Dr. Ron’s Research Review – May 19, 2010

 

This week’s research review begins with the recent JAMA article.

Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence. (Shu, Zheng et al. 2009)

 

The next article brings up hair loss (androgenic alopecia) and aromatase.

Both young women and young men with androgenetic alopecia have higher levels of 5alpha reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. (Price 2003)

 

A comprehensive review of estrogens and hair growth was published in Endocrine Reviews. (Ohnemus, Uenalan et al. 2006)

The hair follicle is the only organ that undergoes a lifelong cyclic transformation, characterized by three distinct stages: growth (anagen), regression (catagen), and resting (telogen).

Estrogens have been used for topical treatment of hair diseases for more than half a century and constitute a firm staple of management strategies for female pattern androgenetic alopecia in central Europe.

Topical formulations containing either 17beta- or 17alpha-estradiol have long been successfully employed for the treatment of androgenetic alopecia, where they appear to improve the telogen/anagen ratio of scalp hair follicles. (17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol).

E2 has long been recognized to profoundly modulate hair growth, acting primarily as a hair growth inhibitor. This hair growth-inhibitory activity reported in mice strikingly contrasted with the supposedly hair growth-stimulatory topical E2 therapy long practiced in many countries for the treatment of female pattern androgenetic alopecia and the hair loss induced by therapy with aromatase inhibitors, which lower serum and tissue E2 levels

 

 

Dr. Ron

 

 


Abstracts

Soy food intake and breast cancer survival

            (Shu, Zheng et al. 2009) Download

CONTEXT: Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients. OBJECTIVE: To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence. DESIGN, SETTING, AND PARTICIPANTS: The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information. MAIN OUTCOME MEASURES: Total mortality and breast cancer recurrence or breast cancer-related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable. RESULTS: During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. CONCLUSION: Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

 

The hair follicle as an estrogen target and source

            (Ohnemus, Uenalan et al. 2006) Download

For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17beta-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.

 

Androgenetic alopecia in women

(Price 2003) Download

Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5alpha reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.


References

Ohnemus, U., M. Uenalan, et al. (2006). "The hair follicle as an estrogen target and source." Endocr Rev 27(6): 677-706.

Price, V. H. (2003). "Androgenetic alopecia in women." J Investig Dermatol Symp Proc 8(1): 24-7.

Shu, X. O., Y. Zheng, et al. (2009). "Soy food intake and breast cancer survival." JAMA 302(22): 2437-43.