progesterone cream
Effects and side effects of 2%-progesterone cream on the skin of peri- and postmenopausal women: Results from a double blind, vehicle-controlled, randomized study.

Holzer G, Riegler E, Honigsmann H, Schmidt J.

Division of Special and Environmental Dermatology, University of Vienna Medical School, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.

Background: Since many years topical progesterone has been prescribed by gynecologists as an anti-aging and skin firming treatment, without any clinical scientific evidence of its effects, tolerability and its safety when topically applied to skin. Objective: The objective of this study was to evaluate the influence of 2%-progesterone cream on the functions and texture of the skin in the peri- and postmenopause. Methods: A double blind, randomized, vehicle controlled study was conducted in 40 subjects. Clinical monitoring, subjective self assessment, objective measurement methods of skin elasticity, epidermal hydration and skin surface lipids and the determination of blood hormone levels (LH, FSH, estrogen, and progesterone) were used to determine effects and side effects of this treatment at four visits during 24 weeks. Results: The study demonstrated consistent superiority of 2%-progesterone cream over vehicle in counteracting different signs of aging in the skin of peri- and postmenopausal women. Clinical monitoring observed higher reductions in wrinkle counts (-29,10% vs. 16,50%) and wrinkle depth (-9,72 vs. -7,35%) around the right eye, higher decrease in nasolabial wrinkle depth (-9,72% vs. -6,62%) and a significantly higher (p = 0,031) improvement of skin firmness (23,61% vs.13,24%) in the treatment group. 2%-progesterone cream also yielded significant improvements (p < 0,05) in the objective measurement of different parameters of skin viscoelasticity and elasticity compared to the vehicle group. Epidermal hydration and skin surface lipids did not change significantly in both groups during the study. Progesterone was well absorbed in the systemic circulation, mean blood levels rose minimally, but statistically significant (p = 0,001) by 0,53 ng/nl. No serious side effects of the treatment were observed. Conclusions: The results of this study demonstrate that topical 2%-progesterone acts primarily in a skin firming and elasticity improving manner on hormone deficient skin of the peri- and postmenopause. These effects in combination with good tolerability make progesterone a possible treatment agent in slowing down the aging process of the female skin after onset of menopause.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15679603&dopt=Abstract progesterone, progesterone cream



progesterone cream
Anesthetic effects of progesterone are undiminished in progesterone receptor knockout mice.

Reddy DS, Apanites LA.

Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA. samba_reddy ncsu.edu

Progesterone has sedative and anesthetic effects but the underlying molecular mechanisms remain unclear. The two possible mechanisms by which progesterone affects the function of the brain include binding to intracellular progesterone receptors (PR) and metabolism to GABA(A) receptor-modulating neurosteroids. In this study, PR knockout (PRKO) mice were used as model to study the role of PRs in the anesthetic activity of progesterone. The progesterone-induced anesthetic activity was undiminished in female PRKO mice (ED50, 172 mg/kg) as compared to their wild-type littermates (ED50, 167 mg/kg). The progesterone-induced anesthetic activity was highly correlated with increased plasma allopregnanolone levels. Pretreatment of PRKO mice with the 5alpha-reductase inhibitor finasteride significantly reduced the progesterone-induced anesthetic activity. Allopregnanolone also evoked dose-dependent anesthetic activity in PRKO mice, which was similar to those of wild-type mice. Thus, the anesthetic activity of progesterone is not mediated by its interaction with PRs. The neurosteroid allopregnanolone partially mediates the anesthetic activity of progesterone by potentiation of GABA(A) receptor function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15680344&dopt=Abstract progesterone, progesterone cream



progesterone cream
Identification of a 71 kDa protein as a putative non-genomic membrane progesterone receptor in boar spermatozoa.

Jang S, Yi LS.

Department of Biological Science and the Institute for Basic Science, Sungkyunkwan University, Suwon, 440-746, Korea.

A putative non-genomic progesterone receptor was identified by Western blot analysis from the membrane fraction but not the cytosolic fraction of boar spermatozoa using monoclonal antibody (mAb) C-262. When the membrane and the cytosolic fractions of boar liver, kidney, uterus and spermatozoa were analyzed with mAb C-262, protein bands with molecular masses of 86 and 120 kDa were detected from the cytosolic fraction of the uterus, whereas a 71 kDa protein was detected from the membrane fraction of spermatozoa. Apparently, while the 86 and 120 kDa proteins from the uterus correspond to the genomic progesterone receptor isoforms A and B in boar, the 71 kDa protein of the sperm membrane fraction seems to be a novel membrane-associated progesterone receptor. Ligand blot assay of the membrane and the cytosolic fractions of boar spermatozoa performed with peroxidase-conjugated progesterone revealed that only the 71 kDa membrane protein binds specifically to progesterone, reinforcing the results obtained from the Western blot analysis. Also ligand blot assays performed in the presence of mAb C-262 demonstrated that mAb C-262 inhibited progesterone binding to the 71 kDa protein in a dose-dependent manner. Ligand blot assays performed in the presence of free progesterone, RU486 or estrogen revealed that binding of peroxidase-conjugated progesterone to the 71 kDa protein was inhibited by free progesterone and RU486 in a dose-dependent manner but not by estrogen, which further confirms that progesterone binds to the 71 kDa protein specifically. Furthermore, the progesterone-induced acrosome reaction was inhibited by mAb C-262 in a dose-dependent manner. These results strongly imply that spermatozoa possess a progesterone receptor in a membrane-bound form and can be influenced by progesterone via non-genomic progesterone receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15684349&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone increases blood pressure in spontaneous gestational hypertension in rats.

Sharkey LC, Kirchain S, McCune SA, Simpson GI, Archambault EZ, Boatright NK, Hicks E, Fray J.

Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts, USA.

BACKGROUND: Gestational hypertensive disorders are a leading cause of maternal mortality in the US, accounting for up to 10% of these deaths. During pregnancy, a new rat model (SHHF rat) has been shown to develop spontaneous hypertension with increases of more than 40 mm Hg systolic blood pressure (BP), which resolves after delivery, and which lead us to ask whether the hypertension may be triggered by increased levels of progesterone in these rats. METHODS: To test this hypothesis, groups of SHHF rats were treated with progesterone (PROG), estrogen (EST), or progesterone and estrogen (PROG+EST) that correspond to levels that occur during pregnancy. Control (CON) rats received saline-filled implants and pseudopregnancy was induced in another group. Wistar-Kyoto rats served as controls for SHHF rats. RESULTS: By experimental day 3, progesterone caused a significantly higher systolic BP, similar to pseudopregnancy and to previously reported values during pregnancy in this strain. Blood pressure in SHHF rats given estrogen was not significantly different. RU486 reversibly prevented the increase in BP induced by progesterone. CONCLUSIONS: These results indicate that an anomalous response to progesterone causes dramatic increases in BP in SHHF rats during a short period of time, in contrast to the decrease in BP in response to progesterone, which has been reported in other rat models of hypertension. An abnormal pressor response to progesterone should be considered a potential mechanism contributing to the development of hypertension during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15691615&dopt=Abstract progesterone, progesterone cream



progesterone cream
What is the 'ideal' duration of progesterone supplementation before the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement protocols?

Nawroth F, Ludwig M.

Endokrinologikum Hamburg, Zentrum fur Hormon- und Stoffwechselerkrankungen, Reproduktionsmedizin und Gynakologische Endokrinologie, Lornsenstrasse 4-6, 22767 Hamburg, Germany.

Different studies dealing with the start of progesterone supplementation in assisted reproduction treatment cycles have shown that the problem apparently is the correct timing. We therefore would like to discuss the data on: (i) the start of progesterone replacement in oocyte donation programmes; (ii) the start of progesterone replacement in frozen-thawed hormone-supplemented cycles; (ii) the problem of too early a rise of progesterone in fresh IVF cycles as a model of too early an administration of progesterone; and (iv) the benefit of high progesterone levels on the day of embryo transfer in fresh IVF cycles. From the data reviewed in this paper it seems to be appropriate to start progesterone administration before transfer in oocyte donation programmes as well as transfer of cryopreserved/thawed cells as soon as the endometrium is developed sufficiently (>/=8 mm, trilaminar pattern), and to perform the embryo transfer not before day 3-4 of progesterone treatment, i.e. embryo development on day 2-3. Studies dealing with the influence of too early a rise of progesterone in fresh IVF cycles have shown different results. In fact high progesterone levels seem to reflect a high response but not a lower probability of conception. Furthermore, high progesterone levels on the day of embryo transfer in fresh IVF cycles could lower myometrial contractility and therefore increase implantation rates. Since the experience from oocyte donation programes shows the benefit of a longer preparation time using progesterone, and high progesterone levels seem to have a benefit during embryo transfer, this would suggest extending progesterone administration before transfer. However, we have to find the optimal individual transfer protocol after mock cycles, for example with pinopode detection or other methods applicable in routine IVF programmes. We need more studies to be sure whether reproductive outcome after transfer of cryopreserved-thawed cells in estrogen/progesterone supplement cycles is influenced by the duration of progesterone pretreatment. If this is so, we must look for practicable methods to modify the protocols according to the individual patient, the embryonic developmental stage during transfer and other variables.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15695314&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone enhances the tocolytic effect of ritodrine in isolated pregnant human myometrium.

Chanrachakul B, Pipkin FB, Warren AY, Arulkumaran S, Khan RN.

Academic Division of Obstetrics and Gynaecology, Derby City General Hospital, University of Nottingham, Derby, DE22 3DT, United Kingdom.

OBJECTIVE: To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility. STUDY DESIGN: Isometric tension recordings were performed under physiologic conditions on isolated myometrial strips taken from low-risk term pregnant women undergoing elective cesarean section. Cumulative effects of natural progesterone (10 (-11) to 10 (-5) mol/L) on oxytocin-induced myometrial contractility were evaluated. Contractile activity following ritodrine exposure was also investigated in myometrium pretreated with natural progesterone. RESULTS: Natural progesterone alone exerted a concentration-dependent relaxant effect on myometrial contractions. The concentration-response curve for ritodrine from natural progesterone pretreated myometrium was shifted to the left with a significant reduction ( P < .01) of 50% of the maximal response, contraction amplitude ( P < .05), and frequency ( P < .05). However, there was no significant difference in the mean maximal inhibition achieved ( P = .95). CONCLUSION: Natural progesterone increased the relaxant effect of ritodrine by reducing 50% of the maximal response, amplitude, and frequency of myometrial contraction, most likely through nongenomic actions. These results suggest that natural progesterone may be beneficial for preventing preterm birth in a low-risk population.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15695987&dopt=Abstract progesterone, progesterone cream



progesterone cream
Oxytocin-induced prostaglandin E2 (PGE2) synthesis is regulated by progesterone via oxytocinase in Ishikawa cells.

Kotani Y, Iwase A, Ando H, Mizutani S.

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Cell-surface oxytocinase inactivates oxytocin and regulates oxytocin stimulation. We reported that oxytocinase in human endometrial epithelial cells was secreted from the cell membrane in the mid-secretory phase and disappeared from the cell surface. On the other hand, the production in human endometrium of prostaglandins, which play important roles in the reproductive process, has been reported to be upregulated by oxytocin. We investigated whether progesterone affects cell-surface oxytocinase and oxytocin-induced prostaglandin E2 (PGE2) production in vitro. Progesterone induced secretion of oxytocinase into the culture medium, which resulted in a decrease in cell-surface oxytocinase. Production of PGE2 was increased slightly by oxytocin without progesterone, and significantly with progesterone. The inhibition of oxytocinase activity by amastatin had a similar effect to the loss of cell-surface oxytocinase caused by progesterone. It is therefore likely that the cell-surface oxytocinase of endometrial epithelial cells modified by progesterone plays an important role in the function of the human endometrium through PGE2.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15702431&dopt=Abstract progesterone, progesterone cream