Pharmacokinetics of Fem7&lt;sup&gt;®&lt;/sup&gt;, a Once-Weekly, Transdermal Oestrogen Replacement System in Healthy, Postmenopausal Women

Geyer, Daniel J; Gerrits, Mireille; Renoux, A.; Uhl, Wolfgang

doi:10.1159/000010124

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…This is illustrated in Fig. 1 for two 100 μg/day patches, Fem7 and Estradot (Novartis Pharmaceuticals UK Ltd., Frimley, Surrey, UK), for which published oestradiol concentration profile information is available [11,13]. Accordingly, different patches might deliver similar overall concentrations but the day-to-day oestradiol concentrations achieved might differ substantially, especially during the early period of patch application, when maximum concentrations are reached.…”

Section: Resultsmentioning

confidence: 99%

Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first‐line hormonal therapy in patients with locally advanced or metastatic prostate cancer

et al. 2008

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OBJECTIVE To assess the hormonal effects of Fem7® (Merck, KGaA, Darmstadt, Germany) 100 µg transdermal oestrogen patches on men undergoing first‐line androgen‐deprivation therapy for prostate cancer. PATIENTS AND METHODS PATCH is a multicentre, randomized, phase II trial for men with locally advanced or metastatic prostate cancer, comparing luteinizing hormone‐releasing hormone agonist therapy with oestrogen patches. To assess the dosing schedule for the patches, as this was the first time that this brand of patch had been used in men, and to reassure patients and participating clinicians, the Independent Data Monitoring Committee agreed to early release of hormonal data from this study. RESULTS Oestradiol, testosterone and prostate‐specific antigen (PSA) levels are presented for the first group of 14 patients who received the patches (with 1 withdrawal) and for whom there were ≥12 weeks of follow‐up by March 2007. After 12 weeks, testosterone levels (nmol/L) in eight of the 13 patients were <1.7, two were 1.7–2 and three were >2. The median (range) serum oestradiol levels was 442 (52.1–1542) pmol/L and all patients had a PSA response, with eight having a PSA level of <4 ng/mL. CONCLUSION These results confirm that oestrogen patches produce castrate levels of testosterone and concomitant PSA responses. They also highlighted the potential differences between different brands of oestrogen patches, and the need to monitor hormonal response, toxicity and efficacy until more experience with oestrogen patches for this clinical indication is obtained. The number of patches recommended in the PATCH study has now been increased.

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Section: Resultsmentioning

confidence: 99%

Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first‐line hormonal therapy in patients with locally advanced or metastatic prostate cancer

et al. 2008

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“…The isoflavones and their derivatives appear to be readily percutaneously bioavailable as is oestrogen in humans (32). However, it is not yet understood whether the isoflavone action is localized in the skin where the UV radiation-induced mediators of the inflammation and the immunosuppression have been identified, or whether the isoflavone has distant targets involved in the systemic regulation of these UV responses.…”

Section: Discussionmentioning

confidence: 99%

Isoflavonoid Compounds from Red Clover (Trifolium pratense) Protect from Inflammation and Immune Suppression Induced by UV Radiation¶

Widyarini

Spinks²,

Husband³

et al. 2001

Photochem Photobiol

125

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Isoflavones derived from many edible plants have been reported to possess significant antioxidant, estrogenic and tyrosine kinase inhibitory activity. Genistein has been found previously to provide protection from oxidative damage induced by UV radiation both in vitro and following dietary administration. We have therefore examined the potential of a number of isoflavones from red clover (Trifolium pratense) and some metabolically related compounds to offer protection from UV irradiation in hairless mice by topical application after UV exposure. We show that whereas the primary isoflavones, daidzein, biochanin A and formononetin, were inactive, 20 microM lotions of genistein and the metabolites equol, isoequol and the related derivative dehydroequol had powerful potential to reduce the inflammatory edema reaction and the suppression of contact hypersensitivity induced by moderate doses of solar-simulated UV radiation. For equol the protection was concentration dependent and 5 microM equol markedly reduced the UV-induced inflammation but abrogated the UV-induced immunosuppression. Equol protected similarly from immunosuppression induced by the putative epidermal mediator, cis-urocanic acid (UCA), indicating a potential mechanism of action involving inactivation of this UV-photoproduct. Since immunosuppression induced by both UV radiation and by cis-UCA appears to be an oxidant-dependent response our observations support the actions of these topically applied isoflavones and their metabolites as antioxidants. They also indicate that lotions containing equol, unlike topical UV sunscreens, more readily protect the immune system from photosuppression than from the inflammation of the sunburn reaction, even when applied after exposure, and thus such compounds may have a future role as sun-protective cosmetic ingredients.

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“…Secondly, no medication was available to induce sufficiently high and steady E 2 levels immediately after administration. The intended levels could only be reached by the use of multiple patches, which unfortunately would take 12 h to reach maximum levels (36). To induce high-E 2 levels on the day of the LH surge, it was decided to add an E 2 nasal spray.…”

Section: Discussionmentioning

confidence: 99%

“…1 Fem 7 patch increases E 2 levels to 600 pmol/l (36). Therefore, eight patches were applied on day of the positive LH test, which would give a C max of 4800 pmol/l after 16-24 h. When this C max and serial serum levels described earlier in a pharmacokinetic study (36) were taken into account, it could be expected to reach the following median E 2 levels: 4800 pmol/l on day LHC1, 2000 pmol/l on day LHC 2, 1800 on day LHC3, and 1500 pmol/l on day LHC4. As the patches were attached on the day of positive LH test, the E 2 levels on that same day would be slowly increasing (C max is only reached after 16-24 h).…”

Section: Justification Of Interventionsmentioning

confidence: 96%

The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women

Beckers¹,

Platteau²,

Eijkemans³

et al. 2006

eur j endocrinol

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Objective: The luteal phase after ovarian hyperstimulation for in vitro fertilization (IVF) is insufficient. Therefore, luteal phase supplementation is routinely applied in IVF. It may be postulated that premature luteolysis after ovarian hyperstimulation is due to supraphysiological steroid levels in the early luteal phase. In the present study, high doses of steroids are administered after the LH surge in normo-ovulatory volunteers in order to investigate whether this intervention gives rise to endocrine changes and a shortening of the luteal phase. Design: Randomized controlled trial. Methods: Forty non-smoking, normal weight women, between 18 and 37 years of age, with a regular menstrual cycle (24-35 days), received either high dosages of estradiol (E 2 ), progesterone (P), E 2 CP or no medication. Blood sampling was performed every other day from the day of the LH surge until LHC 14. Duration of the luteal phase and endocrine profiles were the main study outcomes. Results: Early luteal phase steroid concentrations achieved by exogenous administration were comparable with levels observed following ovarian hyperstimulation for IVF. No difference in the luteal phase length was observed comparing all groups. However, a significant decrease in LH levels could be observed 6 days after the mid-cycle LH surge (P!0.001) in women receiving P, resulting in accelerated decrease of inhibin A production by the corpus luteum (PZ0.001). Conclusion:The present intervention of high-dose steroid administration shortly after the LH surge failed to induce a premature luteolysis regularly in cyclic women. It seems that the induced transient suppression in LH allowed for a timely recovery of corpus luteum function. Other additional factors may be held responsible for the distinct reduction in luteal phase length observed after ovarian hyperstimulation for IVF.

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Pharmacokinetics of Fem7<sup>®</sup>, a Once-Weekly, Transdermal Oestrogen Replacement System in Healthy, Postmenopausal Women

Cited by 8 publications

References 21 publications

Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first‐line hormonal therapy in patients with locally advanced or metastatic prostate cancer

Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first‐line hormonal therapy in patients with locally advanced or metastatic prostate cancer

Isoflavonoid Compounds from Red Clover (Trifolium pratense) Protect from Inflammation and Immune Suppression Induced by UV Radiation¶

The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women

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