Parenteral Estrogens for Prostate Cancer: Can a New Route of Administration Overcome Old Toxicities?

Lycette, Jennifer; Bland, Lisa B.; Garzotto, Mark; Beer, Tomasz M.

doi:10.3816/cgc.2006.n.037

Cited by 6 publications

(4 citation statements)

References 67 publications

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“…There is indeed a difference between metabolic effects of oral and parenteral estrogens; although oral estrogen therapy is known to be associated with thromboembolic complications, studies of parenteral estrogen in men with prostate cancer suggest that the use of parenteral estrogen achieves target androgen suppression, does not adversely affect prothrombotic protein levels, and is not associated with adverse metabolic, skeletal, and body compositional changes when compared with conventional ADT (35).…”

Section: Effects Of Cross-sex Hormone Treatment On Cardiovascular Heamentioning

confidence: 99%

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

Gooren

Wierckx

Giltay

2014

European Journal of Endocrinology

113

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Objective: The incidence of heart disease increases with age, but is lower in women than in men up to 75 years. A protective effect of female sex hormones or, alternatively, acceleration in male heart disease by testosterone at younger ages, could explain this sex difference. In contrast with the above, male-to-female transsexual subjects (MtoF) treated with estrogens (Canti-androgens) show more cardiovascular pathology than female-to-male transsexual subjects (FtoM) receiving testosterone. Why MtoF suffer more frequently from cardiovascular disease than females is as yet unclear. The mode of cross-sex hormone treatment may be a factor, and, if so, it may need adaptations. Subjects and methods: Studies in transsexual people on the effects of cross-sex hormone treatment on surrogate cardiovascular risks and on clinical endpoints were reviewed. With regard to MtoF, a parallel was sought with men with prostate cancer, undergoing androgen deprivation and estrogen administration. Results: Exposure of FtoM to testosterone was not associated with a strong increase in cardiovascular events. Aging and pre-existing cardiovascular pathology contributed to the risk of cardiovascular disease in MtoF. Use of the synthetic biopotent compound ethinyl estradiol in a dose two to four times of oral contraceptives increased cardiovascular risk substantially. The route of administration of estrogens (oral vs transdermal) may have impacted on the risks. Conclusion: MtoF should not be treated with oral ethinyl estradiol. Transdermal estrogens are probably safer than oral estrogens. Pre-existing cardiovascular risks should be taken into consideration when prescribing and choosing the type of estrogens in crosssex hormone administration (oral vs transdermal). In addition, risk factors, as they emerge with aging, should be addressed.

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Section: Effects Of Cross-sex Hormone Treatment On Cardiovascular Heamentioning

confidence: 99%

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

Gooren

Wierckx

Giltay

2014

European Journal of Endocrinology

113

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“…In fact, prior studies have supported that estrogen administrated via intramuscular or a transdermal route, as opposed to orally, is less thrombogenic by avoiding exposure of the liver to high estrogen concentrations from the hepatic circulation, which results in increased synthesis of thrombophilic coagulation factors [22–25]. Specifically, oral estrogen leads to increased factor VIII activity, increased factor VII and increased resistance to activated protein C among other changes [26]. Other toxicities were also uncommon including grade 1 gynecomastia reported in only 9% of patients enrolled on the present trial.…”

Section: Discussionmentioning

confidence: 99%

Transdermal estradiol in castrate and chemotherapy resistant prostate cancer

et al. 2012

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SummaryBackgroundGiven prior studies demonstrating the marked clinical activity of oral estrogens in prostate cancer, more recent data demonstrating the safety of transdermal estradiol, and the renewed interest in targeting testosterone metabolism and androgen receptor pathways, we report the results of a trial of transdermal estradiol in advanced heavily pre-treated castrate and chemotherapy refractory patients.Material/MethodsPatients with prostate cancer progressing after androgen ablation therapy and chemotherapy were treated with transdermal estradiol patches (0.4 mg per 24 hours total) applied weekly and assessed for tolerability and biochemical activity.ResultsTwenty-two patients were treated on study with all patients evaluable for safety and 20 patients evaluable for response. All patients had aggressive and resistant disease, as demonstrated by a median PSA of 170 ng/mL (range 14 to 5030 ng/mL), with more than 60% having been treated with two or more prior chemotherapy regimens, and 20% with visceral disease. Nine patients had a decrease in PSA, of which two patients had a PSA response defined as a decline in PSA by 50%. Therapy was well tolerated and no thrombotic events were observed.ConclusionsIn heavily pre-treated patients with advanced castrate and chemotherapy refractory metastatic prostate cancer, transdermal estradiol was safe and had biochemical activity. These data support further studies to understand if transdermal estradiol can be useful following multiple standard therapies.

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“…Transdermal preparations typically peak within several hours of administration and typically last 7 days and are recommended to be applied once to twice per week depending on the manufacturer [ 16 ]. Patch and gel administration is associated with a high variation in circulating estradiol values—even within the same patient in cisgender women [ 18 ]. Areas of application may affect absorption with significant differences in bioavailability (scrotum, abdomen, buttocks regions have the highest absorptions).…”

Section: Gender-affirming Hormone Therapy Preparationsmentioning

confidence: 99%

An Approach to Nonsuppressed Testosterone in Transgender Women Receiving Gender-Affirming Feminizing Hormonal Therapy

Maheshwari

Nippoldt

Davidge‐Pitts

2021

Journal of the Endocrine Society

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Non-suppressed levels of testosterone are seen in up to a quarter of transgender women on gender affirming feminizing hormonal treatment. Multiple factors contribute to this situation including patient, medication, laboratory, and organ specific concerns. We propose a stepwise approach to determine the etiology of non-suppressed levels of testosterone in transgender women. This may lead to an appropriate feminizing hormonal therapy regimen and diagnosis of manageable medical conditions.

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Parenteral Estrogens for Prostate Cancer: Can a New Route of Administration Overcome Old Toxicities?

Cited by 6 publications

References 67 publications

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

Transdermal estradiol in castrate and chemotherapy resistant prostate cancer

An Approach to Nonsuppressed Testosterone in Transgender Women Receiving Gender-Affirming Feminizing Hormonal Therapy

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