Quantification of the adverse effect of ethinylestradiol containing oral contraceptive pills when used in conjunction with growth hormone replacement in routine practice.

OBJECTIVE: Oestrogen antagonizes the action of growth hormone (GH). For women with combined GH and oestrogen deficiency, transdermal oestradiol is more favourable in this regard compared to oral oestradiol. Oral contraceptive pills containing ethinylestradiol (EE) are commonly used in young women with GHD and there is little information on the impact of this form of oestrogen. DESIGN: A case note review of women with growth hormone deficiency (GHD) attending a tertiary endocrine clinic comparing the dose of GH and serum insulin-like growth factor 1 concentrations and the type of exogenous oestrogen. METHODS: All women with GHD between the ages of 18 and 47 attending University College London Hospitals (UCLH) were included and grouped according to type of oestrogen replacement. Weight, GH dose and serum IGF-I concentrations were recorded at 121 visits in 88 women. RESULTS: The daily dose of GH was significantly higher and the GH responsivity was significantly lower in the EE group compared to those taking no oestrogen and transdermal oestrogen. The additional cost of GH for women using EE compared to transdermal oestradiol was £6016 per patient per year. Effectiveness of GH improved in all women changing from EE to another form of oestrogen. CONCLUSION: Use of oral contraceptive pills containing EE should be avoided in women receiving treatment with GH. Alternative options include oral or transdermal hormone replacement therapy (HRT) preparations for those that require oestrogen replacement or a progesterone-based regimen for contraceptive purposes.

Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources.

BACKGROUND AND OBJECTIVE: Acne is a common dermatologic condition that extends into middle age, particularly among women, and is associated with substantial healthcare resource utilization. Drospirenone (DRSP), a synthetic progestin, has anti-androgenic activity, and women using DRSP 3.0 mg/ethinyl estradiol (EE) 0.02 mg as a 24/4 regimen (DRSP/EE-24/4) for contraception also may use it for treatment of moderate acne. The study used a US national healthcare database to assess acne-related healthcare resource utilization among women aged 18-45 years before (pre-index) and after (post-index) initiation of DRSP/EE-24/4. METHODS: Resource utilization and costs were evaluated by age group (18-25, 26-35, or 36-45 years) and by type of acne medication (systemic antibiotic, topical, or anti-androgen). RESULTS: Data for 1340 women were evaluated. Overall, drug costs, medical costs, and total costs were decreased by 38%, 37%, and 37%, respectively (p<0.0001 for all) between the pre-index and post-index periods; significant differences were evident across age groups and acne medication categories. Total costs were significantly decreased for patients (41%) and healthcare plans (36%; p<0.0001 for both) overall and across age groups and drug classes. Acne-related claims and number of days using acne medication were reduced (by 37% each; p<0.0001 for both). STUDY LIMITATIONS: The study was retrospective in design and had a limited follow-up period. Database limitations restricted assessment of medication compliance and adherence. CONCLUSION: DRSP/EE-24/4 use was associated with substantial reductions in acne-related healthcare resource utilization, and reductions occurred regardless of age or type of acne medication. DRSP/EE-24/4 therefore represents a cost-effective option for the treatment of acne among women using DRSP/EE-24/4 for oral contraception.

Oral estroprogestin: an alternative low cost therapy for women with postoperative persistent acromegaly?

Oral estrogens reduce GH-induced IGF-1 production and preliminary studies have shown that adjuvant estroprogestin (EP) therapy with octreotide LAR may control disease activity in some female patients who are partially responsive to octreotide LAR. Our aim was to verify if EP alone or in combination with octreotide LAR can achieve remission of acromegaly in selected cases of patients uncontrolled by surgery. Eleven women with persistent active acromegaly following surgery participated in this unblinded open label pilot study. Their mean age was 49.8 ± 4.3 years. Two patients were drug naïve, two patients had stopped octreotide LAR because of intolerance and seven were treated with octreotide LAR. The patients received either EP (EP pill, 20 µg ethinylestradiol, 100 µg levonorgestrel) alone (4 patients) or added to octreotide LAR (7 patients). Fasting GH, IGF-1, glucose, HDL- and LDL-cholesterol, and triglycerides were measured at baseline and at last visit. MRI was controlled at baseline and at last visit. Duration of estrogen treatment was 3.1 ± 0.5 years. Serum IGF-1 levels were normalized in 8/11 patients (73%). Serum GH concentrations did not change significantly during treatment (11.6 ± 5.6 µg/L prior to EP vs 5.5 ± 1.2 µg/L following EP). In patients treated with EP alone, remission was achieved in 2/4 patients (IGF-1 percentages of the upper limit of normal age-matched range (%ULN): 211 ± 40% before EP compared to 95 ± 15% after EP, P = 0.028). In the seven patients treated by EP added to octreotide LAR, remission was achieved in 6 patients (IGF-1%ULN: 158 ± 9% before EP compared to 86 ± 4% after EP, P = 0.0003). Glucose and cholesterol levels were unchanged by EP treatment (data not shown). MRI did not show any evidence of tumour progression with EP in patients who had a tumour remnant. In conclusion, oral estrogen treatment appears to normalize serum IGF-1 concentrations in over 70% of women with acromegaly uncured by surgery irrespective of their sensitivity to octreotide LAR. We suggest that estrogens may be a temporary cost-effective and safe treatment for women with postoperative persistent acromegaly.

A randomized controlled trial of a low-dose combined oral contraceptive containing 3 mg drospirenone plus 20 microg ethinylestradiol in the treatment of acne vulgaris: lesion counts, investigator ratings and subject self-assessment.

OBJECTIVE: To assess the efficacy of a combined oral contraceptive (COC) containing 3 mg drospirenone (drsp) plus 20 microg ethinylestradiol (EE) administered in 24 days of active treatment followed by a four-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. METHODS: Healthy females (14-45 years old) with moderate facial acne were randomized to 3 mg drsp/20 microg EE 24/4 (n = 270) or placebo (n = 268) for six cycles. The secondary efficacy variables measured included change from baseline to endpoint (cycle 6) in individual lesion count for nodules, papules, pustules, open and closed comedones. RESULTS: There were significantly greater reductions in individual lesion counts from baseline to endpoint in the 3 mg drsp/20 microg EE group than in the placebo group (P < 0.05 from parametric model). CONCLUSION: The 3 mg drsp/20 microg EE COC administered in a 24/4 regimen significantly reduced acne lesions.

A combined oral contraceptive containing 3-mg drospirenone/ 20-microg ethinyl estradiol in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled study evaluating lesion counts and participant self-assessment.

This study compared the efficacy of a low-dose combined oral contraceptive (COC) containing 3-mg drospirenone and 20-microg ethinyl estradiol (3-mg DRSP/20-microg EE) administered in a 24-day active pill/4-day inert pill (24/4) regimen and placebo in women with moderate acne vulgaris during 6 treatment cycles. A total of 534 participants were randomized and dispensed study medication (n = 266 [3-mg DRSP/20-microg EE 24/4 regimen COC group]; n = 268 [placebo group]). Women of reproductive age were eligible for inclusion in the study. Treatment with the 3-mg DRSP/20-microg EE 24/4 regimen COC was associated with a greater reduction from baseline to end point in individual lesion counts (papules, pustules, open and closed comedones) compared with placebo. The mean nodule count remained essentially constant throughout the study and was low in both treatment groups. There was a significantly higher probability that a participant had an improved assessment on the investigator's overall improvement rating scale (odds ratio [OR], 4.02; 95% CI [confidence interval], 2.29-7.31; P < .0001) and participant's overall self-assessment rating scale (OR, 2.82; 95% CI, 1.60-5.13; P = .0005) in the 3-mg DRSP/20-microg EE 24/4 regimen COC group than in the placebo group. The COC 3-mg DRSP/20-microg EE 24/4 regimen is a suitable option for women with moderate acne vulgaris who require contraception.

Homeostasis model assessment-insulin resistance (HOMA-IR), a key role for assessing the ovulation function in polycystic ovary syndrome (PCOS) patients with insulin resistance.

According to our research, we evaluated that for the ovulation function in polycystic ovary syndrome (PCOS) with IR, Homeostasis model assessment-insulin resistance (HOMA-IR) is a clinic , simple and practical and sensitive Index for assessing the ovualtion failure. Meanwhile, after anti-IR treatment, HOMA-IR is also a reliable and simple for accessing the recoverying ovulation function.

Assessment, diagnosis and treatment of a patient with hirsutism.

BACKGROUND: A 20-year-old woman presented with excess facial and body hair, which she had noticed for the first time after her menarche and which had gradually worsened since then. In addition, the patient's menstrual cycles had always been irregular. Her family history revealed that her mother also had a history of excess body hair. Among the patient's family members there was no other history of chronic diseases, including type 2 diabetes. She denied taking any regular medications and had been shaving and waxing regularly to remove the excess hair. On examination, the patient was a lean woman with normal vital signs. Prominent coarse hair was noted over her upper lip, chin, lower abdomen, lower back and upper legs. The remainder of the physical examination was unremarkable. INVESTIGATIONS: Physical examination, and investigations that included a transabdominal pelvic ultrasound scan and measurement of TSH, prolactin, 17-hydroxyprogesterone and total testosterone levels. DIAGNOSIS: Hirsutism associated with polycystic ovary syndrome. MANAGEMENT: The patient was treated with cyproterone acetate 2 mg/day and ethinylestradiol 0.035 mg/day in combination with spironolactone 100 mg/day as well as with laser hair removal. The patient's symptoms had improved considerably after 1 year of treatment. A cardiometabolic risk assessment, including a standard oral glucose tolerance test and a lipid profile before and after treatment, revealed normal fasting and 2 h plasma glucose levels both at baseline and after 12 months, and a low-normal HDL-cholesterol level that returned to normal after 12 months.

[Assessment of efficacy of Diane-35 in androgenetic feminine alopecia]. / Ocena skutecznosci Diane-35 w aspekcie klinicznym i trichologicznym w lysieniu androgenowym kobiet.

The aim of the study was to carry out clinical and trichological examination (trichogram and assessment of hair loss) before and after therapy in 25 women aged 31-35 years with androgenetic alopecia. Diane-35 was given over 6-9 months once a day in a dose of 1 coated tablet beginning the therapy on the first day of menstrual cycle. After the administration of a whole package (1 blister) the drug was paused for 7 days which resulted in the occurrence of menorrhoea. The study showed that Diane-35 used for 6-9 months decreases clearly the loss of hair, hair thinning and seborrhoea.

Economic evaluation of norethisterone acetate/ethinylestradiol (FemHRT) for women with menopausal symptoms.

INTRODUCTION: The objective of this study was to assess the cost effectiveness of a continuous combined oral preparation of norethisterone (norethindrone) acetate and ethinylestradiol (NA/EE) [FemHRT] as both a first-line and second-line therapy for menopausal women. PERSPECTIVE: Third-party payer. METHODS: The cost effectiveness of NA/EE was assessed as both a first- and second-line therapy in comparison with conjugated equine oestrogen 0.625mg and medroxyprogesterone acetate 2.5mg (CEE/MPA) and no therapy. Analysis was conducted within a Markov model with states relating to the presence and absence of vaginal bleeding, menopausal symptoms and hip fracture. Analysis forecasted life expectancy, QALYs and lifetime costs for a 50-year-old menopausal woman. Compliance was modelled related to menopausal symptoms and vaginal bleeding. For the base-case analysis, it was assumed that compliant women would take therapy for up to 5 years. Sensitivity analysis assumed therapy was taken only for 1 year. RESULTS: Compared with both CEE/MPA and no therapy, NA/EE led to an increase in both costs and QALYs, both as a first- and second-line therapy. For first-line therapy, the incremental cost per QALY gained for NA/EE was $2200 Canadian dollars ($Can; 1999 values) [compared with no therapy] and was $Can20 300 (compared with CEE/MPA). For second-line therapy, the incremental cost per QALY gained for NA/EE was $Can900 (compared with no therapy) and was $Can16 400 (compared with CEE/MPA). Results were robust to most sensitivity analyses. CONCLUSIONS: NA/EE is a cost-effective therapy for women with menopausal symptoms both as a first-line and second-line therapy.

A cost-benefit analysis of four hormonal contraceptive methods.

This paper presents the results of a cost-benefit analysis conducted for pregnancy prevention treatment with four hormonal methods of contraception using a managed-care viewpoint. The therapies analyzed are medroxy-progesterone acetate injection (Depo-Provera), levonorgestrel subdermal implants (Norplant), progestogenonly oral tablets (Nor-QD), and combination progestogen/estrogen oral tablets (Ortho-Novum 7/7/7). Cost and benefits associated with the use of therapies are identified and analyzed based on the cost per patient-day of effective pregnancy prevention. The analysis demonstrates that all four methods have a positive net benefit, with Depo-Provera having the highest net benefit. This information can provide decision makers within a pharmacy and therapeutics committee of a managed-care organization the framework on which to base formulary decisions.

Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: a double-blind randomized study. European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group.

PURPOSE: In the present phase III study, the specific effect of estrogenic recruitment was assessed by comparing two groups of patients with advanced breast cancer receiving either ethinylestradiol (EE2) or placebo (PL) before chemotherapy (CT). PATIENTS AND METHODS: The therapeutic regimen consisted of (1) estrogen suppression by aminoglutethimide (AGL) 1 g/d plus hydrocortisone (HC) 40 mg/d, with surgical castration performed on premenopausal patients; (2) fluorouracil (5-FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide (CPA) 500 mg/m2 (FAC) intravenously (IV) every 3 weeks; (3) following randomization, patients were double-blinded to receive either PL or EE2 50 micrograms exactly 24 hours before receiving FAC. All patients had advanced breast cancer presumably sensitive to endocrine therapy (estrogen receptor-positive [ER+] and/or progesterone receptor-positive [PgR+] status) with measurable lesions; none had received prior systemic antineoplastic therapy for metastatic disease; prior adjuvant hormonal therapy (HT) or CT (without anthracyclines) was allowed if interval since completion was longer than 1 year. RESULTS: Among 154 patients treated according to the protocol, tolerance, response rates, time to progression, and median survival duration were identical in the PL and EE2 groups. Only performance status, dominant metastatic site, and menopausal status seemed to influence response (overall response, 64%), with the highest levels of partial remission (PR) and complete remission (CR) being achieved in premenopausal women (CR plus PR, 26% plus 55%) and in those with dominant soft tissue lesions (CR plus PR, 45% plus 28%). CONCLUSION: We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice so that this approach remains experimental. The results achieved by combining (near) complete estrogenic suppression and cyclical FAC chemotherapy are not significantly different from those to be expected with the more conventional use of HT followed by CT in presumably hormone-responsive (ER+) patients.

Comparative assessment of two low-dose oral contraceptives, Lo-Femenal and Lo-Estrin, in Mexican women.

This trial was designed to determine the differences in effectiveness, clinical acceptability, and one-year discontinuation rates of two low-dose oral contraceptives: Lo-Estrin (norethindrone acetate 1.5 mg plus ethinyl estradiol 0.030 mg) and Lo-Femenal (norgestrel 0.30 mg plus ethinyl estradiol 0.030 mg) in 148 Mexican women. In addition, the effects of both oral contraceptive preparations on blood lipids were prospectively evaluated in a subgroup of 41 women. The results indicated that there were no differences in pregnancy rates, discontinuation or clinical acceptability between the two groups. The lipid changes observed were minimal for the Lo-Femenal subgroup and somewhat greater for the Lo-Estrin group, mainly an increase in serum triglycerides. These changes were interpreted as estrogen induced effects of norethindrone-containing oral contraceptives. Overall, the data indicate that both Lo-Femenal and Lo-Estrin are effective and safe combined oral contraceptives.

Therapeutic alternatives for the hirsute woman.

A retrospective analysis of 21 hirsute women seen at a gynaecological endocrine clinic revealed a high incidence of infertility, menstrual irregularities and abnormal androgen profile. Polycystic ovarian syndrome (PCOS) was the underlying abnormality in the majority of cases. Cyproterone acetate (CPA) with ethinyl oestradiol in a reverse sequential regime was more effective and better tolerated but much more expensive than the combination of spironolactone and the oral contraceptive pill (OCP).

An assessment of (1) cyproterone acetate and (2) ethinyl oestradiol and lynoestrenol (Minilyn) in the treatment of idiopathic hirsutism.

The administration of cyproterone acetate can be effective in the treatment of 'idiopathic' hirsutism. In 5 similarly affected patients treated with ethinyloestradiol and lynoestrenol (Minilyn) the rate of hair growth was reduced in only two, even though the serum total testosterone was reduced in each instance.

Significance of quantitative assessment of estrogen receptors for endocrine therapy in advanced breast cancer.

The predictive significance of quantitative assessment of estrogen receptors in tumor tissue was analyzed in women with advanced breast carcinoma. Receptor concentration was measured by the 3H-estradiol binding capacity of the cytosol fraction of biopsies taken before initiation of the treatment. The E. O. R. T. C. criteria for the assessment of the patients' response were used. In a total of 34 assessments, 25 biopsies contained receptors; the remaining ones were negative. Objective remission to various endocrine therapies was recorded in only eight of the receptor-positive patients. Responses occurred along the whole scale of receptor concentrations with an apparent crowding in the region of the higher values. Linear logistic regression analysis revealed that among 12 variables of known prognostic value, receptor concentration was the most significant in relation to therapeutic response. Other significant variables were bone involvement and age. Computations yielded formulas that are presented in graph form and provide an estimate of the probability of a given patient to respond to endocrine treatments. On the other hand, the results suggest that all patients are possibly hormone dependent, although to variable degrees. The latter concept has very definite therapeutic implications.