QUESTION--I saw a 8.8 year girl with early onset , rapid progressing puberty, bone age at 11.9 years, A+B2-3P2, endometrial thickness of 4.2 mm. When i started treatment with Gnrha ( Leuprolide 11.2 mg depot - planned to be given once every 12 weeks). She received first injection 6 weeks ago. Child is fine for 4 weeks. In the last 2 weeks mother noticed increase in breast size, and since yesterday child is having menstrual bleeding.
A)My query is that "is this due to 1). Insufficient dose/frequency of Gnrha?  Or  2. The hormonal surge  that happens after first injection of Gnrha?

The point against second option is that child is fine for 4 weeks and then developed symptoms of excess ovarian hormone production.
B)Should i change the dose ( increase dose or decrease interval between doses), or just wait and continue with 3 monthly 11.25mg?
C) Is Mepirate warranted at this point of time, given parental anxiety. If used, what is the best dose and duration?
Many thanks for your inputs,  Dr Sirisha Kusuma, Rainbow Children's Hospital, Hyderabad

RESPONSE-Dear Sirisha, This is a very unusual behavior that I never came across treating precocious puberty patients with the GnRHa given every 3 months, though I do not usually use leuprolide. I believe that what happened to this girl is due to the hormonal surge  that happens after first injection of GnRHa, as you mentioned, in combination with a Leuprolide dose insufficient to suppress the axis. Lee PA et al (JCEM 2014) reported  an adequate suppression of the hypothalamic-pituitary-gonadal axis  in 85.2% of patients treated with 11.25 mg of leuprolide and in 94.7%  of those treated with with 30mg. Similar results were reported by Fuld K et al (J Ped 2011) with 66% of patients showing an adequate suppression of the axis with 11.25 mg of leuprolide and 92% of those treated with 22.5 mg. I suggest to increase the Leuprolide dose, depending on the maximal dose available in your country (30 0r 22.5 mg?) starting immediately, without giving a progestin. I’ll be glad to answer any other question you might have. Please keep me updated on the follow-up of this interesting case. Best wishes, Lucia   Ghizzoni, MD

Addendum--Thank you very much for the valuable suggestions. I ended up giving 11.25 immediately. I performed a serum LH level 2 hours after the shot and it was 7.2 ( <6 is taken as suppressed). So it is likely that the dose was not adequate. I am planning to procure 22.5 mg and try it once every 12 weeks.Will update you on the follow up. Sirisha.