LICHEN SCLEROSIS, ANDROGENS, ADRENALS AND THE NARROW, GILDED PASSAGEWAY TO HEALTHY CRONEHOOD

(OR HOW THE MEDICAL SYSTEM FAILS WOMEN)

Part 1. Hysterectomy and the long-term health of women.

As research subjects go, women are not very popular with medical science. Surely we are worthy, but the gigantic medical-pharmaceutical machine that is now our health care system seems to place more value on marketing our diseases than restoring us to health. There is no other way to interpret such profound abandonment. Far more dangerous than neglect are the ways in which medical science adapts the truth to fit its own needs, even at the expense of healthy women.

Fortunately, unbiased and insightful researchers employing good science continue to correct old and entrenched untruths within the gynecologic literature. It is imperative that their work be popularized.

Every year in the United States 600,000 women lose their uterus to hysterectomy. Half of these women also forfeit their ovaries in the same procedure, almost all for benign disease. Yet, a paucity of data exists showing how these operations influence endocrine function. Fewer reports can be found on the natural workings of the healthy, post-menopausal ovary.

More exasperating than the dearth of studies is the tremendous contradiction of results that goes on from year to year. At what point can we decide that yes, removing the uterus causes severe and irreversible damage to ovarian function without yet another group of researchers refuting the truth? Recent contributions to the medical literature may put to rest any question that the uterus and ovaries are organs vital to the health and well-being of women of all ages.

Rarely in modern times has it been contested that removing both ovaries causes sudden and severe “surgical menopause.” Yet, routine prophylactic bilateral oophorectomy is often performed in women over 40 years of age. Prevention of ovarian cancer is the most common rationale given for the procedure even though it is known that for every 1000 cases of cancer prevented, 300,000 oophorectomies are performed.¹ A far more plausible reason is that non-malignant pathology in retained ovaries forces a reoperation rate of 5% to 8% in women who have had a previous hysterectomy.²

The effects of hysterectomy on retained ovaries remains controversial. Past studies indicate that ovarian function is affected after hysterectomy while other reports suggest no decrease in ovarian reserve. The controversy seems to be resolving, however, as several independent, inter-disciplinary teams from around the world using state of the art technologies contribute to the medical literature.

Gynecologists from China using both serum hormone analysis and Doppler ultrasonography studied the relationship between ovarian blood supply and ovarian function.³ While it had been previously observed that blood flow to the ovaries initially increases after hysterectomy⁴ it was not understood why. These researchers concluded that the increase of velocity of blood flow is actually a compensatory response of the ovarian arteries: “The total blood supply to the ovary was reduced due to the lack of blood coming from the uterine arteries after hysterectomy, and therefore, the ovarian arteries increase their flow speed in order to receive enough blood supply.” However, the total blood supply to the ovary is decreased, which causes reduced secretion of endocrine hormones. This reduced secretion of hormones further reduces blood flow in the ovarian artery. “Both factors promoted each other, enhanced the reduction of ovarian function and endocrine function.”

A research group from India has recently measured oxidative stress of hysterectomy and hysterectomy with bilateral oophorectomy.⁵ Serum levels of antioxidants were lower and free radicals higher in both groups.

A stunning illustration of the damage sustained by hysterectomy comes from the Netherlands where a group of researchers compared loss of ovarian function in both uterine artery embolizaton (UAE) and hysterectomy.⁶ In this study very few differences in effect on ovarian function were found between UAE and hysterectomy. Both procedures caused damage to the ovaries, as substantiated by significant increases in serum follicle stimulating hormone (FSH) and luteinizing hormone (LH). Blood levels of anti-Mullerian hormone (AMH) were also measured as an even more accurate indicator of ovarian function. “The decrease in AMH in the first 24 months, which was not correlated with age, indicates that every woman experiences loss of ovarian reserve.”

The importance of ovarian function in postmenopausal women was recently highlighted by researchers at the University of Southern California.⁷ This team concluded that the postmenopausal ovary is hormonally active, contributing significantly to the circulating pool of endogenous androgen. Androgens are not just male hormones, but necessary for the health of genital, brain, bone, breast, skin, skeletal muscle, and fat tissue in women. They are also the major precursors for estrogen production. This study corroborates an earlier one⁸ that demonstrated the postmenopausal ovary is a critical source of androgen throughout the lifespan of older women.

To summarize:

• The ovaries are the major source of androgens in the postmenopausal woman.
• Androgens are vital for female health.
• Hysterectomy diminishes and often destroys ovarian function.
• Other common procedures such as UAE also damage ovaries.

Part 2. CASE STUDY: Lichen Sclerosis and a failed system of medicine.

Lichen sclerosis (LS), a skin disease affecting primarily the genitals, was first described in 1875. Although extremely rare in children and men, LS occurs frequently in perimenopausal and menopausal women. It is a disease of the skin of the clitoris, vulva, and anus that in the early stages mimics thrush yet often progresses to serious and debilitating symptoms. The skin becomes thin and papery and can easily tear, split, fissure and bruise. Small papules are sometimes present extending into the hair follicles in the crease of the upper thigh and perineum. Incapacitating itching that is worse at night are classic signs of LS. Forced celibacy is often the rule and in extreme cases the clitoris and vaginal opening become covered over with tightened, sclerosed tissue.

Although frequently associated with an increased incidence of squamous cell carcinoma of the vulva, no significant correlation between LS and cancer has ever been found.⁹

How commonly LS occurs is not known, as there are no statistics about the disease. However, it is prevalent enough to be highlighted on every women’s health network on the Internet. Dr. Judith Reichman, reporting on lichen sclerosis at MSNBC.com, provided a glaring example of the illogical medical approach to the disease: “We don't know why this disorder occurs, but we do know how to treat it.”

Quite the contrary, researchers have long suspected why LS occurs,^10,11 yet the medical system only treats its symptoms while the underlying disease often progresses unabated.

It has long been established that women with LS have low levels of circulating androgens and that androgen-sensitive cells in genital skin facilitate the collagen production that supports its basic structure. Studies have also looked into autoimmune processes and infectious agents as causes of LS, but these have yielded no conclusive results.

A cursory look at the physiology of female androgen production will help us understand the relationship between androgen levels and vulvar lichen sclerosis.

As previously stated, testosterone is a biologically active androgen in both males and females. Healthy premenopausal women produce approximately 5% of the daily production of testosterone in males. Androgens in women either derive from direct ovarian production or from peripheral conversion in fat tissue of the adrenal sex steroid precursor, dehydroepiandrosterone (DHEA). Stimulation for androgen production is regulated by the pituitary gland. Female androgen production therefore requires coordination of the ovaries, the adrenals, and the pituitary and adequate production depends upon this intact hormonal axis.¹²

It has been shown that a rather abrupt decline in ovarian production of testosterone occurs around the time of menopause in healthy, intact women.^13,14,15 However, year by year ovarian production increases until it once again reaches premenopausal levels with stable levels thereafter.¹⁶

However, the opposite can be said of adrenal androgen production. As women age, the area of the adrenal gland that secretes androgens thins, atrophies, and eventually disappears in aging women. Therefore, adrenal androgen production in post-menopausal women is a small fraction of that in pre-menopausal women.¹⁷

Androgens released into the blood stream bind to a protein called sex steroid binding globulin (SHBG). The levels of free, or bioavailable, androgens are the unbound circulating androgens that can bind to androgen receptors. In the unbound state, androgens act on genital structures and many other sites including brain, bone, breast, skin hair follicles, skeletal muscle, and fat tissue.

Levels of SHBG directly affect concentrations of free androgens, especially testosterone, which has the highest affinity for SHBG. Exogenous estrogens increase the levels of SHBG and consequently decrease levels of bioavailable androgens, which can lead to androgen deficiency.

To summarize:

• LS is primarily a disease of perimenopausal and early menopausal women
• LS is not a precancerous condition
• There is little data to support primary autoimmune or infectious processes in LS
• LS is correlated with androgen deficiency
• There is a gap at the onset of menopause when ovarian androgen production sharply declines as adrenal androgen production is slowly declining.
• Ovarian production of testosterone picks up after menopause until once again reaching premenopausal levels and stabilizing into old age.
• Adrenal stress and exogenous estrogens cause available testosterone to bind to increased concentrations of SHBG.

Once this sequelae was understood, doctors began treating LS with topical testosterone. However, masculinizing effects occur with even small doses making it unacceptable for women.

Current treatment focuses on the use of superpotent topical corticosteroids (Clobetasol or Temovate), thought to decrease inflammation and itching by inducing specialized proteins that control synthesis of the mediators of inflammation. Physician warnings about Clobetasol include the following:

“May suppress adrenal function in prolonged therapy; observe for evidence of steroid atrophy; consider biopsy to exclude malignancy in patients with genital LS who have good response yet have a single persistent lesion involved or ulcerated area.”

The latest medicine offered to women with LS is the organ transplant drug Tacrolimus (Protopic), which suppresses the body’s immune system. Patient information on Tacrolimus includes the following:

“The immune system helps your body fight infections. The immune system can also fight or ‘reject’ a transplanted organ such as a liver or kidney. This is because the immune system treats the new organ as an invader.”

To summarize:

• Although mid-life vulvar LS is largely a disease of androgen deficiency, it cannot be treated with topical testosterone.
• Instead, standard treatments attempt to control the symptoms of LS with highly potent corticosteroids and immunosuppressants.
• The superpotent corticosteriods suppress function of the adrenals, the major source of androgens in the perimenopausal woman.
• The immunosuppressants inhibit the genetic transcriptions involved in T-cell activation, making vulvar tissue more susceptible to malignant changes.
• LS is now considered an autoimmune and precancerous condition.

COMMENTARY

It seems clear that mid-life vulvar LS is a common metabolic disorder being treated with super potent medications that can only cause further endocrine disruption and worsening of the disease.

DHEA, as well as its sulfate ester (DHEAS) and androstenedione, are the corticosteroid “androgens” secreted by the adrenal cortex. It has long been observed that patients on corticosteroid therapy have low DHEA levels because hormonal feedback loops signal the adrenals to suppress production. Therefore, placing women with LS on superpotent topical corticosteroids can only shut down secretion of DHEA in a system already deficient of circulating androgens. Is it any wonder that many of these women suffer with LS for decades and go on to develop additional “autoimmune” disorders?

If the above thesis is correct, restoring healthy adrenal function is the primary treatment for LS. If a woman has lost ovarian function through hysterectomy and oophorectomy, androgen metabolite therapy may be appropriate. DHEA is classified as a food supplement in the United States and sold over the counter. Ironically, DHEA is considered a wonder drug by many health advocates while being virtually ignored by the medical profession. Exogenous DHEA is not without risks, however, and should only be taken under the guidance of a health professional.

The same gland that secretes the androgens necessary for vulva health also produces our stress hormones. Chronic stress exhausts the adrenals and may cause an accelerated decline in the production and secretion of DHEA. In early menopausal women with depressed ovarian testosterone production, restricted adrenal output may lead to systemic androgen deficiency and LS.

Lowering stress and boosting the health of the adrenal glands might be all that is needed to resolve most cases of vulvar LS.
The following are just a few ways to begin to support adrenal health.

1. Reduce personal and job stress
2. Improve relationships
3. Keep regular hours
4. Do not overwork
5. Exercise
6. Eat a healthy diet
7. Limit alcohol, sugar, and refined foods
8. Do not take stimulants
9. Do not watch violent TV or movies

Lichen sclerosis is just one example of a debilitating disease that may be preventable by cultivating a strong endocrine system. There are many other such diseases involving thyroid, heart, brain, blood, and bones. Healthy, intact women can look forward to life-long ovarian production even as adrenal function naturally wanes. Consequently, any medical or surgical procedure that places the uterus or ovaries at risk should be considered in view of metabolic health across the female lifespan.
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1. Hendrix S Bilateral oophorectomy and premature menopause. The American Journal of Medicine. 118(12B); 131S-135S
2. Nahas P et al Effect of total abdominal hysterectomy on ovarian blood supply in women of reproductive age. Journal of Ultrasound Medicine 24:169-174 2005
3. Xiangying H Lili H Yifu S The effect of hysterectomy on ovarian blood supply and endocrine function. Climacteric 9:283-289 2006
4. Nahas ibid
5. Kaur et al Retention of ovaries and oxidative stress of surgery International Journal of Gynecology and Obstetrics 97:40-43 2007
6. Wouter et al Loss of ovarian reserve after uterine artery embolization:a randomized comparison with hysterectomy. Human Reproduction 22(7):1996-2005 2007
7. Fogle et al Ovarian androgen production in postmenopausal women. The Journal of Clinical Endrocrinology and Metabolism 92(8): 3040-3043 2007
8. Laughlin et al Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Ranch Bernardo study Journal of Clinical Endocrinology and Metabolism 85(2): 645-655 2000
9. Meffert J, Davis B, Grimwood R Lichen sclerosis The American Journal of Dermatology 32(3): 393-416 1995
10. Joura E et al Short-term effects of topical testosterone in vulvar lichen sclerosis. Obstetrics & Gynecology 89: 297-299 1997
11. Friedrich E Kalra P Serum levels of sex hormones in vulvar lichen sclerosis and the effects of topical testosterone The New England Journal of Medicine 310: 488-491 1988
12. Bachmann G Oza D Female androgen insufficiency Obstetrics and Gynecology Clinics 33(4) 2006
13. Rannevik G et al A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary horones, SHBG and bone mineral density. Maturitas 21: 102-113 1995
14. Overlie I et al The endocrine transition around menopause: a five years prospective study with profiles of gonadotropins, estrogens, androgens and SHBG among healthy women. Acta Obstetrica Gynecologica Scandanavia 78: 642-647 1999
15. Jiroutek M Changes in reproductive hormones and sex hormone-binding globulin in a group of posmenopausal women measured over 10 years. Menopause 5:90-94 1998
16. Laughlin 2000 ibid.
17. Buster J et al Treatment of the Postmenopausal Woman:basic and Clinical Aspects 2nd ed. Lippincott, Williams& Wilkins 1999 p.142