Friday, March 26, 2010

Overactive Bladder? Smear the Cream!

There are a variety of proven and efficacious medications available on the market that are approved for Overactive Bladder symptoms of urgency, frequency and urge incontinence. Most of the medications are well tolerated with typical side effects of dry mouth (approximately 25%) and constipation (approximately 10%), which are short-lived (last for a few weeks). Most are once-a-day pills.

Recently released is a gel that can simply be rubbed onto the skin (upper arm usually), once a day, to achieve to same desired results. It is oxybutynin in gel form. It is the “original” overactive bladde drug that comes now in oral generic form, but as a pill it lead to high side effect issues, not only dry mouth and constipation, but sleepiness, concentration issues or short term memory issues, especially in the elderly.

The gel is absorbed through the skin thereby bypassing the liver and therefore minimizes side effects. The study included 352 women. A recent phase III trial reported dry mouth rates of 7.4% and constipation rates of approximately 3%. Application site reaction (rash) was about 2%.

Thursday, March 11, 2010

Flibanserin: A Sex Pill for Woman?

Medications like Viagra, Levitra, and Cialis have revolutionized the male sexual health world, and brought the subject of sex “out of the closet”, for open discussion in the doctor’s office, but also in the media. Commercials for erections are everywhere. The “male pill” has certainly enabled many older men, or men with vascular conditions or injury to regain some sexual potency. Once it debuted in 1998, sex researchers were busily trying to adapt Viagra to women to see if it would help similarly. It does not. It can lead to engorgement of the clitoris, perhaps helping arousal, but it does not help achieve orgasm, increase desire, or decrease sexual pain.

In women, more often than not, desire must precede arousal (though the reverse is true), in order to become romantic. Many things can kill sexual desire: stress, fatigue, bad relationships, menopause, surgery, and many health conditions and the medications taken to treat them, whether physical or psychological. No less important, the loss of sexual desire must be bothersome. For example, if a woman has no sexual desire AND does want to have sex, then her low desire is NOT a problem. It must lead to distress in order to merit treatment of course. So is there help for improving women’s desire on the horizon? Is there a magic pill for women?

Actually, there are medications already on the market that improve sexual desire in women already. I will address testosterone supplementation, which is widely used to restore female libido, in a future post. It is effective and usually given in post-menopausal women, but must be monitored closely with blood tests, and there are risks with hormone replacement, and of course its use is still off-label in the US. Therefore, is there something coming down the pike to help low sexual desire in women?

This past November 2009 a huge pooled phase III study was presented at a sexual conference in Europe. Flibanserin, is still investigational, but may be approved by the FDA within a year or two. In multiple large studies conducted throughout the US and Europe, Flibanserin was shown, if taken once a bedtime, to significantly increased the number of satisfying sexual events and sexual desire, while significantly decreasing distress associated with Hypoactive Sexual Desire in pre-menopausal women. This is incredibly promising and has sex researchers very “excited” about it. It is a novel compound, unlike any other med out there and it is not a hormone.

Is it safe? Most adverse reactions to Flibanserin were mild to moderate. The dose that worked the best with tolerable side effects was 100 mg prior to bedtime. Most side effects were seen within the first 14 days. The pill therefore must be taken daily, as it was studied, in order to achieve its “desired” result of increased sexual desire. We do not know if it can be taken on an as needed basis, like Viagra. The most common side effects included: dizziness, nausea, fatigue, sleepiness and insomnia. They occurred in approximately 15% across all studies, and lead to discontinuation of treatment in those women.

So, how does it work? Flibanserin acts as an agonist and binds to the serotonin 5-HT1A receptor, and an antagonist at the 5 HT2A receptor, in certain brain regions. It acts as a neurotransmitter in the sexual response cycle, and is believed to restore the balance between inhibitory and excitatory factors leading to a better sexual response.

Monday, March 1, 2010

Stress Urinary Incontinence 1 year after Childbirth: Can anything predict it?

It is well known that just being pregnant, is an established risk factor for stress incontinence in women, whether young or middle-aged. Common theories include pelvic floor damage during pregnancy, labor and delivery, as well as chronic stress conditions like coughing, straining, hysterectomy, and genetic linkage.

An interesting question is whether urinary incontinence itself during pregnancy is a risk factor for urinary incontinence after pregnancy, whether immediate or long term. Persistence of urinary incontinence after pregnancy is linked to higher maternal BMI, and those who delivered heavier babies. Most of the studies that look at these risks include women with multiple births, and concluded, rightly, that these variables are causal in the development of urinary incontinence after birth. But what about new-onset stress incontinence during pregnancy- is this linked to higher rates of it after a woman’s first birth?

A study from Spain observed woman during and after their first birth. Questionnaires and exams were performed. Pelvic floor strength was also measured at 6 months post partum. Nearly 400 women were seen in follow up after one year and assessed. The average age of the women was 31 years. Stress incontinence affected 40 (11.4%) of women 1 year after their first delivery. That is a huge number. Out of the total number of women, 4.3% had new onset stress incontinence, while 7.1% reported stress incontinence during pregnancy. When asked to break it down according to severity, 62.5% had “slight”, 32.5% had “moderate”, and 2.5% had severe.
Analysis revealed that women who had stress incontinence during pregnancy and who had vaginal delivery were more at risk for developing stress incontinence 1 year after first childbirth. This factor increased the risk more than 5 times. In addition, the strength of their pelvic floor was also lower on average at 6 months after delivery.

Taken altogether, this is just one more piece of evidence that suggests that women may want to adopt preventative strategies to lessen the risk of stress incontinence, or other consequences of pelvic floor damage by performing pelvic floor muscle training during pregnancy, before pregnancy, as well as perineal massage towards the end of term to prevent tearing during delivery. C-section after obstructed labor is not considered protective against urinary incontinence at 1 year post partum in other studies, and so the data suggest that merely being pregnant can be contributory to development of incontinence, not necessarily mode of delivery.