Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception

BACKGROUND: Combined testosterone and progestogen preparations are a promising approach to male hormonal contraception. We investigated the effect of s.c. etonogestrel with depot testosterone on spermatogenesis in normal men over a period of 48 weeks. METHODS: Fifteen healthy men received three s.c. 68 mg etonogestrel implants. Testosterone pellets (400 mg) were administered at 12 weekly intervals. RESULTS: Nine men completed 48 weeks of treatment. Four subjects chose to discontinue after 6 months, one man withdrew from the study early for personal reasons and one was withdrawn due to illness. Sperm concentrations of <1 x 10(6)/ml were achieved in all men by 16 weeks of treatment. All men became azoospermic, although the time to achieve this varied from 8 to 28 weeks. Azoospermia was maintained in eight of the nine men treated for 48 weeks, one subject showing partial recovery from 40 weeks. Testosterone levels remained in the physiological range throughout. Treatment did not result in weight gain, change in body composition or decline in high-density lipoprotein cholesterol concentrations. CONCLUSIONS: The combination of three etonogestrel implants with depot testosterone results in rapid and consistent suppression of spermatogenesis. This can be maintained for up to 1 year and may therefore be a suitable approach for a long-acting male hormonal contraceptive.     

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men

BACKGROUND: Effective hormonal male contraception requires a high prevalence of spermatogenic suppression, which has proved particularly difficult in Caucasian populations. We have investigated the combination of oral desogestrel with depot testosterone in Caucasian and Chinese men. METHOD: Thirty men in Edinburgh and 36 men in Shanghai received 150 or 300 microg desogestrel p.o. daily for 24 weeks with 400 mg testosterone pellets s.c. on day 1 and at 12 weeks. RESULTS: Eight men withdrew before completing 24 weeks treatment. Testosterone concentrations remained within the normal range. Spermatogenesis was profoundly suppressed in all men. Azoospermia was achieved by a higher proportion of men in the 300 microg desogestrel group: 28/28 men versus 22/31 men (P < 0.05). All Caucasian men in the 150 microg group achieved sperm concentrations of < 1 x 10(6)/ml whereas three men in the Shanghai group maintained sperm concentrations of > 3 x 10(6)/ml. Fifteen men continued on this regimen for a subsequent 24 weeks: all remained azoospermic for the duration of treatment. High-density lipoprotein cholesterol fell by 15% in Caucasian men, but was unchanged in the Chinese men; both groups showed some weight gain. CONCLUSION: This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.     

Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men

Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.     

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.     

High-dose atorvastatin causes regression of endometriotic implants: a rat model

BACKGROUND: This prospective randomized-controlled animal study was designed to determine the effects of atorvastatin on experimentally induced endometriosis in a rat model. METHODS: Thirty-seven Wistar-Albino rats in which endometriotic implants were induced were randomly divided into four groups. Group I (Low-dose atorvastatin group, eight rats) were given 0.5 mg kg(-1) day(-1) oral atorvastatin. Group II (High-dose atorvastatin group, 10 rats) were given 2.5 mg kg(-1) day(-1) oral atorvastatin. Group III were given a single dose of 1 mg kg(-1) s.c. leuprolide acetate (GnRH agonist group, nine rats). Group IV were given no medication and served as controls (10 rats). All rats received the treatment for 21 days and were then euthanized to assess the implants' size, vascular endothelial growth factor (VEGF) level in peritoneal fluid and histological score. RESULTS: At the end of the treatment, the mean areas of implants were smaller and VEGF levels in peritoneal fluid were lower in Groups II and III than those in Group I and the control group (all P < 0.05). The mean areas of implants decreased from 41.2 +/- 13.9 to 22.7 +/- 13.9 mm(2) after medication in Group II and decreased from 41.2 +/- 18.1 to 13.1 +/- 13.8 mm(2) in Group III (both P < 0.05), whereas in Group I, the mean area increased from 43.0 +/- 12.7 to 50.5 +/- 13.9 mm(2) (P < 0.05). CONCLUSIONS: High-dose atorvastatin caused a significant regression of endometriotic implants.     

An investigation of the effectiveness of testosterone implants in combination with the prolactin inhibitor quinagolide in the suppression of spermatogenesis in men

BACKGROUND: Administration of testosterone inhibits gonadotrophin secretion and spermatogenesis in men but the degree of response is highly variable. This treatment also stimulates prolactin, itself a progonadal hormone in animals. This study investigated whether concomitant suppression of prolactin (PRL) with the non-ergot, dopamine receptor agonist quinagolide (Q), would enhance the efficacy of testosterone in its inhibition of spermatogenesis in healthy eugonadal men. METHODS: A total of 46 men were randomized to three treatment groups: Group 1, T1200: 1200 mg testosterone implant plus daily oral placebo; Group 2, T1200 + Q: 1200 mg testosterone plus oral Q 75 microg/day; Group 3, T800 + Q: testosterone 800 mg plus oral Q 75 microg/day. After an initial pre-treatment period of 4 weeks, subjects were treated for 24 weeks followed by an 8-week recovery period. RESULTS: The total numbers of subjects that achieved severe oligospermia (< or =10(6)/ml including azoospermia) from weeks 8-16 were 11/13 (85%), 11/12 (92%), 8/13 (61.5%) in the three groups respectively. CONCLUSIONS: The results show that inhibition of PRL does not to confer additional efficacy in spermatogenic suppression in men. However, Q did not totally block PRL secretion in the subjects, possibly because testosterone replacement itself stimulated PRL by a direct action on the lactotroph, thus the effectiveness of dual inhibition of gonadotrophin and PRL could not be fully investigated.     

Investigation of suppression of the hypothalamic-pituitary-gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer

BACKGROUND: Does suppression of the hypothalamic-pituitary-gonadal (HPG) axis restore spermatogenesis in men rendered azoospermic following treatment of childhood cancer? METHODS: Seven men with azoospermia secondary to treatment for childhood cancer, median age (range), 22.2 (18-25.3) years, aged 10.4 (4.4-13.3) years at original diagnosis, participated. Each subject underwent semen analysis and testicular biopsy, followed by treatment with medroxyprogesterone acetate (MPA), 300 mg i.m. repeated after 12 weeks, with 800 mg testosterone pellets s.c. on day 1 to suppress the HPG axis. Hormone and semen analysis was performed every 6 weeks for 48 weeks. A second testicular biopsy was performed at week 48. RESULTS: Before HPG axis suppression, mean +/- SEM plasma LH was 9.0 +/- 1.8 U/l, testosterone 17.9 +/- 1.5 nmol/l and FSH 22.4 +/- 4.4 U/l. Median (range) venous plasma and seminal plasma inhibin B levels were 10.0 (7.8-35) and 11.2 (7.8-770) ng/l respectively. During HPG suppression, FSH and LH levels were undetectable for > or =12 weeks followed by a gradual return to pretreatment concentrations by 48 weeks. All men remained azoospermic at study completion and complete absence of germ cells on biopsies was demonstrated by immunocytochemistry for all specimens pre- and post-HPG axis suppression. CONCLUSIONS: HPG axis suppression with MPA-testosterone for > or =12 weeks did not restore spermatogenesis in azoospermic men treated with gonadotoxic radiotherapy and chemotherapy for childhood cancer.     

Cytomorphometric analysis of vaginal cells during normal cycle, under oral contraceptive therapy or in-vitro fertilization stimulation protocol

A cytomorphometric analysis of superficial vaginal cells inwomen in three groups of different types of hormonal concentrationwas made. There were 15 women in each group. Group I was studiedduring a natural cycle, group II under oral contraceptive therapyand group III during an in-vitro fertilization (IVF) stimulationprotocol. Morphometric parameters were measured on an imageanalyser. The area, perimeter and several form factors weremeasured separately for nuclei and cytoplasm. The nucleus:cytoplasmicratio was also determined. The cytoplasmic area was significantlyreduced in group II and was associated with a statisticallysignificant reduction of the nuclear area. The nucleus:cytoplasmicratio appeared significantly increased in group II and reducedin group III. Low oestradiol impregnation obtained with an oralminidosed contraceptive interfered with vaginal cell maturation.High oestradiol concentrations obtained during IVF protocolsinduced marked nuclear pycnosis but did not induce supra-physiologicalcell enlargement. Maximal cell size is genetically regulatedaccording to Driesch's law of volume invariance and hormonalover-stimulation has no effect on cell size. The nucleus:cytoplasmicratio appears to be a powerful parameter reflecting the oppositeeffects of hormones on cell compartments.     

Oestradiol enhances testosterone-induced suppression of human spermatogenesis

The aim of this study was to determine for the first time in humans, the efficacy of adding a low dose oestradiol to a suboptimally suppressive testosterone dose in a depot hormonal regimen to suppress spermatogenesis in healthy eugonadal men. Twenty-six healthy men were randomized into groups that were treated by a single subdermal implantation of either 600 mg testosterone alone (T; n = 11) or together with 10 mg (TE10, n = 7) or 20 mg (TE20, n = 8) oestradiol. Administration of oestradiol produced a dose-dependent increase in peak plasma oestradiol at 1 month and prolonged suppression of plasma LH and FSH leading to significantly enhanced suppression of sperm output. Despite the augmented spermatogenic suppression, there was no significant difference in the proportions achieving azoospermia (6/26, 23%) or severe oligozoospermia (<1 or <3 x 10(6) spermatozoa per ml, 7/26, 27%) and overall these proportions were inadequate to provide reliable contraception according to the standards identified in World Health Organization male contraceptive efficacy studies. Total and free testosterone remained within the eugonadal reference range for young men throughout the study. While the lower oestradiol dosage had minimal spermatogenic suppression effects, the higher dose produced dose-limiting adverse effects of androgen deficiency and/or oestrogen excess between the fourth and sixth month of the study. This appeared to be due to the unexpectedly prolonged, low concentration of oestradiol release from the oestradiol implants. There were no significant treatment-related changes in body composition, lipids, prostate-specific antigen, haematological or biochemical variables. Thus oestradiol has a low therapeutic window and dose-limiting side-effects at dosages that fail to achieve the uniform azoospermia required of an effective male hormonal contraceptive regimen.     

The effect of various doses of mifepristone on endometrial leukaemia inhibitory factor expression in the midluteal phase--an immunohistochemical study

Leukaemia inhibitory factor (LIF) is a cytokine which plays an obligatory role in mouse blastocyst implantation. In human endometrium, LIF expression is significantly increased in the mid-luteal phase indicating that LIF may also play an important role in the human. We have previously shown that a single dose of 200 mg of mifepristone immediately post-ovulation is an effective contraceptive method, probably due to inhibition of endometrial development and function. The purpose of this study was to investigate the effect of various doses of mifepristone on endometrial LIF expression. A total of 22 fertile, regularly-menstruating women were studied during control and treatment cycles. The subjects were divided into four groups: group I received a single dose of 200 mg of mifepristone on cycle day LH + 2 (n = 7). The subjects in groups II and III were treated with either 5 mg (n = 5) or 2.5 mg (n = 5) once a week for 2 months. Group IV subjects received 0.5 mg per day (n = 5) of mifepristone for 3 months. LIF was measured immunohistochemically in endometrial tissue specimens taken on the corresponding day (cycle day LH + 6 to LH + 8) in hormonally- characterized control and treatment cycles. LIF immunostaining was observed in all controls and located to the cytoplasm of the luminal and glandular epithelial cells and stromal cells. In the treatment cycles the staining of luminal epithelium and stroma was similar to controls, while the glandular staining was reduced in all treatment groups. This study reveals that early luteal phase treatment as well as intermittent or daily low dose treatment with mifepristone reduces endometrial glandular LIF expression at the expected time of implantation. The results further support the contraceptive potential of mifepristone in low doses.      

Rates of suppression and recovery of human sperm output in testosterone-based hormonal contraceptive regimens

BACKGROUND: Practical hormonal male contraceptive regimens are likely to have delayed onset and offset of reliable contraception dictated by the length of the spermatogenic cycle and clearance rate of pre-formed sperm from the ductular system. While delayed onset of contraceptive efficacy is an accepted feature of vasectomy, reliable time estimates for a hormonal male contraceptive of time to onset and offset of reliable contraception and of resumption of normal male fertility are required. METHODS AND RESULTS: We utilized the sperm output data from three male contraceptive efficacy studies to define quantitative estimates of suppression and recovery rates from an androgen alone (testosterone enanthate) and an androgen/progestin (testosterone/depot medroxyprogesterone acetate) study. Using nearly 14,000 semen samples from World Health Organization (WHO) studies #85921 and #89903 with identical protocols, the rate of suppression of sperm output was best modelled as a two-parameter, single exponential decay function with effective half-time to suppression of 5.5 weeks and times of 6.8 weeks to 10 x 10(6)/ml, 8.7 weeks to 5 x 10(6)/ml, 10.0 weeks to 3 x 10(6)/ml and 13.0 weeks to 1 x 10(6)/ml. The rate of recovery using absolute sperm concentration was best modelled as a three-parameter, sigmoidal curve with effective time to reach half of the recovery plateau of 10.5 weeks and times of 9.0 weeks to 3 x 10(6)/ml, 9.9 weeks to 5 x 10(6)/ml, 11.5 weeks to 10 x 10(6)/ml, and 13.6 weeks to 20 x 10(6)/ml. Using relative sperm output, defined as a percentage of the participants' own baseline, recovery approached an asymptotic plateau of approximately 85% of geometric mean pre-treatment sperm concentration. In the combination androgen/progestin study, suppression rate was significantly faster (effective time to reach half maximal suppression of 3.0 weeks) and recovery significantly slower (effective time to reach half of recovery plateau of 14.7 weeks) and less complete (asymptotic recovery plateau of 43% of baseline) than in the androgen-alone WHO studies. CONCLUSION: These findings therefore provide large sample estimates of the suppression and recovery rates from an androgen-alone hormonal male contraceptive regimen as a basis for comparison with other second-generation combination androgen/progestin regimens that are the most promising approach to developing practical male hormonal regimens.     

Effect of ovulation induction on uterine blood flow and oestradiol and progesterone concentrations in early pregnancy

To determine if oestradiol and progesterone concentrations arerelated to uterine blood flow in early pregnancy, we measuredthese hormones at the time of vaginal Doppler ultrasound beforeand after the beginning of intervillous circulation in spontaneouspregnancy (group I), after clomiphene citrate administration(group II), and after clomiphene citrate plus human menopausalgonadotrophin (HMG) administration (group III). Despite largeincreases of oestradiol concentration in groups II (60%) andIII (300%) and of progesterone in groups II (100%) and III (300%),compared with group I, increases in blood flow were modest duringthe first 9 weeks of gestation. Uterine artery flow volume increasedby 20% in group II and 33% in group III (P 0.02); average velocityincreased by 37% in group III (P < 0.003) compared with groupsI and II; vessel diameter increased by 15% in groups II (P <0.025) and III (P < 0.001) compared with group I; and theuterine artery resistance index decreased by 3 to 5% in groupHI (P = 0.004) compared with groups I and II. Serum oestradioland progesterone concentrations were unrelated to the uterineartery resistance index or volume by an analysis of covariance.We conclude that uterine artery blood flow is significantlyincreased during early pregnancyfollowing HMG administration,and that the increase is unrelated to increases in oestradioland progesterone concentrations.     

High efficacy of photodynamic therapy on rat endometrium after systemic administration of benzoporphyrin derivative monoacid ring A

BACKGROUND: The aim of this study was to evaluate the effect of the benzoporphyrin derivative monoacid ring A (verteporfin)-mediated photodynamic therapy (PDT) on rat endometrium and to determine the optimal drug concentration for endometrial ablation. METHODS: Five minutes after i.v. injection of different concentrations of verteporfin into 24 female Sprague-Dawley rats, 630 nm light treatment was delivered for 500 s (120 J/cm2) to the left horn of the uterus. The 24 rats were divided into six groups according to the drug dose injected, four rats per group: group I (2 mg/kg), group II (1 mg/kg), and groups III, IV, V and VI with 0.5, 0.25, 0.125 and 0.0625 mg/kg respectively. Four days later, the rat uteri were analysed by light microscopy. RESULTS: Endometrial destruction was seen in all six groups, with the most significant result in group I (P<0.008). Conservation of the myometrium was most significant in groups III, IV, V and VI. Acute inflammatory cells in the stromal endometrium were recorded mainly in groups I and II. However, the drug dosage that was most significant in destroying the glands with conservation of the myometrium and not causing severe inflammation was between 0.5 and 0.125 mg/kg. CONCLUSIONS: Verteporfin was effective in endometrial ablation in all our animal groups, and the dose range of 0.5-0.125 mg/kg appeared to be adequate. This observation will have to be scaled for clinical application.     

Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure

BACKGROUND: Gonadal failure secondary to alkylating agents may be related to ovulatory status. The objective of this investigation was to evaluate whether anovulation protected ovarian follicles during treatment with cyclophosphamide. METHODS: Four groups (n = 20 mature female Sprague-Dawley rats per group) were studied: control (group I), 5 mg/kg/day cyclophosphamide only (group II), 5 mg/kg/day cyclophosphamide and the combination of 50 micro g ethinyl estradiol/2 mg norgestrel (group III) and 5 mg/kg/day cyclophosphamide and 2.5 micro g leuprolide acetate daily (group IV). Animals were sacrificed after 4 weeks of treatment. Follicles were classified as medium (300-450 micro m) and large (>450 micro m) per section of ovary. RESULTS: Group II developed a significantly greater number of medium and large follicles [15.1 +/- 6.1 and 4.9 +/- 1.9 (mean +/- SD), respectively] compared with group I [7.1 +/- 2.1 and 1.0 +/- 0.7 (mean +/- SD), respectively] (P 相似文献   

The origin of serum progesterone during the follicular phase of menotropin-stimulated cycles

The study was designed to investigate the source of progesterone secretion during pituitary suppression and ovarian stimulation. It involved 416 women undergoing in-vitro fertilization (IVF) who were treated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group I), 139 women undergoing ovulation induction with HMG only (group II) and nine women who were diagnosed previously as late-onset adrenal hyperplasia and treated continuously with dexamethasone, in addition to ovulation induction (group III). During HMG treatment, serum oestradiol and progesterone were measured every 1-2 days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before human chorionic gonadotrophin (HCG) administration, the patients were prospectively randomized to treatment with dexamethasone or not and the hormones concentrations were measured again 12 h later. Mean age and pretreatment serum concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not significantly different in the patients with and without progesterone elevation. Pituitary down-regulation did not reduce the incidence of progesterone elevation (13.9 and 12.2% in groups I and II respectively), while in group III, progesterone concentrations did not increase. After dexamethasone administration a significant decrease in serum progesterone concentration was demonstrated (mean +/- SD, -2.1 +/- 1.4 and -1.6 +/- 1.2 in groups I and II respectively, while in the untreated patients it increased (+1.9 +/- 1.9 and +4.2 +/- 4.8). The increase in serum progesterone concentrations was not accompanied by an increase in cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone administration the concentrations of cortisol, 11- deoxycortisol and LH significantly decreased. Progesterone concentration was positively correlated with both oestradiol concentration (r = 0.290; P < 0.05) and the number of oocytes retrieved (r = 0.207; P < 0.05). We conclude that at least a part of serum follicular-phase progesterone appears to be of adrenal origin. High oestrogen concentrations (or other ovarian factors) may cause changes in the hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of the complex 'cross-talk' between the hypothalamic- pituitary-ovarian and the hypothalamic-pituitary-adrenal axes.      

Anabolic steroids alter the haemodynamic effects of endurance training and deconditioning in rats

The haemodynamic effects of endurance training with or without anabolic steroid treatment (nandrolone decanoate, 5.0 mg kg-1 week-1) were studied before and after a six-week sedentary period in anaesthetized, open-chest rats during isoproterenol and CaCl2 loads. In comparison to the control group (CG I, n = 13) endurance training (TG I, n = 10) increased the resting stroke index significantly, end-diastolic pressure and during CaCl2 infusion the end-diastolic and end-systolic volumes. Peripheral resistance decreased in TG I during both inotropic loads but increased in CG I (P less than 0.01 between the groups). After combined endurance training and anabolic steroid treatment (TSG I, n = 16) the haemodynamic state was similar to that in CG I except peripheral resistance which was even higher than in CG I. The heart weight to body weight ratio was significantly greater both in TG I and TSG I than in CG I. After a six-week deconditioning period the haemodynamic values were essentially similar in endurance trained (TG II, n = 10) and in control rats (CG II, n = 12). After the sedentary period, in the simultaneously trained and anabolic steroid-treated group (TSG II, n = 13) stroke index and end-diastolic volume decreased more during isoproterenol load when compared with TG II or CG II (P less than 0.05 between the groups). Peripheral resistance was higher in the TSG II than in the two other groups. In conclusion, the enhanced pumping performance of the heart by increased left ventricular diastolic filling after endurance training is attenuated by simultaneous anabolic steroid treatment which further increases the peripheral resistance. Detraining reversed the main training effects in six weeks and simultaneous anabolic steroid treatment led to a decreased left ventricular filling and to elevated peripheral resistance after the sedentary period.     

Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome

BACKGROUND: The aim of this study was to evaluate the effects of metformin and acarbose on insulin resistance, hormone profiles and ovulation rates in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). METHODS: Thirty clomiphene citrate-resistant patients were selected randomly and divided into two groups. Group I was treated with 100 mg/day clomiphene citrate and 300 mg/day acarbose 100 mg/day orally, for 3 months. Group II was treated with clomiphene citrate 100 mg/day and metformin 1700 mg/day orally, for 3 months. Serum fasting insulin and glucose, FSH, LH, estradiol, progesterone, prolactin and total testosterone levels plus body mass index (BMI) were measured before and after treatment. Follicle growth was followed by transvaginal ultrasonography. RESULTS: LH:FSH ratio and total testosterone concentrations decreased (P<0.05) and ovulation rates increased in both groups. Reduction in weight and BMI was only significant in the acarbose group. CONCLUSIONS: Both treatment modalities were effective in the treatment of insulin resistance and improving ovulation rates. Increase in the number of eumenorrhoeic and normoinsulinaemic cases and decrease in the number of insulin-resistant cases were significant in both groups (P<0.05). Ovulation rate was greater in the metformin group in the second month of therapy (P<0.05). Acarbose was found to be a safe and effective agent that could be used in cases with clomiphene-resistant PCOS.     

Low dose of cyproterone acetate and testosterone enanthate for contraception in men

After a control phase, 10 normal men received cyproterone acetate (CPA) at a dose of 25 mg/day (CPA-25; n=5) or 12.5 mg/day (CPA-12.5; n=5) plus testosterone enanthate (TE) 100 mg/week, for 16 weeks. Throughout the study sperm counts were performed every 2 weeks, and luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, biochemical and haematological tests were performed every 4 weeks. All five men in group CPA-25 and three men in group CPA-12.5 achieved azoospermia. One man in group CPA-25 was azoospermic by week 12 of hormone administration, but had a sperm count of 0.1 x 10(6)/ml at week 16. Time to azoospermia was 9.0+/-1.3 and 8.7+/-0.7 weeks in groups CPA- 25 and CPA-12.5 respectively. Gonadotrophins were decreased by week 4 of hormone administration, remained around the minimum detectability of the assay for the duration of hormone administration and returned to baseline after stopping hormone administration. Testosterone values did not change. No change in any biochemical parameters was found. Haematological parameters were decreased at week 16 of hormone administration and returned to baseline after stopping hormone administration. In conclusion, these results suggest that an hormonal regimen consisting of testosterone plus a progestin with anti- androgenic properties holds promise as an effective, safe and reversible male contraceptive.      

Ovarian function with the contraceptive vaginal ring or an oral contraceptive: a randomized study

BACKGROUND: The effects on ovarian function of the combined contraceptive vaginal ring NuvaRing and a combined oral contraceptive (COC) were compared. METHODS: This randomized, open-label study was performed in 40 healthy female volunteers, who were randomized by a computer-generated list after stratification for the ovulation day in a pretreatment cycle. They received two cycles of NuvaRing (21 subjects) or a COC (30 microg ethinylestradiol and 150 microg levonorgestrel, 19 subjects). NuvaRing was started on cycle day 5, COC on cycle day 1. Follicular diameter, endometrial thickness and FSH, LH, 17beta-estradiol (E2) and progesterone concentrations were determined. RESULTS: The median maximum follicular diameter (maxFD) was < or =11 mm during treatment. In the first treatment cycle the maxFD was lower in the COC than in the NuvaRing group, due to the different starting procedures. MaxFD were not different in the second treatment cycle. In both groups, E2 and progesterone levels remained low during treatment. Ovulations did not occur. CONCLUSIONS: In both groups, ovarian activity was adequately suppressed. Due to the different starting procedures, lower ovarian activity was observed in the COC group in the first treatment cycle. In the second cycle, ovarian suppression was comparable with NuvaRing and COC treatment.     

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.