Less Carcinogenic Chlorinated Estrogens Applicable to Hormone Replacement Therapy

Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE2) or 4-chloro-17β-estradiol (4-ClE2) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer. 17β-Estradiol (E2) frequently induced mammary tumors while both 2-ClE2 and 4-ClE2 did not. Their 17α-ethinyl forms, thought to be orally active estrogens, were also synthesized. Neither 2-chloro-17α-ethinylestradiol (2-ClEE2) nor 4-chloro-17α-ethinylestradiol (4-ClEE2) induced tumors. The less carcinogenic effects were supported by histological examination of mammary glands of ACI rats treated with the chlorinated estrogens. A chlorine atom positioned at the 2- or 4-position of E2 may prevent the metabolic activation, resulting in reducing the carcinogenicity. 2-ClE2 and 4-ClE2 administered subcutaneously and 2-ClEE2 and 4-ClEE2 given orally to ovariectomized rats all showed uterotrophic potency, albeit slightly weaker than that of E2. Our results indicate that less carcinogenic chlorinated estrogens retaining estrogenic potential could be safer alternatives to the carcinogenic estrogens now in use for HRT.

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Beneficial Role of Hydro-alcoholic Seed Extract of Trigonella foenum graecum on Bone Structure and Strength in Menopause Induced Osteopenia

Ethiopian Journal of Health Sciences ◽

10.4314/ejhs.v28i6.14 ◽

1970 ◽

Vol 28 (6) ◽

Author(s):

Anjaneyulu K ◽

Kumar MR Bhat ◽

Srinivasa SR ◽

Devkar RA ◽

Henry T

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Bone Structure ◽

Hormone Replacement ◽

Biomechanical Properties ◽

Seed Extract ◽

Ovariectomized Rats ◽

Trigonella Foenum Graecum ◽

17Β Estradiol

BACKGROUND: The current strategies to prevent and treat menopausal osteoporosis are hormone replacement therapy (HRT). However, the long-term use of hormone replacement therapy is limited due to its side-effects. Alternately, use of phytoestrogens has been implicated. Trigonella foenum graecum (TFG) seeds are rich in phytoestrogen and known traditional medicine to treat menopause induced hyperlipidemia. Therefore, in this study, we evaluated the role of dietary TFG seed extract on bone structure and mechanical properties in ovariectomized rats.METHODS: Twenty four female Wistar rats were randomly allocated into four groups; 1) control, 2) ovariectomized, 3) ovariectomized + TFG seed extract and 4) ovariectomized + 17β-estradiol. TFG seed extract/17β-estradiol was administered for 30 days, 14 days after ovariectomy. After the treatment, right femora were collected to measure the length and biomechanical properties, and left femora were gathered to study the micro architectural changes while tibia were collected to measure the dry weight.RESULTS: Maximum flexor load to break femur bone was significantly low in ovariectomized rats in comparison with control rats (P<0.05). Supplementation with TFG significantly improved the maximum flexor load (P<0.05) and tibia dry weight (P<0.01) compared to ovariectomized untreated rats. TFG administration also significantly preserved the trabecular (P<0.01) and cortical bone (P<0.05) thickness compared to ovariectomized rats.CONCLUSION: This study found that dietary intake of TFG seeds can improve the bone structure and biomechanical properties in ovariectomized rats indicating that TFG may be an alternative treatment strategy to prevent the menopause induced osteopenia.

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Effects of Hormone Replacement Therapy on Plasma and Tissue Fibrinolytic Activity in a Rat Model of Surgically Induced Menopause

Clinical & Investigative Medicine ◽

10.25011/cim.v37i2.21090 ◽

2014 ◽

Vol 37 (2) ◽

pp. 85 ◽

Cited By ~ 1

Author(s):

Ata Topcuoglu ◽

Mustafa Albayrak ◽

Hayriye Erman ◽

Huriye Balci ◽

Mesut Karakus ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Oral Administration ◽

Replacement Therapy ◽

Plasminogen Activator ◽

Brain Tissue ◽

Fibrinolytic Activity ◽

Hormone Replacement ◽

17Β Estradiol ◽

Surgically Induced ◽

Pai 1

Purpose: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. Methods: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200–250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. Conclusions: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.

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