Estrogen-Depleted Geese, Meet Androgen-Compromised Ganders

Speaking, or rather screeching, as a menopausally-crazed, cognitively-impaired winged harpy, I feel it is my duty to swoop in and squawk about the recent hormone replacement therapy free-for-all that's goin' down at Science Blogs.

Links are hardly necessary given that this is front page news but those of you who have wandered into this mess of bonobo scat and banana peels called the Chimp Refuge can scurry off to Neurotopia v.2 where another insidious primate provides extensive and authoritative reviews in three parts. I'd just like to point out a couple of things. I may have missed these since I am a doddering old broad, but hey, old people repeat themselves all the time. Get used to it. It will happen to you. Oh, and we ramble on and on, too. Anyway, where was I? Where am I? Oh, yeah...

1. Cognitive decline also occurs in aging men.

2. Increased rates of Alzheimer's Disease (AD) in women may be due to the fact the women live longer; more importantly, it is not altogether clear that the decline of sex hormones influences the development of AD (see below).

Although men do not go through a clear cut shut-down of testosterone and related steroids, there is such as beast as "andropause" as the levels of testosterone and his steroidal brethren decline with age. Let's take a look at what happens as androgens decline in men:

From Science Daily: Testosterone Therapy May Help Elderly Men With Mild Alzheimer's Disease

"There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD)," the authors provide as background information in the article. They note that hormonal therapies have been the focus of research attention in recent years since male aging is associated with a gradual progressive decline in testosterone levels. "The gradual decline in testosterone level is associated with decreased muscle mass and strength, osteoporosis, decreased libido, mood alterations, and changes in cognition, conditions that may be reversed with testosterone replacement." Bolded text - Doc Bushwell. The authors add that the age-related decline in testosterone is potentially relevant to AD as previous studies have found significantly lower concentrations of the hormone in middle-aged and elderly men who developed AD.

Wow! Decreased muscle mass, decreased libido, mood alterations and what's that you say, sonny...changes in cognition? Well, damn, you ol' boys better slap on a testosterone patch or swallow that Big T-pill! What? You're concerned about triggering hormone-dependent prostate cancer? Hmmm. Let's see, a lot of men in the USA, i.e, those with a Western based high fat diet since youth, have precancerous lesions in their prostate glands even in their twenties, and as men age, those lesions increase and transform. So, yeah, that testosterone patch you slap on your arm or the pill you swallow might just nudge things along. But think...think! It's your cognition we're talking about! Goodness knows that one can't be allowed to be a little foggy past age 55. And forget the fact that physical and mental exercise contribute significantly to quality of life for the geriatric individual. Let's keep those nuclear hormone receptors jazzed up!

Analogously, you might see why a menopausal woman with intact ovaries and one with an icky familial cardiovascular history might be circumspect about the glories of estrogen replacement. My hat's off to young Jake at Pure Pedantry for noting right up front that estrogen replacement is recommended for acute treatment only.

As much as I love better living through chemistry, and as much as I want you all to squander money on Rx drugs so that I might wrap myself in a dowager's chinchilla coat, consider this rant to be a warning to be very, very careful out there with regard to estrogen- or androgen-replacement therapies. I'm speaking not only as a menopausal madwoman, but also as the former head of a prostate cancer program and as a current herder of cats who oversees projects with potential off target effects on neurosteroid metabolizing enzymes. The various animal studies are interesting, to be sure, but warrant careful scrutiny. So if it's good for the goose, it's good for the gander, right? Or maybe not.

Actually, the role of estrogen in the pathology of Alzheimer disease has been questioned. Luteinizing hormone may be a more significant factor. Check out the following abstract. Also, inflammation plays a major role in AD, and that has a pretty complex etiology.

Mol Cell Endocrinol. 2007 Jan 2;260-262:271-5. Epub 2006 Oct 18. Links
Gonadotropins: a cohesive gender-based etiology of Alzheimer disease.

Webber KM, Casadesus G, Atwood CS, Bowen RL, Perry G, Smith MA.
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

While there is ample experimental evidence supporting the role of estrogen in the pathogenesis of Alzheimer disease, recent inconclusive data regarding hormone replacement therapy (HRT), specifically, the unexpected results of the Women's Health Initiative (WHI) Memory Study has raised serious questions regarding the protective effects of estrogen. Because of this and other inconsistencies in the estrogen hypothesis, we propose that another hormone of the hypothalamic-pituitary-gonadal axis, luteinizing hormone, is a major factor in the pathogenesis of Alzheimer disease. Specifically, we suspect that the increase in gonadotropin concentrations, and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause, is a primary causative factor for the development of Alzheimer disease. In this review, we examine how the gonadotropins may play a central and determining role in modulating the susceptibility to, and progression of, Alzheimer disease.