensure renewed response.

(i think most are extended release, however, breaking the tablet distinguishes this effect. the low dose naltrexone philosophy states that if used in a non extended formula then there is a sharp increase and a sharp drop in concentration. lasting a few hours. this upregulates the opioid system, which then modulates immune system, and also upregulates dopaminergic-reward pathway, by potentially increasing dopaminergic receptor count and density and/or general dopaminergic transmission )

[2] "Luteinizing hormone secretion as a response to a second naltrexone administration."