Therapeutic potential of human chorionic gonadotropin against overactive bladder - Beyond the Abstract

There are an array of currently therapies for OAB treatment. The main concerns with all of them are the troublesome side effects and contraindications. The side effects primarily come from the non-specific inhibition of muscle contractions in the other organs systems. 

The only U.S. Food and Drug Administration approved (January 2013) therapy for OAB is Botox. Two double blind randomized multi-center placebo controlled clinical trials have shown that Botox treatment improved urgency, incontinence and frequency. But Botox can have serious side effects, including life threatening situations.

hCG, in comparison with the currently available drugs, is a physiological continence hormone. Besides detrusor muscle, hCG can inhibit the contractions of myometrial smooth muscle and vascular smooth muscle in reproductive organs, which explains the minimal side effects.  There are still many unanswered scientific questions with regard to hCG in OAB. Some of the answers come from clinical trials and others from continued hCG research on bladder. In the meantime, the planning of clinical trials, just as those done for Botox, could continue. The trials can also compare single versus combination therapies with Botox and anticholinergics. The combination therapies take advantage of the best features of different drugs, acting by some common and others by different mechanisms. This could make combination therapies more effective than single therapies. Moreover, they can also reduce the doses, toxicities and costs of single therapies with Botox and anticholinergics. 

The optimal dose, route and frequency of hCG administration can be worked out from the experience of using hCG for reproductive medicine indications. However, several iterations in a trial setting are probably required to optimize the treatment conditions. Should hCG be proven effective, there are  numerous possibilities for further improvement on the way hCG is administered. These include, long acting analogs, synthetic mimetics, lozenges that some weight loss clinics use, nanoparticle delivery, etc. 

The proposed clinical trials will be expensive and time consuming. But the potential benefits could be enormous. As any other treatment, hCG may fail in some patients. Thus, the hCG therapy will not be a panacea, but it is likely to become an important part of an Urogynecologists and Urologists tool box. 

hCG therapy is unlikely to work for stress urinary incontinence, for which there are no FDA approved therapies  and overflow incontinence, which comes from kidney producing more urine than the bladder can hold and empty. It is a possible, however, that the hCG therapy may work against painful bladder syndrome/interstitial cystitis, which can ameliorate during pregnancy, ostensibly because of elevated hCG levels. 

Following are additional factors that weigh in favor of the hCG therapy.

a. The minor side effects that are commonly associated with intramuscular injections of hCG do not require medical attention. Even these minor side effects can be side stepped by the bladder wall injections of hCG.  In such cases, half-life considerations of parenteral hCG administration will not be relevant. 

b. hCG is already cheap and can be made even more cost-effective by an increased the production of recombinant hormone

c. The only potential contraindications of using hCG are, women with endometrial and ovarian cancers and Alzheimer’s disease or in those with a strong family history. This contraindications are based on the findings that hCG/LH may promote these diseases . Therefore, it is prudent to withhold the hCG treatment until further data becomes available. 

d. It is unknown whether men’s bladder contains hCG/LH receptors and hCG can inhibit cholinergic stimulation. Yet it is also worth considering the hCG therapy for men. 

e. The possible consequences of chronic hCG administration such as, interruption of cycles, abnormal uterine bleeding, short term infertility and alterations in Leydig cell functions, are a small price to pay in exchange for the potential gain of treatment benefits against this dreadful condition.

Written By:

CV Rao, PhD. 

Professor of Cellular Biology and Pharmacology, Molecular and Human Genetics, and Obstetrics and Gynecology, Director of Reproduction and Development Program, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.

 Read the Abstract

Pelvic Health Weekly Newsletter