Menopause. 2004 Jan-Feb;11(1):11-33. Links
Treatment of menopause-associated vasomotor
symptoms: position statement of The North American Menopause Society.North American Menopause Society.
North American Menopause Society, Cleveland,
OH 44101, USA.
OBJECTIVE: To create an evidence-based
position statement regarding the treatment of vasomotor symptoms associated with menopause. DESIGN: The North American Menopause
Society (NAMS) enlisted clinicians and researchers acknowledged to be experts in the field of menopause-associated vasomotor
symptoms to review the evidence obtained from the medical literature and develop a document for final approval by the NAMS
Board of Trustees. RESULTS: For mild hot flashes, lifestyle-related strategies such as keeping the core body temperature cool,
participating in regular exercise, and using paced respiration have shown some efficacy without adverse effects. Among nonprescription
remedies, clinical trial results are insufficient to either support or refute efficacy for soy foods and isoflavone supplements
(from either soy or red clover), black cohosh, or vitamin E; however, no serious side effects have been associated with short-term
use of these therapies. Single clinical trials have found no benefit for dong quai, evening primrose oil, ginseng, a Chinese
herbal mixture, acupuncture, or magnet therapy. Few data support the efficacy of topical progesterone cream; safety concerns
should be the same as for other progestogen preparations. No clinical trials have been conducted on the use of licorice for
hot flashes. Among nonhormonal prescription options, the antidepressants venlafaxine, paroxetine, and fluoxetine and the anticonvulsant
gabapentin have demonstrated some efficacy for treating hot flashes and were well tolerated. Two antihypertensive agents,
clonidine and methyldopa, have shown modest efficacy but with a relatively high rate of adverse effects. For moderate to severe
hot flashes, systemic estrogen therapy, either alone (ET) or combined with progestogen (EPT) or in the form of estrogen-progestin
oral contraceptives, has been shown to significantly reduce hot flash frequency and severity. Clinical trials have associated
ET/EPT with adverse effects, including breast cancer, stroke, and thromboembolism. Several progestogens (both oral and intramuscular
formulations) have shown efficacy in treating hot flashes, including women with a history of breast cancer, although no definitive
data are available on long-term safety in these women. CONCLUSIONS: In women who need relief for mild vasomotor symptoms,
NAMS recommends first considering lifestyle changes, either alone or combined with a nonprescription remedy, such as dietary
isoflavones, black cohosh, or vitamin E. Prescription systemic estrogen-containing products remain the therapeutic standard
for moderate to severe menopause-related hot flashes. Recommended options for women with concerns or contraindications relating
to estrogen-containing treatments include prescription progestogens, venlafaxine, paroxetine, fluoxetine, or gabapentin. Clinicians
are advised to enlist women's participation in decision making when weighing the benefits, harms, and scientific uncertainties
of therapeutic options. Regardless of the management strategy adopted, treatment should be periodically reassessed as menopause-related
vasomotor symptoms will abate over time without any intervention in most women.
PMID: 14716179 [PubMed - indexed for MEDLINE]
Ann Intern Med. 2002 Nov 19;137(10):805-13.
Links
Comment in:
ACP J Club. 2003 Jul-Aug;139(1):21.
Complementary and alternative medicine
for menopausal symptoms: a review of randomized, controlled trials.Kronenberg F, Fugh-Berman A.
Rosenthal Center for Complementary and
Alternative Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, Box 75, New York, NY
10032, USA.
BACKGROUND: Women commonly use soy products,
herbs, and other complementary and alternative medicine (CAM) therapies for menopausal symptoms.
Randomized, controlled trials have evaluated the efficacy and short-term safety of these therapies. PURPOSE: To review randomized,
controlled trials of CAM therapies for menopausal symptoms in order to better inform practice
and guide future research. DATA SOURCES: Searches of MEDLINE for articles published from January 1966 through March 2002,
of the Alternative and Complementary Database (AMED) of the British Library for articles published from January 1985 through
December 2000, and of the authors' own extensive files. Search terms were hot flash/flush, menopause, and climacteric, combined
with phytoestrogens, alternative medicine, herbal medicine, traditional medicine, Traditional Chinese Medicine (TCM ), Ayurveda,
naturopathy, chiropractic, osteopathy, massage, yoga, relaxation therapy, homeopathy, aromatherapy, and therapeutic touch.
STUDY SELECTION: 29 randomized, controlled clinical trials of CAM therapies for hot flashes and other menopausal symptoms
were identified; of these, 12 dealt with soy or soy extracts, 10 with herbs, and 7 with other CAM
therapies. DATA EXTRACTION: Each author extracted information from half of the studies on the number of patients, study design,
outcome measures, and results; the other author then checked these results. DATA SYNTHESIS: Soy seems to have modest benefit
for hot flashes, but studies are not conclusive. Isoflavone preparations seem to be less effective than soy foods. Black cohosh
may be effective for menopausal symptoms, especially hot flashes, but the lack of adequate long-term safety data (mainly on
estrogenic stimulation of the breast or endometrium) precludes recommending long-term use. Single clinical trials have found
that dong quai, evening primrose oil, a Chinese herb mixture, vitamin E, and acupuncture do not affect hot flashes; two trials
have shown that red clover has no benefit for treating hot flashes. CONCLUSIONS: Black cohosh and foods that contain phytoestrogens
show promise for the treatment of menopausal symptoms. Clinical trials do not support the use of other herbs or CAM therapies. Long-term safety data on individual isoflavones or isoflavone concentrates are not available.
PMID: 12435217 [PubMed - indexed for MEDLINE]
Menopause. 2007 Jul 6;Publish Ahead of
Print [Epub ahead of print] Links
Vaginal, endometrial, and reproductive
hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor
symptoms: the Herbal Alternatives for Menopause (HALT) Study.Reed SD, Newton KM, Lacroix AZ, Grothaus LC, Grieco VS, Ehrlich
K.
From the 1Group Health Center for Health
Studies, Seattle, WA; Departments of 2Obstetrics and Gynecology
and 3Pathology, University of Washington
School of Medicine, Seattle,
WA; and 4Fred Hutchinson Cancer
Research Center, Public Health Sciences
Division, Seattle, WA.
OBJECTIVE:: To evaluate vaginal, endometrial,
and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT). DESIGN:: This was
a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms
per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical
plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or
menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3
and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum
estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline
and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared. RESULTS:: The five groups
did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group
had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal
bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the
herbal and placebo groups, whereas women in the HT group had a greater risk than those
in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone
and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point. CONCLUSION::
Black cohosh, used alone or as part of a multibotanical product with or without soy
dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.
PMID: 17667147 [PubMed - as supplied by
publisher]
Maturitas. 2007 Jun 20;57(2):195-204. Epub
2007 Feb 1. Links
The effects of black cohosh therapies on
lipids, fibrinogen, glucose and insulin.Spangler L, Newton KM, Grothaus LC, Reed SD, Ehrlich K, LaCroix AZ.
Center for Health Studies, Group Health,
Seattle, WA 98101,
USA. spangler.l@ghc.org
OBJECTIVE: Black cohosh (Actaea racemosa)
is an herb commonly used to treat menopausal symptoms. Little is known about its effect on other physiologic parameters that
could result in untoward events. This study examines the effect of black cohosh on lipids, fibrinogen, glucose and insulin.
METHODS: Three hundred and fifty-one, 45-55 years old, peri or post-menopausal women experiencing vasomotor symptoms participated
in a 3-month, double blind trial with randomization to: (1) black cohosh (160 mg daily); (2) multibotanical including black
cohosh (200 mg daily); (3) multibotanical plus soy diet counseling; (4) conjugated equine estrogen .625 mg, with or without
medroxyprogesterone acetate 2.5mg daily, for women with or without a uterus, respectively; (5) placebo. Baseline and month
3 total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), triglyceride,
insulin, glucose, and fibrinogen serum concentrations were measured in 310 women. Baseline information was also collected
on medical history, demographic characteristics, and diet. RESULTS: There were no statistically significant differences in
the adjusted mean change from baseline to 3 months between the herbal groups and placebo in total cholesterol, LDL, HDL, triglycerides,
glucose, and insulin. Adjusted fibrinogen levels appear to increase in the multibotanical treatment group in comparison with
the other herbal groups and placebo overall (P = .02), but there was no statistically significant difference in the pairwise
test against placebo (P = .11). CONCLUSIONS: Black cohosh containing therapies had
no demonstrable effects on lipids, glucose, insulin or fibrinogen.
PMID: 17275226 [PubMed - indexed for MEDLINE]
J Clin Oncol. 2006 Jun 20;24(18):2836-41.
Links
Phase III double-blind, randomized, placebo-controlled
crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1.Pockaj BA, Gallagher JG, Loprinzi CL,
Stella PJ, Barton DL, Sloan JA, Lavasseur BI, Rao RM, Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, Richelson E, Fauq AH.
Mayo Clinic and Mayo Foundation, Rochester, MN 55905,
USA.
PURPOSE: Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment.
Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. METHODS:
A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh
(1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash
diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning
points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period.
RESULTS: Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different
by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth
treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency
was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion
of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients
preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. CONCLUSION: This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.
PMID: 16782922 [PubMed - indexed for MEDLINE]
Maturitas. 2005 Aug 16;51(4):397-404. Epub
2004 Dec 10. Links
Cimicifuga racemosa dried ethanolic extract
in menopausal disorders: a double-blind placebo-controlled clinical trial.Frei-Kleiner S, Schaffner W, Rahlfs VW, Bodmer Ch,
Birkhäuser M.
Institute
of Pharmaceutical Biology, University of
Basel, Switzerland. susanne@frei-kleiner.ch
OBJECTIVES: To compare the efficacy and
safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints. METHODS: A multicenter, randomized,
placebo-controlled, double-blind, parallel group study was conducted in 122 menopausal women (intention-to-treat population)
with > or =3 hot flashes a day, treated over 12 weeks. Two main efficacy measures - weekly weighted score of hot flashes
and Kupperman Index - and secondary efficacy variables, e.g. Menopause Rating Scale, were defined. Routine safety laboratory
parameters and adverse events were documented. RESULTS: The primary efficacy analysis showed no superiority of the tested
black cohosh extract compared to placebo. However, in the subgroup of patients with a Kupperman Index> or =20 a significant
superiority regarding this index could be demonstrated (P<0.018). A decrease of 47% and 21% was observed in the black cohosh
and placebo group, respectively. The weekly weighted scores of hot flashes (P<0.052) and the Menopause Rating Scale (P<0.009)
showed similar results. Prevalence and intensity of the adverse events did not differ in the two treatment groups. CONCLUSIONS:
The results indicate a superiority of the tested Cimicifuga racemosa extract compared
to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index > or
=20, but not in the intention-to-treat population as a whole.
PMID: 16039414 [PubMed - indexed for MEDLINE]
Maturitas. 2003 Mar 14;44 Suppl 1:S67-77.
Links
The Cimicifuga preparation BNO 1055 vs.
conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers.Wuttke W,
Seidlová-Wuttke D, Gorkow C.
Department of Clinical and Experimental
Endocrinology, University of Göttingen,
Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
ufkendo@med.uni-goettingen.de
OBJECTIVES: In the present study, therapeutic
effects of the Cimicifuga racemosa preparation CR BNO 1055 (Klimadynon/Menofem) on
climacteric complaints, bone metabolism and endometrium will be compared with those of conjugated estrogens (CE) and placebo.
The question whether CR BNO 1055 contains substances with selective estrogen receptor modulator (SERM) activity will be investigated.
METHODS: Sixty-two evaluable postmenopausal women were included in the double-blind, randomized, multicentre study, and treated
either with CR BNO 1055 (daily dose corresponding to 40 mg herbal drug), 0.6 mg CE, or matching placebo, for 3 months. Menopausal
symptoms were assessed by the menopause rating scale (MRS) and a diary. Levels of CrossLaps (marker of bone degradation) were
determined by ELECSYS system and bone-specific alkaline phosphatase (marker of bone formation) by an enzymatic assay. Endometrial
thickness was measured via transvaginal ultrasound; vaginal cytology was also studied. The primary efficacy criterion was
the change from baseline to end point in the MRS. Change from baseline was analyzed for the secondary variables too. RESULTS:
CR BNO 1055 proved to be equipotent to CE and superior to placebo in reducing climacteric complaints. Under both verum preparations,
beneficial effects on bone metabolism have been observed in the serum. CR BNO 1055 had no effect on endometrial thickness,
which was significantly increased by CE. Vaginal superficial cells were increased under CE and CR BNO 1055 treatment. CONCLUSION:
The results concerning climacteric complaints and on bone metabolism indicate an equipotent
effect of CR BNO 1055 in comparison to 0.6 mg CE per day. It is proposed that CR BNO 1055 contains substances with SERM
activity, i.e. with desired effects in the brain/hypothalamus, in the bone and in the vagina, but without exerting uterotrophic
effects.
PMID: 12609561 [PubMed - indexed for MEDLINE]
Yonsei Med J. 2007 Apr 30;48(2):289-94.
Links
Black cohosh and St. John's wort (GYNO-Plus)
for climacteric symptoms.Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho
SH, Hwang JY, Park JH.
Department of Obstetrics and Gynecology,
Yonsei University College
of Medicine, 134 Sinchon-Dong, Seodaemun-Gu, Seoul, Korea.
PURPOSE: This study was conducted
to investigate the efficacy of black cohosh (Cimicifuga racemosa) and St. John's
wort (Hypericum perforatum) in women with climacteric symptoms, and to assess their effects on vaginal atrophy, hormone levels,
and lipid profiles. MATERIALS AND METHODS: In this double-blind randomized, placebo-controlled, multicenter study, 89 peri-
or postmenopausal women experiencing climacteric symptoms were treated with St. John's wort and black cohosh extract (Gynoplus),
Jin-Yang Pharm., Seoul, Korea) or a matched placebo for 12 weeks. Climacteric complaints were evaluated by the Kupperman Index
(KI) initially and at 4 and 12 weeks following treatment. Vaginal maturation indices, serum estradiol, FSH, LH, total cholesterol,
HDL- cholesterol, LDL-cholesterol, and triglyceride levels were measured before and after treatment. From the initial 89 participants,
77 completed the trial (42 in the Gynoplus group, 35 in the placebo group). RESULTS: Baseline characteristics were not significantly
different between the two groups. Mean KI scores and hot flushes after 4 and 12 weeks were significantly lower in the Gynoplus
group. Differences in superficial cell proportion were not statistically significant. HDL levels decreased in the control
group from 60.20 +/- 16.37 to 56.63 +/- 12.67, and increased in the Gynoplus group from 58.32 +/- 11.64 to 59.74 +/- 10.54;
this was statistically significant (p=0.04). CONCLUSION: Black cohosh and St. John's wort combination was found to be effective in alleviating
climacteric symptoms and might provide benefits to lipid metabolism.
PMID: 17461529 [PubMed - indexed for MEDLINE
Maturitas. 2007 Aug 20;57(4):405-14. Epub
2007 Jun 21. Links
Black cohosh with or without St. John's
wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study.Briese V, Stammwitz
U, Friede M, Henneicke-von Zepelin HH.
Department of Gynecology at the Universitaets
Klinikum Suedstadt, Suedring 81, D-18059 Rostock, Germany.
OBJECTIVES: To evaluate usage pattern,
effectiveness and safety of Black cohosh alone or in fixed combination with St. John's
wort on menopausal symptoms in general clinical practice. METHOD: Prospective, controlled open-label observational study of
6141 women at 1287 outpatient gynecologists in Germany.
Subjects were treated with recommended doses of study therapies, with treatment chosen by the participating physicians. Patients
were followed up for 6 months, optionally 12 months. The primary effectiveness variable was Menopause Rating Scale (MRS) subscore
PSYCHE at Month 3 evaluated by ANCOVA. RESULTS: The treatment groups were comparable at baseline, excepting the main MRS score
and the PSYCHE score (monotherapy: 0.31+/-0.22; combination therapy: 0.42+/-0.23). Reductions from baseline were seen with
both regimens for all variables. The changes in the primary variable remained significantly different between groups (p<0.001)
when adjusted for differences at baseline with the combination therapy being superior: from 0.37 (adjusted) to 0.25 (95% CI:
0.24-0.25) and 0.23 (95% CI: 0.22-0.23) at Month 3 in the monotherapy and combination-therapy groups, respectively. The improvement
by both therapies was maintained at 6 and 12 months. The rate of possibly treatment-related adverse events was 0.16%, all
non-serious. CONCLUSION: The results support the effectiveness and tolerability profiles of two Black cohosh-based therapies
for menopausal symptoms in general practice. They were used differentially: the monotherapy for neurovegetative symptoms,
the combination for patients with more pronounced mood complaints. The fixed combination
of Black cohosh and St. John's wort was superior to Black
cohosh alone in alleviating climacteric mood symptoms.
PMID: 17590291 [PubMed - indexed for MEDLINE]
Br J Dermatol. 2005 Sep;153(3):626-34.
Links
Erratum in:
Br J Dermatol. 2005 Nov;153(5):1092. Schmidt,
B [corrected to Schmidt, JB].
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, Hönigsmann H, Farokhnia S, Schmidt JB.
Division of Special and Environmental Dermatology,
Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. gregor.holzer@meduniwien.ac.at
BACKGROUND: For many years topical progesterone
has been prescribed by gynaecologists as an antiageing and skin-firming treatment, without any clinical scientific evidence
of its effects, tolerability and safety when applied to skin. OBJECTIVES: To evaluate the influence of 2% progesterone cream
on function and texture of the skin in peri- and postmenopausal women. METHODS: A double-blind, randomized, vehicle-controlled
study was conducted in 40 subjects. Objective methods for measuring skin elasticity, epidermal hydration and skin surface
lipids, clinical monitoring and self-assessment, and determination of blood hormone levels (luteinizing hormone, follicle-stimulating
hormone, oestrogen and progesterone) were used to determine effects and side-effects of this treatment at four visits over
a 16-week period. RESULTS: The study demonstrated a significant (P < or = 0.05) increase of the elastic skin properties
in the treatment group, as demonstrated by objective measurements of three skin elasticity parameters, whereas in the control
group no such effect was observed. This effect in the treatment group was further paralleled by the results of the clinical
monitoring, where the 2% progesterone cream yielded consistent superiority over vehicle in counteracting different signs of
ageing in the skin of peri- and postmenopausal women. Clinical monitoring showed a greater reduction in wrinkle counts (29.10%
vs. 16.50%) and wrinkle depth (9.72% vs. 7.35%) around the right eye, a greater decrease in nasolabial wrinkle depth (9.72%
vs. 6.62%) and a significantly higher (P < 0.05) increase in skin firmness (23.61% vs. 13.24%) in the treatment group.
Epidermal hydration and skin surface lipids did not change significantly in either group during the study. Progesterone was
well absorbed in the systemic circulation: mean blood levels rose minimally, but statistically significantly (P = 0.001),
by 0.53 ng mL(-1). No serious side-effects of the treatment were observed. CONCLUSIONS: The results of this study demonstrate
that topical 2% progesterone acts primarily in increasing elasticity and firmness in the skin of peri- and postmenopausal
women. These effects in combination with good tolerability make progesterone a possible treatment agent for slowing down the
ageing process of female skin after onset of the menopause.
PMID: 16120154 [PubMed - indexed for MEDLINE]
J Clin Pharmacol. 2005 Jun;45(6):614-9.
Links
Over-the-counter progesterone cream produces
significant drug exposure compared to a food and drug administration-approved oral progesterone product.Hermann AC, Nafziger
AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr.
Department of Medicine, Bassett Healthcare,
Cooperstown, New York, USA.
Progesterone products are available in
prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design,
the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation
at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone
capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase),
whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total
progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing
the cream to oral capsules (median AUC(0-24) 12.5 ng x h/mL vs 10.5 ng x h/mL, respectively; P = .81). In light of the potential
risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available
OTC.
PMID: 15901742 [PubMed - indexed for MEDLINE]
Arch Otolaryngol Head Neck Surg. 1999 Oct;125(10):1091-8.
Links
Use of topical ascorbic acid and its effects
on photodamaged skin topography.Traikovich SS.
Beeson Aesthetic Surgery Institute, Carmel, Ind., USA.
AJLively@POL.NET
OBJECTIVE: To determine the efficacy of
topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted
image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.
DESIGN: A 3-month, randomized, double-blind, vehicle-controlled study. SETTING: Facial plastic surgery private practice. PATIENTS:
Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were
in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis. INTERVENTION:
Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the
active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the
vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned
hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved
in analyzing skin replicas. MAIN OUTCOME MEASURES: Specific clinical parameters were evaluated and graded on a 0- to 9-point
scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria.
Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly
improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved,
slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration,
itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views
to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was
performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens.
Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect
surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document
pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.
RESULTS: Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows
north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the
Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical
assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness,
coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically
significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant
improvement, active treatment 57.9% greater than control. CONCLUSIONS: A 3-month daily regimen of topical ascorbic acid provided
objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method
for quantification of the skin surface texture changes.
PMID: 10522500 [PubMed - indexed for MEDLINE]
