using HPG-minidosing to maintain the natural timing of puberty

The goal of HPG-minidosing is to slow down the early activation of the gonads (HPG axis), while HPA-minidosing works to counteract any early rise in adrenal androgens (HPA axis).

HPG-minidosing is a weak suppression based on the feedback enhancement of progestational action and needs to start at the earliest clinical signs of gonadal activation if it is to be effective. This is typically about three years before the more obvious cues that most parents would recognize as puberty. If the gonads have recently become activated (testicle length greater than 2cm in boys, or the presence of breast buds in girls), then HPG-minidosing may be be effective.

The child's physician will first exclude all other illnesses which can cause the symptoms of early puberty. If deemed appropriate, HPG-minidosing should be planned and monitored by someone fully familiar with pediatric endocrinology.

In HPG-minidosing, HPA axis symptoms may be treated first with tiny fractions of a dose of antiandrogen to neutralize the adrenal androgens of premature or exaggerated adrenarche. Metformin may help reduce excess androgens in the overweight child. An example of HPG-minidosing: An eight-year-old Canadian boy is referred to the doctor with behavioral problems (his teacher expecting a diagnosis of ADHD). He may have been growing more quickly than his peers, and be closer to the size of a normal ten-year-old. The doctor finds that the boy has begun to sprout pigmented hairs amongst the normal vellus hairs on his pubis, and he has some acne pimples on his nose. These are all signs of excess adrenal androgens, which may be treated with HPA-minidosing. But if the gonads have become activated (testicle length greater than 2cm in boys, or the presence of breast buds in girls), then HPG-minidosing may be necessary.

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In Canada, cyproterone acetate (CPA) may be prescribed as antiandrogen/progestin. A tiny amount, perhaps 5mg or 10mg/day is enough. Small amounts of an aromatase inhibitor such as anastrozole tablets are added to prevent any estrogen induced effects such as gynecomastia and bone growth plate closure. The progestational action of the CPA will help keep the HPG axis dormant until such time as progression into puberty is desired.

In the United States, the HPG-minidosing concept would be the same, but a combination of spironolactone and medroxyprogesterone may be used instead of CPA.

Antiandrogens and progestins are known to be harmful in large doses. In cases which have progressed beyond the control of small-dose treatment strategies, and if the child is still so young that further delay of puberty is appropriate, then it is better to move on to GnRh-analog treatment.