绝经过渡期妇女血清抑制素水平的研究

目的　分析绝经过渡期妇女血清抑制素A(Inh A)、抑制素B(Inh B)水平的变化及其与其他生殖激素水平变化的时间关系。方法　测定 10例正常育龄妇女月经周期各期血清Inh A、Inh B水平 ;测定 40例绝经过渡期妇女月经周期第 3天的血清Inh B、促卵泡激素 (FSH)、促黄体生成素(LH)、雌二醇 (E2 )水平 ,经前 5～ 9d(经前期 )血清Inh A、孕酮 (P)水平 ;测定 10例绝经后妇女的血清Inh A、Inh B、FSH、E2 水平。分析各项激素水平变化之间的时间关系。结果　育龄妇女月经周期中Inh A、Inh B水平的变化曲线各不相同。绝经过渡期妇女中 ,黄体功能正常者占 48% ,经前期Inh A水平低于育龄妇女 ,分别为 ( 2 4 7± 13 0 )及 ( 42 9± 12 1)ng/L ,两者比较 ,差异有显著性 (P =0 0 17) ,Inh B水平改变差异无显著性 (P >0 0 5 ) ;黄体功能不足与无排卵者的Inh A水平进一步显著下降 ,分别为 ( 12 4± 10 2 )及 ( 5 3± 3 8)ng/L(P分别为 0 0 3 3及 <0 0 0 0 1) ,绝经后妇女则皆未检出。与育龄妇女比较 ,月经周期第 3天Inh B水平的下降仅在无排卵与绝经后妇女差异有极显著性 (P =0 0 0 1)。月经周期第 3天 ,FSH≥ 10IU/L者Inh B水平显著低于FSH <10IU/L者 ,分别为 ( 16 2± 4 0 )及 ( 62 0±43 8)ng/L(P <0 0 0     

绝经后阴道出血妇女性激素水平与子宫内膜病变关系的研究

目的　探讨绝经后阴道出血的妇女性激素变化及与子宫内膜病变的关系。方法　采用酶免疫法对 4 6例绝经后阴道出血的患者性激素水平测定。结果　绝经后阴道出血妇女血清E2 水平远高于正常绝经后妇女血清E2 值 ,两者存在显著性差异 (P <0 0 1 )。FSH、LH与正常绝经后妇女比较明显降低 (P <0 0 5 )。子宫内膜增生过长和子宫内膜癌的患者雌激素水平增高者分别占 71 4 %和 5 7 1 %。结论　绝经后阴道出血与雌激素水平增高有关     

卵巢功能早衰伴有持续性泌乳素释放

曾有报道,健康妇女卵巢切除后血浆泌乳素明显升高,PRL升高趋势与去势后FSH和LH升高相类似。几周后,由于雌激素生成减少,血浆PRL水平降低,绝经妇女比未绝经者更低。然而绝经后妇女使用HCG可诱发PRL释放2～3天。作者研究了5例闭经并在近期内(5～12月)有过早绝经症状的妇女和1例20岁原发性卵巢功能衰竭的患者,分别于调查初     

甘肃省绝经过渡期和绝经后期女性潮热症状发生率及其相关因素

目的:分析甘肃地区绝经过渡期和绝经后期妇女潮热症状的发生率,探讨潮热相关影响因素。方法:2016年7—10月按照多阶段整群随机抽样的方法对甘肃13个市/州54个区/县162个乡/镇40～55岁妇女进行横断面研究,采用问卷调查的方式进行潮热症状的相关信息收集,并分析其可能影响因素。结果:本研究获得有效问卷2 807份,其中绝经过渡期妇女1 393例、绝经后期妇女1 414例。存在潮热症状者1 758例(62.6%),其中轻度潮热880例(50.1%),中度潮热624例(35.5%),重度潮热254例(14.4%)。Logistic回归分析显示,年龄增加(OR=1.070,P=0.000)、高血压(OR=1.547,P=0.000)、痛经(OR=1.422,P=0.000)是潮热发生的危险因素。相较于正常体质量妇女,超重(OR=1.293,P=0.001)、肥胖(OR=2.056,P=0.000)妇女更易发生潮热。另外,回族妇女比汉族妇女更易发生潮热(OR=1.802,P=0.000),体力劳动者较脑力劳动者更易发生潮热(OR=1.392,P=0.013)。结论:甘肃地区62.6%的绝经过渡期和绝经后期女性受潮热问题困扰。年龄增加、BMI增高、高血压、痛经是潮热发生的危险因素,民族差异也与潮热的发生相关,体力劳动者比脑力劳动者更易发生潮热。     

年龄、绝经年限与骨代谢指标相关性研究

目的 :探讨妇女不同年龄段、绝经年限、初潮年龄的骨代谢指标的变化。方法 :随机选择年龄 2 0～ 75岁的妇女 2 10例 ,测定血清钙 (Ca)、磷 (P)、碱性磷酸酶 (ALP)、性激素 ,尿钙 /肌酐 (Ca/Cr)值。结果 :骨代谢指标与年龄、绝经年限、初潮年龄均呈正相关 ,40岁以上的妇女的骨代谢指标明显高于 40岁以下的妇女 (P <0 0 5 ) ;初潮年龄在 18岁以上的妇女骨代谢指标明显增高 (P <0 0 5 ) ;绝经后E2 水平较绝经前降低 (P <0 0 5 ) ,但不同绝经年限间差异无显著性 (P >0 0 5 ) ;绝经后骨代谢指标较绝经前增高 (P <0 0 5 ) ,尤其在绝经后 10年以上增高更明显。结论 :妇女在围绝经早期出现骨转换率增高 ,可能与雌激素下降有关 ,因此对围绝经早期妇女 ,尤其是初潮年龄晚者 ,应进行骨代谢指标测定 ,筛查并及时预防骨质疏松症     

绝经后妇女雌激素替代治疗：雌三醇的疗效及血浆促性腺激素水平变化的研究

为确定绝经后妇女应用雌三醇(E_3)作雌激素替代治疗(ERT)的效果及治疗期间血浆促性腺激素(FSH、LH)的改变进行下述研究。观察对象为245例无明确症状的绝经后妇女。分为治疗组168例和安慰剂组77例。已停经12月者为自然绝经,通过检测绝经后FSH、LH、E_2水平确定绝经,FSH≥30 IU/L,LH≥15 IU/L,E_2<92 pmol/L。既往无用激素替代疗法(HRT)史,放免法检测激素水平。E_3治疗2 mg/d或安慰剂8周。治疗开始时及治疗后2、4及8周进行临床评估。     

正常妊娠和妊娠高血压综合征妇女血清瘦素水平的动态检测

目的　动态检测正常妊娠、妊娠高血压综合征 (妊高征 )妇女血清瘦素水平的变化特点。方法　采用放射免疫法测定 40例正常非妊娠妇女 (对照组 )以及 5 0例正常妊娠和 14例妊高征妇女(观察组 )孕 16～ 2 0、2 4～ 2 8、3 2～ 3 6周及分娩前的血清瘦素水平及其新生儿的脐血瘦素水平 ,同时测量身高、体重、血压及胎盘重量。结果　 ( 1)随着孕周的增加 ,观察组妇女血清瘦素水平呈上升趋势 ,其中妊高征妇女血清瘦素水平为 ( 14 1± 2 2 )～ ( 2 5 4± 2 7) μg/L ,较正常妊娠妇女的 ( 13 4± 3 0 )～( 2 1 4± 3 7) μg/L明显上升 (P <0 0 1) ,并持续至妊娠结束 ,而正常妊娠妇女血清瘦素水平在孕 2 8～3 6周时上升明显 ,孕 2 8周前及孕 3 6周后上升缓慢。 ( 2 )体重、体重指数与血清瘦素水平的相关性分析结果显示 ,正常妊娠、对照组妇女均呈显著性正相关 (r =0 478～ 0 63 9,P <0 0 5或P <0 0 1) ,而妊高征妇女无显著相关性 (r=0 0 3 5～ 0 3 79,P >0 0 5 )。( 3 )收缩压、舒张压、平均动脉压与血清瘦素水平的相关性分析结果显示 ,正常妊娠、孕 2 0周前的妊高征及对照组妇女无显著相关性 (r=0 113～0 498,P >0 0 5 ) ,而妊高征妇女孕 2 0周后呈显著正相关 (r=0 63 9～ 0 85 2 ,P <0 0 5 )     

病理性高泌乳素血症抑制绝经妇女潮热

本文研究了溴隐亭(CB_(154))治疗前后病理性高PRL血症对2例绝经妇女促性腺激素(Gn)分泌及潮热的影响。例1,59岁,主诉左侧严重头痛4年。闭经35年无泌乳。CT扫描显示垂体大腺瘤有鞍上的扩张。血浆PRL水平766μg/l,LH7.4IU/1,FSH14.6IU/1。遂服CB~(154)7.5mg/日3周后头痛消失,第4周出现潮热。2月后复查CT肿瘤缩小。PRL下降至34.8μg/l。LH及FSH各上升至31.4及35.2IU/1。改服雌/孕激素(E/P)替代共22个月。潮热消失。PRL17.1μg/l。LH及FSH各为41.5及78.5IU/1。     

绝经后妇女激素替代疗法血浆中一氧化氮水

为估价绝经后妇女激素替代治疗(HRT)时血浆一氧化氮(NO)水平的影响进行一项随机双盲安慰剂一对照交叉试验研究。绝经后妇女共28例,子宫及双侧卵巢均已切除,年龄47～56岁,闭经1～5年,体重正常(体质指数≤25kg/m~2),闭经是由血清FSH>40mIU/ml和E_2<20pg/ml确诊,有类似生活方式与饮食习惯,研究期间要求不改变这些习惯。无潮热,以往无接受(HRT)史,无冠状动脉病、高血     

甘肃省绝经过渡期和绝经后期女性潮热症状发生率及其相关因素

目的：分析甘肃地区绝经过渡期和绝经后期妇女潮热症状的发生率，探讨潮热相关影响因素。方法：2016年7—10月按照多阶段整群随机抽样的方法对甘肃13个市/州54个区/县162个乡/镇40～55岁妇女进行横断面研究，采用问卷调查的方式进行潮热症状的相关信息收集，并分析其可能影响因素。结果：本研究获得有效问卷2 807份，其中绝经过渡期妇女1 393例、绝经后期妇女1 414例。存在潮热症状者1 758例（62.6%），其中轻度潮热880例（50.1%），中度潮热624例（35.5%），重度潮热254例（14.4%）。Logistic回归分析显示，年龄增加（OR=1.070，P=0.000）、高血压（OR=1.547，P=0.000）、痛经（OR=1.422，P=0.000）是潮热发生的危险因素。相较于正常体质量妇女，超重（OR=1.293，P=0.001）、肥胖（OR=2.056，P=0.000）妇女更易发生潮热。另外，回族妇女比汉族妇女更易发生潮热（OR=1.802，P=0.000），体力劳动者较脑力劳动者更易发生潮热（OR=1.392，P=0.013）。结论：甘肃地区62.6%的绝经过渡期和绝经后期女性受潮热问题困扰。年龄增加、BMI增高、高血压、痛经是潮热发生的危险因素，民族差异也与潮热的发生相关，体力劳动者比脑力劳动者更易发生潮热。     

Predictors of hot flushes in postmenopausal women who receive raloxifene therapy

OBJECTIVE: In a previous report, we described the results of a randomized, controlled trial that evaluated the potential of raloxifene to induce or exacerbate hot flushes. Here, we provide additional analyses that were undertaken to identify potential predictors of hot flushes and to assess the clinical usefulness of various therapeutic strategies for the reduction of hot flushes in postmenopausal women who receive raloxifene therapy. STUDY DESIGN: In this randomized, double-blind, placebo-controlled study, 487 unselected postmenopausal women were assigned randomly to receive treatment for 8 months with raloxifene, which was administered either at a dose of 60 mg/d every other day for 2 months followed by 60 mg/d (slow-dose escalation) or 60 mg/d throughout (raloxifene), or placebo. Data on the number, duration, intensity, and severity of hot flushes and awakenings because of night sweats were collected. Logistic regression models were used to examine the predictive value of various demographic and menopausal factors on the development or worsening of hot flushes. RESULTS: At baseline, 40.4% of all randomly assigned patients had hot flushes. The mean number of hot flushes (3-5 per week) was low. Fewer years postmenopause, surgical menopause, and previous estrogen or estrogen/progestin therapy were significant predictors of hot flushes at baseline but were not predictive of incident hot flushes during treatment with raloxifene. Of the women who received raloxifene therapy who had pre-existing hot flushes at baseline, 36% women had none at the end point. Early postmenopause and surgical menopause were significant predictors of a biologically relevant increase in hot flushes (>/=14 flushes/week). Early postmenopause, previous estrogen/progestin therapy, high body mass index, and greater duration of hot flushes at baseline were significant predictors of the need for symptomatic treatment. After 2 months of treatment, women in early postmenopause had significantly more hot flushes with raloxifene therapy than with slow-dose escalation ( P = .042), whereas there was no significant difference between raloxifene therapy and slow-dose escalation among women in later postmenopause. In the 50 patients who requested symptomatic treatment during the study, phytohormones or veralipride did not reduce the number of hot flushes markedly. CONCLUSION: A shorter time since menopause and surgical menopause are important predictors of hot flushes both before and during treatment with raloxifene. Previous estrogen/progestin therapy also increases the risk of hot flushes at baseline. For women in early postmenopause, slow-dose escalation of raloxifene therapy may be a suitable therapeutic strategy for the reduction of the risk of hot flushes.     

Effects of soy isoflavones on menopausal neurovegetative symptoms

AIM: Dietary soy supplementation may reduce the incidence of hot flushes in postmenopausal women due to the presence of phytoestrogens in soy foods. The aim of this study was to assess the effects of a 3-month administration of different doses of either oral or transdermal soy isoflavones on climacteric complaints in postmenopausal women. METHODS: Sixty postmenopausal women were assigned randomly to one of the following groups: groups A and B received 50 mg/day or 75 mg/day of oral isoflavones respectively, while groups C and D received 6 mg/day or 12 mg/day of transdermal isoflavones. A control group (group E) was composed of 15 patients that did not receive any treatment. Hot flushes, Kupper-man index and vaginal dryness at baseline and then after 5, 9 and 13 weeks were evaluated. RESULTS: The isoflavone treatment led to a progressive significant (p<0.01) reduction of the number of hot flushes in the groups A, B and D with a dose-related effect in group D. At week 13, the Kupperman index and hot flush score decreased significantly in all the treated groups, while vaginal dryness score was reduced only in group B. CONCLUSION: Our findings suggest that both oral and transdermal soy isoflavones are effective to attenuate slight to moderate menopausal neurovegetative symptoms with a dose-related effect.     

The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial

OBJECTIVE: To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer. DESIGN: Double-blind, randomised, placebo-controlled, multicentre pilot study. SETTING: Hospital outpatient clinic. SAMPLE: Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer. METHODS: Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months. MAIN OUTCOME MEASURES: Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins. RESULTS: Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months. CONCLUSIONS: Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.     

A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in postmenopausal women.

OBJECTIVE: To compare the effects of electro-acupuncture with oral estradiol and superficial needle insertion on hot flushes in postmenopausal women. MATERIAL AND METHODS: Forty-five postmenopausal women with vasomotor symptoms were randomized to electro-acupuncture, superficial needle insertion or oral estradiol treatment during 12 weeks, with 6 months' follow-up. The number and severity of flushes were registered daily and the Kupperman index and a general estimate of climacteric symptoms were completed before, during and after therapy. RESULTS: In the electro-acupuncture group, the mean number of flushes/24 h decreased from 7.3 to 3.5 (ANOVA, p < 0.001). Eleven of the 15 women had at least a 50% decrease in number of flushes (with a mean decrease of 82%). Superficial needle insertion decreased the number of flushes/24 h from 8.1 to 3.8 (p < 0.001). In seven out of 13 women, the number of flushes decreased by at least 50% (mean decrease 83%). In the estrogen group, the number of flushes decreased from 8.4 to 0.8 (p < 0.001). The decrease in number of flushes persisted during the 24-week follow-up period in all treatment groups. The Kupperman index and the general climacteric symptom score decreased, and remained unchanged 24 weeks after treatment in all groups (p < 0.001). Electro-acupuncture decreased the number of flushes/24 h significantly over time, but not to the same extent as the estrogen treatment. No significant difference in effect was found between electro-acupuncture and the superficial needle insertion. CONCLUSION: We suggest that acupuncture is a viable alternative treatment of vasomotor symptoms in postmenopausal women and cannot recommend superficial needle insertion as an inactive control treatment.     

Dietary soy supplementation and phytoestrogen levels.

OBJECTIVE: To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. METHODS: Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. RESULTS: Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. CONCLUSION: Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.     

Menopause alters the metabolism of serum serotonin precursors and their correlation with gonadotropins and estradiol.

OBJECTIVE: Tryptophan, the serotonin (5-HT) precursor, is circulating in blood in both free (FT) and protein-bound forms. The free form crosses the hematoencephalic barrier and is converted into 5-HT. During the fertile years, tryptophan levels are negatively correlated to gonadotropin concentrations. The present study aims to evaluate the correlation between circulating tryptophan, gonadotropin and estradiol (E2) levels postmenopause. METHODS: Serum levels of total tryptophan (TT, free + protein-bound) and FT, and plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), and E2 were determined in 15 postmenopausal women and 15 cycling women during follicular (days 7-10), periovulatory (days 13-16) and luteal (days 21-24) phases of the menstrual cycle. Data were analyzed by ANOVA, linear correlation coefficients and hierarchical cluster analysis of variables. RESULTS: TT, but not FT, levels were significantly (p<0.05) higher in postmenopausal (12.07+/-0.40 microg/ml) than fertile women in the periovulatory period (10.46+/-0.36 microg/ml). In postmenopausal women, there was no significant correlation between TT and FT, nor between these tryptophan forms and gonadotropins, but only between FT and E2. Cluster analysis showed that the main cluster composed by FSH-LH-TT-FT observed in fertile women was absent in postmenopause, since both serum tryptophan forms were distant from gonadotropins. CONCLUSION: High TT levels circulate in postmenopausal women, with lack of correlation between TT and FT, and FT/TT and gonadotropins. Since estrogens play a pivotal role on central 5-HT metabolism, estrogen deprivation may alter the brain tryptophan utilization for 5-HT synthesis and its relation to gonadotropin release.     

Serotonin metabolism in normal pregnant women and fetus]

To evaluate serotonin (5-HT) metabolism in normal pregnant women and their fetuses, plasma free 5-HT, 5-hydroxyindoleacetic acid (5-HIAA). Tryptophan (TRP) and platelet free 5-HT content were determined by HPLC with electrochemical detection. Plasma free 5-HT and TRP concentrations and platelet 5-HT content in pregnant women did not change during pregnancy. In contrast, plasma free 5-HIAA increased after 30 weeks of gestation and reached its peak at 37 weeks. 5-HT, 5-HIAA and TRP concentrations in umbilical cord plasma were significantly higher than in maternal plasma. However, platelet 5-HT content in the fetus was significantly lower than in the mother. No significant correlation was found between 5-HT concentrations in maternal and cord plasma. However, a significant correlation was found between 5-HIAA, concentrations in maternal and cord plasma. The total 5-HT/TRP ratio in cord blood was significantly lower than in the maternal vein. The 5-HIAA/5-HT ratio in cord plasma was markedly higher than in maternal plasma. In conclusion, we demonstrated the patterns of plasma free 5-HT, 5-HIAA, TRP and platelet 5-HT concentrations in normal pregnant women and their fetuses. Furthermore, rapid 5-HT metabolism in the fetus was suggested.     

Dose-response analysis of effects of tibolone on climacteric symptoms

Objective To assess the clinically optimal tibolone dose for the relief of climacteric complaints.
Design A randomised, double blind, placebo-controlled trial.
Setting Twenty-eight centres in Norway, The Netherlands, Sweden and Finland.
Population Seven hundred and seventy-five healthy postmenopausal women were randomised to tibolone in a daily dose of 0.625, 1.25, 2.5 or 5.0 mg or placebo for 12 weeks.
Methods At baseline, and after 4, 8 and 12 weeks, hot flushes, sweating, vaginal bleeding and adverse experiences were recorded.
Main outcome measures Change in frequency and intensity of hot flushes and sweating over 12 weeks.
Results From week four onwards, 2.5 and 5.0 mg tibolone were significantly more effective than placebo, regarding the frequency of hot flushes and sweating (   P < 0.001  ), whereas the 0.625 mg dose was not significantly different from placebo during the study. The frequency of hot flushes with the 1.25 mg dose was statistically significantly different from placebo, only from week eight onwards. The incidence of dropouts due to insufficient therapeutic effect was much higher in the tibolone 1.25 mg group (9.5%) than in the 2.5 (1.9%) and 5.0 mg (1.3%) groups. A dose-related increase in incidence of vaginal bleeding or spotting was observed (   P < 0.0001  ). Bleeding incidence in the 5.0 mg dose group was about twice as high as in the 2.5 mg dose group. There was no difference in incidence of adverse experiences between the 2.5- and the 1.25 mg dose group.
Conclusion A daily dose of 2.5 mg tibolone is the clinically optimal dose for the treatment of climacteric complaints in postmenopausal women.     

Endocrinological analysis of climacteric symptoms and gonadal dysfunction by CRF test

Endocrinological studies on stressed climacteric women and some cases of gonadal dysfunction were carried out by analysing blood levels of adrenocorticotropic hormone (ACTH), beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) after the administration of synthetic corticotropin releasing factor (CRF, CRF test). Our results can be summarized as follows: 1. The responsiveness to CRF in perimenopausal and ovariectomized women rose and it corresponded with those of post gonadectomy in testicular feminization. 2. Responsiveness to CRF was decreased as estrogen levels decreased with the patient's age, and a similar tendency was observed in gonadal dysfunction. 3. Climacteric women with non-specific complaints have a higher responsiveness to CRF than that of postmenopausal women without complaints. Subjects with a high K.I score and with severe hot flush showed higher responsiveness to CRF than other subjects. These data suggest that CRF and its related hormones may be correlative with stress and hot flushes in climacteric periods and endogenous CRF may play an important psychosomatic role by regulating the hypothalamo-pituitary-adrenal function where there is decreased estrogen.