Rationale for low-dose systemic hormone replacement therapy and review of estradiol 0.5 mg/NETA 0.1 mg

Johansen, Odd Erik; Qvigstad, Erik

doi:10.1007/s12325-008-0070-6

Cited by 11 publications

(5 citation statements)

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“…The use of moderate estrogen doses and the means of administration have been described previously. 9,30 The effective doses of 17 -estradiol (E2) and norethisterone acetate we selected were based on the concentration capable of inhibiting oxidative stress. 9,30 The current study shows the extent of OPD in this model of estrogen deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…9,30 The effective doses of 17 -estradiol (E2) and norethisterone acetate we selected were based on the concentration capable of inhibiting oxidative stress. 9,30 The current study shows the extent of OPD in this model of estrogen deficiency. The protective effects of estrogenprogestin combinations against tissue specific OPD suggest that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain.…”

Section: Discussionmentioning

confidence: 99%

“…8 Norethisterone acetate is a 19nortestosterone-derived progestin, with potent effects on minimizing estrogen-induced endometrial stimulation, even at very low doses. 9 Drospirenon is the first synthetic progestin with antimineralocorticoid activity, has a similar effect to progesterone itself and is structurally related to 17 -spirolactone used in contraception and in post-menopausal hormone replacement therapy (HRT). Drospirenon has anti-mineralocorticoid activity in the kidney as reflected by elevated natriuresis.…”

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confidence: 99%

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Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Topçuoğlu¹,

Uzun²,

Balcı³

et al. 2009

CIM

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Purpose: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats Methods: Twelve-week-old, sexually mature female Sprague–Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17?-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH). Results: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05) Conclusions: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Topçuoğlu¹,

Uzun²,

Balcı³

et al. 2009

CIM

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“…Различные комбинации обеспечивают специфические преимущества. Согласно современным рекомендациям, основной целью лечения является достижение контроля симптомов с использованием минимальной эффективной дозы МГТ [8,10]. Низкие дозы эстрогенов требуют сочетания со сравнительно низкими дозами прогестагенов для обеспечения безопасности эндометрия.…”

Section: пре-и постменопаузаunclassified

Menopausal Hormone Therapy With Dydrogesterone: Aspects of Efficacy and Safety of Ultra-Low Doses

Smetnik

2017

Medicinskij sovet

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A number of studies have shown that menopausal hormone therapy (MHT), consisting of 1 mg 17ß-estradiol and 5 mg dydrogesterone, is effective to reduce the severity of menopausal symptoms and increases bone mineral density in postmenopausal women [1] and at the same time has a favorable safety indicators for the endometrium and the pattern of bleeding [2, 3]. Nevertheless, current guidelines recommend the use for the treatment of menopausal symptoms of the lowest effective dose of estrogen [4–6]. In this regard, we developed a new combined mode of MHT with continuous use of ultra-low doses of hormones – 0.5 mg 17ß-estradiol and 2.5 mg of dydrogesterone. The use of ultra-low doses of estrogen protects the endometrium by lower doses of progestogen. Similar combinations of low doses of MHT can reduce the incidence of adverse events, such as the sensitivity of the mammary glands, uterine bleeding, cardiovascular disease, ischemic stroke and venous thromboembolic complications, and at the same time, to maintain effectiveness against menopausal symptoms [7–11]. The appearance of in the arsenal of gynecologists of ultra-low dose MHT is likely to improve the patient’s adherence to this treatment regime. In addition, a low dose of estrogen is particularly useful for older women (>59 years).

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“…Several papers have indicated a dose dependency for HRT [ 14 ]. Therefore, it is logical to evaluate the effectiveness, the tolerability and the adverse effects of low doses of HRT [ 15 ].…”

Section: The Lower Effective Dosementioning

confidence: 99%

Advances in hormone replacement therapy: making the menopause manageable

Palacios

2008

BMC Women's Health

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The importance of the results of some large, randomized controlled trials (RCTs) on Hormone Replacement Therapy (HRT) has modified the risk/benefit perception of HRT. Recent literature review supports a different management.The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch.The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.

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Rationale for low-dose systemic hormone replacement therapy and review of estradiol 0.5 mg/NETA 0.1 mg

Cited by 11 publications

References 142 publications

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Menopausal Hormone Therapy With Dydrogesterone: Aspects of Efficacy and Safety of Ultra-Low Doses

Advances in hormone replacement therapy: making the menopause manageable

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