Essentials: How to Optimize Female Hormone Health for Vitality & Longevity | Dr. Sara Gottfried
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Overview
Andrew Huberman speaks with physician Sarah Gottfried about female hormones across the lifespan, emphasizing the interaction of genetics, environment, trauma, metabolism, nutrition, stress, reproductive health, and aging. Gottfried advocates “precision medicine”: establishing an individual baseline rather than relying only on population averages, then using symptoms and biomarkers to guide care.
The discussion covers age-specific hormone testing, menstrual-cycle timing, micronutrients and the microbiome, constipation and stress, polycystic ovary syndrome (PCOS), glucose and insulin monitoring, exercise, oral contraceptives, perimenopause, menopause, brain metabolism, and cardiovascular risk.
Key ideas
- Family history matters. Gottfried recommends asking mothers and grandmothers about hormonal conditions and trauma. She says intergenerational trauma may affect endocrine function, particularly cortisol signaling, while endometriosis, fibroids, and PCOS can have strong familial or genetic components.
- Hormonal assessment should change with age:
- During adolescence, menstrual cycles and estrogen-progesterone patterns may still be irregular because the reproductive system is maturing. Cortisol and signs of excess androgens may nevertheless be informative. Regularly cycling teenagers may be able to establish useful benchmarks.
- In the twenties and thirties, Gottfried favors establishing baseline estrogen, progesterone, testosterone, DHEA and related adrenal-androgen pathways, thyroid function, cortisol, estrogen metabolites, micronutrients, and metabolic health.
- She describes relatively high estrogen compared with progesterone as a possible contributor to fibroids and endometriosis, though the conversation does not define diagnostic thresholds or establish that hormone ratios alone predict these disorders.
- Testosterone may begin declining in women during their twenties—sometimes as early as age 28—at a rate Gottfried describes as approximately 1% per year. Rather than naming one ideal value, she generally favors the upper half of the laboratory’s normal range after age 25.
- Testing must be interpreted in menstrual-cycle context. If only one hormone measurement is possible in a woman with an approximately 28-day cycle, Gottfried suggests testing around cycle day 21–22, roughly one week before menstruation. As cycles shorten with age and progesterone production declines, testing may need to occur around day 19–20. Irregular cycles make timing harder.
- Blood testing is usually the cheapest and most likely to be insured, but Gottfried prefers dried-urine testing when available because it provides hormone-metabolite information rather than a brief blood-level snapshot. She combines blood and urine for micronutrient assessment.
- Hormonal contraception obscures the natural menstrual pattern, making it difficult to know what an individual’s untreated cycle and hormone production would otherwise be.
- Nutrition supports hormone production and metabolism. Gottfried highlights vitamins A and C, alpha-lipoic acid, plant-derived antioxidants, glutathione, B vitamins including folate/B9 and B12, and minerals—especially magnesium. Genetic variants may affect nutrient absorption or processing. Magnesium also participates in estrogen metabolism.
- Magnesium status should, in her view, be assessed using red-blood-cell or whole-blood magnesium rather than relying only on conventional serum measurement. The transcript gives an obviously malformed percentage for the prevalence of US magnesium deficiency, so no reliable prevalence estimate can be extracted from it.
- Vegetable and polyphenol intake during adolescence may be associated with breast-cancer risk decades later. Gottfried argues that showing teenagers objective micronutrient deficiencies could motivate dietary change during this potentially important period.
- For people who dislike vegetables, her preferred compromise is a smoothie about three times per week containing mild-tasting vegetables, such as frozen steamed broccoli or greens, combined with chocolate, vanilla, berries, or another acceptable flavor. Greens powders are convenient, but whole-food smoothies are preferred; supplements are a distant second.
- Gottfried sees bowel function as an important health signal. She reports constipation in roughly 80% of the women in her practice and connects it to multiple interacting factors: stress, borderline or overt thyroid dysfunction, estrogen-progesterone patterns, gut function, trauma, and neuroendocrine regulation.
- She states that women have higher population rates than men of depression, insomnia, multiple sclerosis, thyroid dysfunction, constipation, and certain forms of trauma. She cites the 1998 CDC-Kaiser Adverse Childhood Experiences studies, saying significant trauma affected about 50% of middle-aged men and 60% of women, with women more likely to report sexual abuse.
- Gottfried also claims that women’s gastrointestinal tracts are about 10 feet longer and that women more often have a tortuous colon, detectable during colonoscopy. These anatomical claims are presented in the conversation without supporting detail.
- Rather than trying to remove all stress, Gottfried focuses on reducing “perceived stress.” Useful approaches differ by individual and life stage. Her menu includes meditation, Transcendental Meditation, yoga, holotropic breathwork, sex, orgasm, connection, and feeling heard, seen, and loved.
- PCOS is heterogeneous and inconsistently diagnosed. Gottfried describes three commonly considered features:
- Polycystic-appearing ovaries. - Clinical hyperandrogenism, such as acne or hirsutism—unwanted male-pattern hair growth on areas such as the face, chest, or breasts. - Irregular or widely spaced periods, discussed as cycles extending to approximately 35 days or longer.
- Multiple diagnostic frameworks exist, so a woman may have PCOS without visible ovarian cysts if other features are present.
- PCOS is not solely a fertility disorder. Although irregular menstruation and difficulty becoming pregnant are often the presenting concerns, Gottfried says PCOS carries lifelong cardiometabolic implications, including after menopause. She considers elevated testosterone and other androgens important drivers of later cardiometabolic risk.
- In some PCOS phenotypes, hyperinsulinemia stimulates ovarian theca cells to overproduce testosterone. Insulin regulation is therefore central even when glucose still appears normal.
- Gottfried strongly favors continuous glucose monitors because immediate feedback can change behavior and give patients direct access to their own biological data. However, she considers glucose a relatively late marker: fasting and especially post-meal insulin may change years before glucose does. She invokes the Whitehall study in support of this sequence.
- She argues that greater patient access to biological data can shift medicine from a doctor-controlled disease-care model toward a more collaborative health model. Data do not replace clinicians, but can help patients understand their own responses.
- Major threats to vitality and longevity, in her view, include inadequate sleep, alcohol, high perceived stress, unsuitable foods, toxic relationships, social isolation, insufficient movement, and exercise that does not suit the individual.
- Exercise should match metabolic and stress physiology. Gottfried says people who produce more insulin or have poorer glucose control may require more activity to dispose of glucose. At the same time, extensive endurance exercise without sufficient resistance training—what she calls “chronic cardio”—may be associated with high cortisol, particularly among marathon runners.
- She says vitamin C may buffer some cortisol effects but does not present it as a substitute for changing an unsuitable exercise program.
- Gottfried describes her own experience at age 35: exhaustion, abdominal fat gain, and loss of sexual desire. Her physician offered oral contraception and an antidepressant. Her subsequent testing reportedly showed cortisol three times the expected level, fasting insulin in the twenties, glucose of 105, mildly abnormal thyroid function, and low progesterone.
- She concluded that running four miles three or four times weekly was aggravating her cortisol pattern. Replacing some running with Pilates, yoga, perceived-stress management, and changes to her supplements helped her. This is a personal case, not evidence that running is harmful to everyone.
- Oral contraceptives provide essential reproductive choice and have important benefits. Suppressing repeated ovulation reduces ovarian-cancer risk; Gottfried states that about five years of oral-contraceptive use is associated with an approximately 50% reduction in risk. Pregnancy and breastfeeding also create periods without ovulation and are associated with lower ovarian-cancer risk, while lifelong uninterrupted ovulation has been proposed as a risk factor.
- Ovarian cancer is difficult to diagnose early because symptoms are vague. Possible signs include persistent bloating, lower-abdominal fullness, or pressure, but these are common and nonspecific. Higher-risk women or those with a suspicious mass may be evaluated with gynecologic examination, ultrasound, and CA-125 testing, although neither CA-125 nor ultrasound is presented as an effective general early-screening method.
- Gottfried opposes routine prescription of oral contraceptives for acne, mildly painful periods, or other noncontraceptive reasons without a careful benefit-risk discussion. She suggests evaluating causes such as inflammation and considering alternatives, mentioning fish oil, specialized pro-resolving mediators, and sometimes aspirin during menstruation.
- Typical combined oral contraceptives contain ethinyl estradiol and a synthetic progestin rather than the progesterone naturally produced by the ovaries and adrenal glands. Gottfried links her concern about progestins to findings from the Women’s Health Initiative, although formulations and clinical contexts are not fully compared in the discussion.
- Potential oral-contraceptive effects she raises include depletion of magnesium and some B vitamins, microbiome changes, increased inflammatory tone, a possible association with inflammatory bowel disease or autoimmune conditions, altered thyroid function, and a more rigid hypothalamic-pituitary-adrenal stress response. She says studies she has seen report a two- to threefold rise in high-sensitivity C-reactive protein.
- Oral estrogen raises sex hormone-binding globulin (SHBG), which binds free estrogen and especially free testosterone. Many women may notice little effect, but Gottfried proposes that women with certain androgen-receptor characteristics, possibly involving CAG-repeat variation, may be unusually sensitive.
- Reduced free testosterone may be associated with vaginal dryness, lower libido, less muscle gain from resistance training, and possible changes in confidence, agency, and risk-taking. MBA-student studies are mentioned in relation to testosterone and risk-taking, but their design and applicability are not described.
- Gottfried calls testosterone the most abundant biologically active hormone in women and emphasizes its roles beyond sexuality, including muscle mass and behavioral traits.
- She states that oral contraceptives may reduce clitoral size by as much as 20%. She also cites a small or limited study by a researcher whose name she cannot fully recall, reporting that SHBG remained elevated one year after stopping the pill, though lower than during use. She explicitly says reversibility remains uncertain.
- Menopause preparation should begin before symptoms become severe. Baseline thyroid, estrogen, and progesterone measurements in the thirties may help contextualize later changes, although Gottfried does not aim to restore every hormone exactly to youthful levels.
- Perimenopause is the interval leading to the final menstrual period and may last around 10 years, depending partly on how closely symptoms are tracked. An early sign can be cycle shortening, such as a change from 28 to 25 days, sometimes beginning in the thirties or forties. Anxiety and sleep difficulty may also emerge and may involve estrogen-receptor signaling.
- Gottfried highlights Lisa Mosconi’s work at Cornell on female brain metabolism. Beginning around age 40, average cerebral glucose metabolism measured with FDG-PET reportedly declines by about 20% across the transition from premenopause through perimenopause to postmenopause.
- Women with more hot flashes, night sweats, and sleep disruption appear to show greater cerebral hypometabolism. Gottfried describes the subjective experience as “slow brain energy”: forgetfulness, reduced mental speed, and difficulty managing multiple tasks.
- She cautiously likens this to a low-level “pseudo-dementia” phenotype but does not say that ordinary perimenopausal cognitive symptoms are dementia. Mosconi’s research is presented as investigating whether midlife metabolic changes can identify later Alzheimer’s risk.
- Gottfried notes that both her mother and grandmother had Alzheimer’s disease. She and Huberman argue that insulin resistance and impaired brain fuel use may be important alongside genetics because neurons are highly metabolically demanding.
- Declining estrogen around ages 40–43 is proposed as a driver of cerebral hypometabolism. Gottfried believes some women may miss a potentially useful opportunity for menopausal hormone therapy because conventional practice often reserves it for severe hot flashes or night sweats.
- Hot flashes and night sweats should not be dismissed merely as nuisances. Gottfried describes them as biomarkers associated with cardiometabolic risk, accelerated bone loss, sleep disruption, and brain changes. She emphasizes that many perimenopausal symptoms reflect brain responses to hormonal change, not simply ovarian malfunction.
- Cardiovascular assessment is especially important because cardiovascular disease is the leading cause of death in women. Gottfried recommends obtaining a coronary artery calcium (CAC) score by age 45, or earlier with premature heart disease or substantial risk factors such as PCOS.
- A CAC score is obtained through a chest CT and quantifies calcified coronary plaque. A score of zero is reassuring at that moment, while an elevated score around age 45 may justify closer attention to cardiometabolic risk and prevention. Gottfried notes that testing may be self-ordered in some settings and may not routinely be offered by conventional physicians.
Practical takeaways
- Learn the maternal and grandmaternal history of endometriosis, fibroids, PCOS, thyroid disease, cardiovascular disease, Alzheimer’s disease, reproductive timing, and significant trauma.
- Track menstrual-cycle length, regularity, symptoms, contraception use, bowel frequency, sleep, stress, acne, unwanted hair growth, and changes in libido or cognitive function.
- Adolescents with signs of androgen excess or consistently irregular cycles may benefit from clinical evaluation, while women in their twenties or thirties may consider establishing clinician-interpreted hormonal, thyroid, metabolic, and nutritional baselines.
- Time reproductive-hormone tests to the cycle. For an approximately 28-day cycle, Gottfried’s preferred single testing point is around days 21–22; shorter cycles may require earlier testing. Irregular cycles need individualized timing.
- Consider fasting and post-meal insulin alongside glucose when evaluating metabolic risk. A continuous glucose monitor can reveal personal food, sleep, stress, and activity responses, but glucose data alone may miss earlier hyperinsulinemia.
- Prioritize varied vegetables, polyphenol-rich foods, and adequate micronutrients. If vegetables are difficult to tolerate, try blending mild vegetables or greens into a preferred smoothie several times weekly before relying on supplements.
- Match exercise to personal recovery and metabolic responses. Combine movement with appropriate resistance work, monitor signs of overreaching, and reconsider excessive endurance exercise if it consistently accompanies exhaustion or abnormal stress markers.
- Build a personalized set of perceived-stress tools rather than expecting one method to work for everyone. Options discussed include meditation, yoga, breathwork, intimacy, and supportive relationships.
- Discuss oral contraception as an individualized tradeoff: reproductive autonomy and lower ovarian-cancer risk versus possible hormonal, inflammatory, sexual, nutritional, and metabolic effects. Do not stop prescribed contraception or substitute aspirin or supplements without medical guidance.
- Treat persistent bloating, pelvic pressure, abnormal bleeding, markedly irregular cycles, hirsutism, or other concerning changes as reasons for clinical assessment rather than assuming they are normal hormonal symptoms.
- During the thirties and forties, watch for cycle shortening, new anxiety, disrupted sleep, hot flashes, night sweats, or cognitive slowing. These may mark perimenopause and warrant a broader discussion of bone, brain, and cardiometabolic health.
- Discuss CAC testing around age 45—or earlier with significant risk—with a qualified clinician, considering radiation exposure and whether the result would change management.
Caveats and limits
- The conversation reflects Gottfried’s clinical approach and interpretation of the evidence; it is not a systematic review, diagnostic protocol, or individualized medical plan.
- Several claims are presented without study details, absolute risks, reference ranges, or comparison with professional guidelines. These include preferred hormone levels, dried-urine testing, anatomical explanations for constipation, vitamin C for exercise-related cortisol, contraceptive effects on inflammation and clitoral size, and broad recommendations for CAC testing.
- Hormone values vary with age, cycle phase, contraception, pregnancy, laboratory method, illness, sleep, and medication use. A single result cannot reliably establish a diagnosis or “hormonal phenotype.”
- PCOS diagnostic language in the conversation is imprecise. Current assessment requires exclusion of other causes, and ovarian cysts are neither necessary in every diagnostic framework nor sufficient by themselves.
- Associations between symptoms, biomarkers, and later disease do not prove that treating the biomarker prevents the disease. Perimenopausal cerebral hypometabolism or cognitive slowing does not mean a woman will develop Alzheimer’s disease.
- Menopausal hormone therapy has potential benefits and risks that depend on age, timing, formulation, dose, route, symptoms, cardiovascular status, clotting risk, cancer history, and personal preferences. The discussion does not provide enough information to decide whether it is appropriate for any individual.
- Oral contraceptives vary considerably by estrogen dose, progestin type, and delivery method. Findings about one formulation or population may not apply to all hormonal contraception, and the long-term reversibility of some proposed effects remains uncertain.
- Aspirin, fish oil, specialized pro-resolving mediators, supplements, and hormone therapies can cause adverse effects or interact with medications. None should be started solely on the basis of this discussion.
- CA-125 and ultrasound are not reliable general screening tests for ovarian cancer in average-risk, asymptomatic women. Persistent or concerning symptoms require professional evaluation.
- CAC scanning involves radiation and does not detect all forms of coronary disease. Its value depends on baseline risk and whether the result will change preventive care.
- Population-level sex differences and trauma statistics do not determine any individual woman’s experience. Gottfried explicitly acknowledges generalizing at the population level, and some of her psychological interpretation of constipation is described as extending beyond established science.
中文翻译
概述
Andrew Huberman 与医生 Sarah Gottfried 探讨了女性一生中的激素变化，重点强调遗传、环境、创伤、代谢、营养、压力、生殖健康与衰老之间的相互作用。Gottfried 倡导“精准医学”：先建立个人基线，而不是仅依赖人群平均值，再利用症状和生物标志物指导医疗照护。
讨论涵盖了不同年龄阶段的激素检测、月经周期中的检测时机、微量营养素与微生物组、便秘与压力、多囊卵巢综合征（PCOS）、葡萄糖与胰岛素监测、运动、口服避孕药、围绝经期、绝经期、脑代谢以及心血管风险。
核心观点
- 家族史很重要。Gottfried 建议询问母亲和外祖母是否有激素相关疾病和创伤经历。她表示，代际创伤可能会影响内分泌功能，尤其是皮质醇信号传导；而子宫内膜异位症、子宫肌瘤和 PCOS 可能具有很强的家族性或遗传成分。
- 激素评估应随年龄变化：
- 在青春期，由于生殖系统尚在成熟，月经周期以及雌激素—孕酮模式可能仍不规律。尽管如此，皮质醇和雄激素过多的迹象仍可能提供有用信息。月经周期规律的青少年或许可以建立有用的基准。
- 在二十多岁和三十多岁时，Gottfried 主张建立雌激素、孕酮、睾酮、DHEA 及相关肾上腺—雄激素通路、甲状腺功能、皮质醇、雌激素代谢物、微量营养素和代谢健康的基线。
- 她将相对于孕酮较高的雌激素描述为子宫肌瘤和子宫内膜异位症的一个可能促成因素，不过这次谈话并未界定诊断阈值，也未证实仅凭激素比值就能预测这些疾病。
- 女性的睾酮可能从二十多岁开始下降——有时早至 28 岁——Gottfried 描述的下降速度约为每年 1%。她没有提出一个统一的理想数值，而是总体上倾向于让 25 岁以后女性的数值处于实验室正常范围的上半区。
- 检测结果必须结合月经周期背景来解读。对于月经周期约为 28 天的女性，如果只能测量一次激素，Gottfried 建议在周期第 21～22 天左右进行检测，也就是月经前约一周。随着年龄增长，周期缩短且孕酮生成减少，检测可能需要提前到第 19～20 天左右。周期不规律会使检测时机更难确定。
- 血液检测通常最便宜，也最有可能获得保险报销，但在条件允许时，Gottfried 更倾向于使用干尿检测，因为它能提供激素代谢物信息，而不是短暂时点的血液浓度快照。她会结合血液和尿液进行微量营养素评估。
- 激素避孕会掩盖自然月经模式，因此很难得知一个人在未接受激素干预时的月经周期和激素生成原本会是什么样。
- 营养支持激素的生成和代谢。Gottfried 强调维生素 A 和 C、α-硫辛酸、植物来源的抗氧化剂、谷胱甘肽、包括叶酸/B9 和 B12 在内的 B 族维生素，以及矿物质——尤其是镁。遗传变异可能影响营养素的吸收或处理。镁也参与雌激素代谢。
- 她认为，镁状态应通过红细胞镁或全血镁进行评估，而不应只依赖常规血清检测。原始谈话在提及美国镁缺乏流行率时给出了一个明显错误的百分比，因此无法从中提取可靠的流行率估计。
- 青春期的蔬菜和多酚摄入量可能与数十年后的乳腺癌风险有关。Gottfried 认为，向青少年展示客观存在的微量营养素缺乏，可能会促使他们在这一可能很重要的时期改变饮食。
- 对于不喜欢蔬菜的人，她更偏好的折中方案是每周约三次饮用冰沙，其中加入味道温和的蔬菜，例如冷冻熟西兰花或绿叶蔬菜，并搭配巧克力、香草、浆果或其他可以接受的口味。绿叶蔬菜粉很方便，但她更倾向于使用完整食物制作的冰沙；补充剂则远远排在其后。
- Gottfried 将排便功能视为一个重要的健康信号。她报告称，其诊所中约 80% 的女性存在便秘，并将其与多个相互作用的因素联系起来：压力、临界或明确的甲状腺功能异常、雌激素—孕酮模式、肠道功能、创伤以及神经内分泌调节。
- 她表示，在人群层面，女性的抑郁症、失眠、多发性硬化、甲状腺功能异常、便秘以及某些形式创伤的发生率均高于男性。她援引了 1998 年 CDC-Kaiser 不良童年经历研究，称约 50% 的中年男性和 60% 的女性曾受到重大创伤影响，而女性更可能报告遭受过性虐待。
- Gottfried 还声称，女性的胃肠道约长 10 英尺，而且女性更常出现迂曲结肠，可在结肠镜检查时发现。这些解剖学说法在谈话中并未附带支持性细节。
- Gottfried 并不试图消除所有压力，而是专注于降低“感知压力”。有效的方法因个人和人生阶段而异。她列举的方法包括冥想、超觉静坐、瑜伽、整体呼吸法、性行为、高潮、建立联结，以及感受到自己被倾听、被看见和被爱。
- PCOS 具有异质性，诊断也不一致。Gottfried 描述了通常会考虑的三个特征：
- 卵巢呈多囊样外观。 - 临床高雄激素表现，例如痤疮或多毛症——在面部、胸部或乳房等部位出现不受欢迎的男性型毛发生长。 - 月经不规律或间隔很长，谈话中指周期延长至约 35 天或更久。
- 目前存在多种诊断框架，因此，如果具备其他特征，即使看不到卵巢囊肿，女性也可能患有 PCOS。
- PCOS 不仅仅是一种生育障碍。虽然月经不规律和难以怀孕通常是患者就诊时最关心的问题，但 Gottfried 表示，PCOS 会带来终身的心脏代谢影响，包括绝经后仍然存在。她认为，睾酮及其他雄激素升高是日后心脏代谢风险的重要驱动因素。
- 在某些 PCOS 表型中，高胰岛素血症会刺激卵巢卵泡膜细胞过量生成睾酮。因此，即使葡萄糖水平看起来仍然正常，胰岛素调节也至关重要。
- Gottfried 非常支持使用连续葡萄糖监测仪，因为即时反馈可以改变行为，并让患者直接获取自己的生物学数据。不过，她认为葡萄糖是一个相对较晚才发生变化的标志物：空腹胰岛素，尤其是餐后胰岛素，可能比葡萄糖早数年出现变化。她援引 Whitehall 研究来支持这一变化顺序。
- 她认为，让患者更多地获取自己的生物学数据，可以推动医学从由医生控制的疾病照护模式转向更具协作性的健康模式。数据不能取代临床医生，但可以帮助患者了解自身的反应。
- 在她看来，活力和长寿面临的主要威胁包括睡眠不足、饮酒、感知压力过高、不合适的食物、有害的人际关系、社会孤立、运动量不足，以及不适合个人情况的锻炼。
- 运动应与个人的代谢和压力生理相匹配。Gottfried 表示，胰岛素分泌更多或葡萄糖控制较差的人，可能需要更多活动来处置葡萄糖。与此同时，在缺少足够抗阻训练的情况下进行大量耐力运动——她称之为“慢性有氧运动”——可能与高皮质醇有关，尤其是在马拉松跑者中。
- 她表示，维生素 C 可能缓冲皮质醇的部分影响，但并未将其描述为改变不合适运动方案的替代措施。
- Gottfried 描述了自己 35 岁时的经历：精疲力竭、腹部脂肪增加以及性欲丧失。她的医生向她提供了口服避孕药和抗抑郁药。她后来所做的检测据称显示，皮质醇达到预期水平的三倍，空腹胰岛素处于二十多的范围，葡萄糖为 105，甲状腺功能轻度异常，且孕酮偏低。
- 她得出结论，自己每周跑三到四次、每次四英里的习惯加重了皮质醇模式。用普拉提、瑜伽、感知压力管理和调整补充剂取代一部分跑步后，她的状况有所改善。这是一个个人案例，并不能证明跑步对所有人都有害。
- 口服避孕药提供了不可或缺的生育选择权，并具有重要益处。抑制反复排卵可以降低卵巢癌风险；Gottfried 表示，使用口服避孕药约五年与风险降低约 50% 相关。怀孕和母乳喂养也会形成不排卵的时期，并与较低的卵巢癌风险相关；而终生不间断排卵则被提出可能是一项风险因素。
- 卵巢癌很难早期诊断，因为其症状模糊。可能的迹象包括持续腹胀、下腹部饱胀感或压迫感，但这些症状很常见且缺乏特异性。风险较高的女性或存在可疑肿块者，可能会接受妇科检查、超声检查和 CA-125 检测，不过谈话并未将 CA-125 或超声描述为有效的普通人群早期筛查方法。
- Gottfried 反对在没有仔细讨论获益与风险的情况下，常规为痤疮、轻度痛经或其他非避孕原因开具口服避孕药。她建议评估炎症等潜在原因并考虑替代方案，其中提到了鱼油、专门促炎症消退介质，有时还包括月经期间使用阿司匹林。
- 典型复方口服避孕药含有炔雌醇和合成孕激素，而不是由卵巢和肾上腺自然生成的孕酮。Gottfried 将她对合成孕激素的担忧与女性健康倡议研究的发现联系起来，不过谈话并未全面比较不同制剂和临床情境。
- 她提出的口服避孕药潜在影响包括镁和某些 B 族维生素的耗竭、微生物组变化、炎症状态升高、可能与炎症性肠病或自身免疫性疾病相关、甲状腺功能改变，以及下丘脑—垂体—肾上腺应激反应变得更为僵化。她表示，自己看过的研究报告高敏 C 反应蛋白升高至原来的两到三倍。
- 口服雌激素会升高性激素结合球蛋白（SHBG），后者会结合游离雌激素，尤其是游离睾酮。许多女性可能几乎察觉不到影响，但 Gottfried 提出，具有某些雄激素受体特征的女性可能异常敏感，其中可能涉及 CAG 重复序列变异。
- 游离睾酮减少可能与阴道干燥、性欲降低、抗阻训练后肌肉增长较少，以及自信、能动性和冒险倾向可能发生变化有关。谈话提到了关于 MBA 学生的睾酮与冒险行为研究，但没有说明其研究设计和适用性。
- Gottfried 将睾酮称为女性体内含量最丰富的生物活性激素，并强调其在性功能之外的作用，包括肌肉量和行为特征。
- 她表示，口服避孕药可能使阴蒂大小最多缩小 20%。她还援引了一项规模较小或证据有限的研究，但无法完整回忆起研究者的姓名；该研究报告称，停药一年后 SHBG 仍然偏高，不过低于服药期间。她明确表示，其可逆性仍不确定。
- 应在症状变得严重之前开始为绝经做准备。三十多岁时测量甲状腺、雌激素和孕酮基线，可能有助于理解之后的变化，不过 Gottfried 并不主张把每一种激素都完全恢复到年轻时的水平。
- 围绝经期是最终一次月经之前的一段时期，可能持续约 10 年，部分取决于对症状追踪得有多细致。早期迹象可能包括周期缩短，例如从 28 天变为 25 天，有时从三十多岁或四十多岁开始。焦虑和睡眠困难也可能出现，并可能涉及雌激素受体信号传导。
- Gottfried 强调了 Lisa Mosconi 在 Cornell 开展的女性脑代谢研究。据报告，从约 40 岁开始，在从绝经前期经过围绝经期到绝经后期的过渡过程中，通过 FDG-PET 测得的平均脑葡萄糖代谢下降约 20%。
- 出现更多潮热、盗汗和睡眠中断的女性，似乎会表现出更明显的脑代谢减退。Gottfried 将主观体验描述为“脑能量变慢”：健忘、思维速度下降，以及难以同时处理多项任务。
- 她谨慎地将其比作一种低程度的“假性痴呆”表型，但并未声称普通的围绝经期认知症状就是痴呆。Mosconi 的研究被描述为正在探讨中年时期的代谢变化能否识别日后的阿尔茨海默病风险。
- Gottfried 指出，她的母亲和外祖母都患有阿尔茨海默病。她和 Huberman 认为，除遗传因素外，胰岛素抵抗和脑燃料利用受损也可能很重要，因为神经元具有极高的代谢需求。
- 40～43 岁左右雌激素下降被提出可能是脑代谢减退的驱动因素。Gottfried 认为，一些女性可能错过了使用绝经期激素治疗的潜在有利时机，因为传统医疗实践往往只在出现严重潮热或盗汗时才考虑这种治疗。
- 不应仅仅把潮热和盗汗视为令人烦恼的小问题。Gottfried 将其描述为与心脏代谢风险、骨质加速流失、睡眠中断和脑部变化相关的生物标志物。她强调，许多围绝经期症状反映的是大脑对激素变化的反应，而不只是卵巢功能异常。
- 心血管评估尤其重要，因为心血管疾病是女性的首要死因。Gottfried 建议最迟在 45 岁时获取冠状动脉钙化（CAC）评分；如有早发心脏病或 PCOS 等重大风险因素，则应更早检测。
- CAC 评分通过胸部 CT 获得，用于量化冠状动脉钙化斑块。评分为零在当时具有安慰意义，而在约 45 岁时评分升高，可能意味着需要更加关注心脏代谢风险和预防。Gottfried 指出，在某些地方可以自行申请检测，而传统临床医生可能不会常规提供这项检测。
实际要点
- 了解母亲和外祖母的子宫内膜异位症、子宫肌瘤、PCOS、甲状腺疾病、心血管疾病、阿尔茨海默病、生育时间以及重大创伤史。
- 追踪月经周期长度、规律性、症状、避孕药使用情况、排便频率、睡眠、压力、痤疮、不受欢迎的毛发生长，以及性欲或认知功能的变化。
- 有雄激素过多迹象或周期持续不规律的青少年可能会从临床评估中获益；二十多岁或三十多岁的女性则可以考虑建立由临床医生解读的激素、甲状腺、代谢和营养基线。
- 根据月经周期安排生殖激素检测。对于约 28 天的周期，Gottfried 偏好的单次检测时点是第 21～22 天左右；周期较短时可能需要提前检测。周期不规律者需要个体化确定时机。
- 评估代谢风险时，应考虑在葡萄糖之外检测空腹和餐后胰岛素。连续葡萄糖监测仪可以揭示个人对食物、睡眠、压力和活动的反应，但仅靠葡萄糖数据可能会漏掉更早出现的高胰岛素血症。
- 优先摄入多样化蔬菜、富含多酚的食物以及充足的微量营养素。如果难以耐受蔬菜，可以先尝试每周数次把味道温和的蔬菜或绿叶蔬菜加入自己喜欢的冰沙中，再考虑依赖补充剂。
- 根据个人恢复情况和代谢反应调整运动。将日常活动与适当的抗阻训练相结合，监测过度训练的迹象；如果过量耐力运动持续伴随精疲力竭或异常的压力标志物，应重新考虑这种运动方式。
- 建立一套个性化的感知压力管理工具，而不要期待一种方法适用于所有人。讨论到的选择包括冥想、瑜伽、呼吸练习、亲密关系和支持性人际关系。
- 将口服避孕视为需要个体化权衡的问题：一方面是生育自主权和较低的卵巢癌风险，另一方面是可能存在的激素、炎症、性功能、营养和代谢影响。不要在没有医疗指导的情况下停用处方避孕药，也不要自行改用阿司匹林或补充剂。
- 如果持续腹胀、盆腔压迫感、异常出血、月经周期明显不规律、多毛症或出现其他令人担忧的变化，应将其视为需要临床评估的理由，而不是想当然地认为它们是正常的激素症状。
- 在三十多岁和四十多岁期间，留意月经周期缩短、新出现的焦虑、睡眠中断、潮热、盗汗或认知速度减慢。这些可能标志着围绝经期，并值得就骨骼、大脑和心脏代谢健康进行更广泛的讨论。
- 与具备资质的临床医生讨论在约 45 岁时进行 CAC 检测；如存在重大风险，则应更早讨论，同时考虑辐射暴露以及检测结果是否会改变管理方案。
注意事项与局限
- 这次谈话反映的是 Gottfried 的临床方法和她对证据的解读；它不是系统综述、诊断方案或个体化医疗计划。
- 有若干说法在提出时没有提供研究细节、绝对风险、参考范围或与专业指南的比较。其中包括偏好的激素水平、干尿检测、对便秘的解剖学解释、使用维生素 C 应对运动相关皮质醇、避孕药对炎症和阴蒂大小的影响，以及广泛推荐 CAC 检测。
- 激素数值会随年龄、周期阶段、避孕措施、妊娠、实验室方法、疾病、睡眠和用药情况而变化。单次结果无法可靠地确立诊断或“激素表型”。
- 谈话中关于 PCOS 的诊断用语并不精确。目前的评估需要排除其他原因；在部分诊断框架中，卵巢囊肿并非必要条件，而其单独存在也不足以确诊。
- 症状、生物标志物与日后疾病之间的关联，并不能证明治疗该生物标志物就能预防疾病。围绝经期脑代谢减退或认知速度减慢，并不意味着女性将会患上阿尔茨海默病。
- 绝经期激素治疗具有潜在获益和风险，具体取决于年龄、时机、制剂、剂量、给药途径、症状、心血管状况、凝血风险、癌症病史和个人偏好。这次讨论没有提供足够信息来判断该治疗是否适合任何特定个人。
- 口服避孕药在雌激素剂量、合成孕激素类型和给药方式方面存在很大差异。针对某一种制剂或某个人群的研究结果可能不适用于所有激素避孕方式，而且某些被提出的影响在长期内是否可逆仍不确定。
- 阿司匹林、鱼油、专门促炎症消退介质、补充剂和激素治疗可能引起不良反应或与药物相互作用。任何人都不应仅根据这次讨论开始使用这些产品或治疗。
- 对于平均风险且无症状的女性，CA-125 和超声并不是可靠的卵巢癌普通筛查方法。持续存在或令人担忧的症状需要专业评估。
- CAC 扫描涉及辐射，而且不能检出所有形式的冠状动脉疾病。其价值取决于基线风险，以及检测结果是否会改变预防性照护。
- 人群层面的性别差异和创伤统计数据并不能决定任何一位女性的个人经历。Gottfried 明确承认自己是在进行人群层面的概括，而她对便秘的某些心理学解释也被描述为超出了现有科学所确立的范围。
Full transcript
Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Sarah Gottfried. Dr. Gottfried, Sarah, welcome. Thank you. So happy to be here. Yeah, I'm delighted and very excited to ask you about an enormous number of topics. You are expert in so many things, female hormones in particular. Is it ever informative for a woman, regardless of age, to know something about her mother's, perhaps even her grandmother's, experience vis-a-vis hormones? What sorts of conversations should women be having with themselves and with family members to get a window into what their specific needs might be?
So my work is really at the interface between genetics and environment. And I think it's essential that you understand what your grandmother went through, and especially your mother. So I would probably start first with trauma and intergenerational trauma, because I think that affects the endocrine system so hugely, especially cortisol signaling. And then there's certain female conditions that have a very strong component genetically, most of which run in my family. So that includes endometriosis, fibroids, and polycystic ovarian syndrome. Maybe we could march through and just say, for a woman in her teens who's already hit puberty, what sorts of biomarkers should those young women be paying attention to, likewise for women in their 20s, 30s, maybe we could take it more or less by decade, starting at puberty.
In your teenage years, what I think is really interesting is to look at cortisol, to look at the dance between estrogen and progesterone in those years, is less helpful because I think there's a lot of variability due to the immaturity of the system. If you've got someone who's got really regular periods, it's probably better to do some benchmarking at that age. But generally I find that benchmarking is best performed in your 20s or 30s. Are periods not that regular in terms of duration of the menstrual cycle when the menstrual cycle first sets in? For a lot of women, they're not regular.
And then there's the whole piece of oral contraceptives and other forms of contraception, where you have no idea what the normal cycle is. But getting back to your original question, which is about biomarkers per decade, in your 20s, that's when you wanna do some base casing with estrogen, progesterone, and testosterone. What happens a lot of the time is that estrogen dominates in that tango. And when that happens, it sets you up for greater risk of fibroids, endometriosis. I'd want to know about DHEA and sort of the whole Anderson pathway. I'd want to know about the metabolites of estrogen because some of them are protective and very helpful.
Others are a bit like Homer Simpson. I mean, they are just like causing all kinds of problems in your body. I'd also like to know about their stool. So I want to know about the microbiome. In terms of blood testing or various tests for these other biomarkers, getting estrogen and testosterone and other ratios, women will need to do it at different stages of their menstrual cycle. If they had to pick one, either in the follicular phase or in the luteal stage of their ovulatory menstrual cycle, when would you suggest they do that? So if you forced me to pick one, I would say probably day 21 to 22 for someone in their twenties.
So for most women, they've got a menstrual cycle date that averages out at 28 days. So this is about a week before they start their period. For women who are more irregular, it's harder to do that. As women get older, usually the cycle gets a little shorter. So as they start to decline in their progesterone production, their period gets a little closer together. At that point, you want to test sooner, like day 19, 20. Blood test is the cheapest thing. It's usually what's covered by insurance, but my preference would be to do dried urine so that I get metabolomics in addition to the levels of these hormones.
And if I'm forced to, I'll use blood testing. It's not as comprehensive. And as you know, it's a quick little snapshot while the needle's in your vein for 30 seconds. Let me go back and say one other thing about biomarkers. A big part of the testing that I do in phenotyping my patients, I practice precision medicine. I like to almost start with nutritional testing. That would be potentially a helpful thing to do in your 20s. Becomes less important as you get older and you develop more micronutrient deficiencies, but micronutrients play a huge role terms of hormone production. Magnesium is hugely involved in the way that you get rid of estrogen, as an example. So micronutrient testing, what I usually do is a combination of blood and urine.
And so I'm looking at all of the micronutrients that we can measure that have some clinical scientific basis behind them. Intake of vegetables, polyphenols, is such an important predictor a future risk of breast cancer, like when you're 50, 60 plus. And the most important time is when you're a teenager. If you have evidence that you could show a 17 year old that they've got micronutrient gaps, I think that would be a motivator for them to eat differently at a time when it's so critical, even though it's 25 years in the future that it's gonna potentially change this arc that they're on.
What do you do for a young woman who doesn't like vegetables or is not somehow able or willing to get those five colors a day of vegetable to help support the microbiome? What other sorts of tools behavioral or otherwise are useful? What I try to get them to do is have a smoothie. If I could get them to have a smoothie three times a week and to throw some of these vegetables in, that makes a huge difference. I mean, we know that makes a difference in terms of microbiome change. Like I have them do steam broccoli that's in the freezer because it's got very little taste.
They could do that in a chocolate smoothie. They could add some greens. I like greens. Powders are super convenient. So that with kind of a taste that they like, whether that's chocolate, which is what most of my clients want, or vanilla with berries and that sort of thing. So that can go a long way if you don't like vegetables. And short of that, I would say some supplements, but I would say that's a distant second to making a smoothie. What is going to be the best way to test the microbiome? What I like to do with nutritional testing is run a panel that's looking at antioxidants.
So like vitamin A, vitamin C, alpha lipoic acid, plant-based antioxidants, because you can measure that in the blood. I like to look at some of the key vitamins, especially the B vitamin range, because as you probably know, If you've got particular genetic polymorphism, so you might be less likely to be absorbing the right level of vitamin B9, folate, vitamin B12, et cetera. I'm also looking, going back to the antioxidants, at glutathione, because I think that's such an important lever. And then I'm looking at some of the minerals. Magnesium is really the most important. And we know that somewhere around 788% of Americans are deficient in magnesium.
That's like the lowest hanging fruit. I would be curious, for instance, like with magnesium, if that number of people are deficient, Does that mean that that number of people should be targeting their nutrition towards foods that contain magnesium and or supplementing with magnesium? And if so, what forms of magnesium? You have to measure red blood cell magnesium, like whole blood. And with deficiency, it's interesting with supplementation for my patients who tend toward constipation, and that's frankly about 80% of the women that I take care of. Really? Yes. Wow. I'm curious as to why that is. Patriarchy, rage, the pine system.
Right, psychology, immunology, neural and endocrine factors combined, is that? Yes, and then I would say there's another factor. Being female is a health hazard. So we have twice the rate of depression, insomnia. We've got three to four X increased risk of multiple sclerosis. We've got five to eight times the risk of thyroid dysfunction. So if you just look at that and you look at subtle preclinical thyroid dysfunction, a large number of the women that I take care of have thyroid dysfunction that's contributing to constipation. And if we go back to that control system, nipatholamic pituitary adrenal, thyroid, canal, gut axis, and they have a lot of perceived stress together with this borderline thyroid function that no mainstream medicine doctor has told her is a problem.
And then she's got a problem with the tango between estrogen and progesterone. She's gonna tend toward constipation. Women have a lot more constipation than men. The gut is about 10 feet longer in women compared to men. And they are much more likely to have a torturous colon. And the way you know that is you get a colonoscopy. Women experience more trauma than men. This is well-established. If you look at the ACE studies that were done by the CDC and Kaiser in 1998, we know that men for the most part, middle aged men have about 50% of them experience significant trauma as defined by the ACE questionnaire.
Women are at 60%. And that's pretty durable since 1998. They have different forms of abuse, much more likely to have sexual abuse. They have a different HPA response than men. Their perceived stress tends to be higher, and I'm generalizing for a population. And so if you look at the physiology of a female, I think that constipation and that need to let control and restrain and hold things in, I think that's part of the physiology. So I'm veering away from the science, but I do think that it is a really important signal to pay a lot of attention to. What sorts of tools do you recommend people use to relieve constipation? Sounds like reducing stress is going to be a huge one.
Yes. What are your favorite stress reduction tools, things that can really lower the baseline? So I'm not a fan of lowering stress. I'm a fan of lowering perceived stress. I think all of us need an a la carte menu of what is most effective. So what works for me now at my age is different than the TM I did as a college student, Transcendental Meditation. I became a certified yoga teacher when I was in my 30s. That is very effective for a lot of people. I do holotropic breath work. I think people are starting to appreciate that there are ways that they can relieve their stress that don't only fall under the categories of vacation.
Right. And meditation. But I want to say that meditation is obviously a wonderful tool. Well, certainly it's a great tool and it's got such a scientific basis behind it. But there's so many things on this a la carte menu, sex, orgasm, connection, feeling heard and seen and loved. I want to use this as an opportunity to, A, keep this in mind as we turn to a question that I didn't close the hatch on earlier and it's my fault, which is I'm now clear on the fact that a woman in her late teens, early twenties ought to know something about her testosterone, estrogen, thyroid, cortisol levels should start at least thinking about her microbiome, should be thinking about how many bowel movements and the timing of those bowel movements per day.
And I'm assuming that what I just described is also true for women in their 20s, 30s, 40s, 50s on up to hundreds. Is that correct? That's correct. But I would say that there are differential opportunities by decade. So I'm glad you circled it back to teenagers and testosterone, because I think if you know, for instance, in your teenage years, that you have a high androgens and that you've got this potential phenotype way into the future that you may not even notice. I mean, maybe you notice you've got a few extra hairs on your chin or something. If you know that your testosterone is elevated or some other androgen, it might change the arc of how you take care of yourself.
So I think that could be very helpful in your teenage years. In your 20s, for people who are a stress case like me, so age 27 on the wards at UCSF, if I had known that I was such a high cortisol person, I think I would have done things differently. I would have changed my behavior. Your testosterone can decline starting in your 20s, kind of depending on how much stress your matrix is under. So for women that can start as early as 28, usually your testosterone declines by about 1% per year. What level of testosterone do you like to see in a woman once she's sort of post, let's say after age 25.
So the way I tend to describe this on podcasts is the top half of the normal range. I get a lot of questions about PCOS. Yeah. So PCOS is one of those really poorly understood conditions. It kind of flies below the radar until a woman wants to get pregnant or she's got some other issue that drives her to a physician. The problem is that it is a syndrome, right? So polycystic ovary syndrome, sometimes polycystic ovarian syndrome and syndromes don't necessarily fit together into a really clear diagnostic criteria. So, in this instance, there are three different criteria that we look for.
So, it's just on the ovaries, having clinical manifestations of hyperandrogenism, so that could be Hercetism, Acne, other things, and then usually irregular periods. And the way that that's defined, at least by the latest criteria, is having a period every 35 days or less. So, typical cycle length, 28 days, 35 days, you know, you're skipping a period here and there. So those are the criteria that we use to diagnose PCOS. There are about four different systems out there in the literature for diagnosing PCOS, which is where it starts to get confusing. So there's some women who have no cysts on their ovaries, but they've got heresitism and they've got irregular periods. Could you define heresitism?
Heresitism is increased hair growth, usually in places that you don't want it. So for women, it can be, you know, kind of male pattern, they might notice it on their breasts, on their chest. What we know is that PCOS is not just a problem in terms of irregular periods and then difficulty getting pregnant. So those are mostly problems in your 20s, 30s, early 40s, but it is a massive risk factor for cardiometabolic disease as you get older. So many people tend to pitch and hold PCOS as a problem of reproductive age. We have to be thinking of it over the entire female life cycle. And I would say it's even more important to consider it over the age of 50, you know, average age of menopause is 51 to 52, because we know that that elevated testosterone, the high androgens, are probably the greatest cardiometabolic driver of disease for women with PCOS. The thread we haven't talked about is the role of insulin and glucose. So for some of the phenotypes of PCOS, the problem is hyper insulinemia, high insulin in the blood is driving those theca cells and the ovaries to overproduce testosterone. Are you a fan of continuous glucose monitors? The hugest, most gigantic fan of CGM's.
I've never seen any tool that I've ever used in medicine change behavior the way that CGM's do. like, I think really understanding what the mediators are of your glucose control is essential. Now that said, it's also kind of a later effect. I mean, I'd rather know your insulin. And we know from the Whitehall study that insulin, especially postprandial insulin, fasting insulin too, can change years and years before you get a change in glucose. So, that's more for prediabetes and diabetes. Third thing is it democratizes data. One of the most hopeful and exciting things that I'm seeing right now in the health space is that we're going from this patriarchal relationship where doctors hold the power and are the gatekeepers of data, to patients and clients having much more access to that enchantment about their own chemistry and their own biology, teaching the patient to be their own clinician.
To me, that is a loop of benevolence and integrity that I think is essential to creating health. We've got a disease care system. We need the democratization of data to become a health-based system. If you add a magic wand and you could give two or three don'ts to maximize vitality and longevity, let's focus first on female patients. But if it extends to male patients as well, what would you like to see them not do? So I would say sleep, alcohol, high perceived stress, eating the wrong foods, toxic relationships and isolation. And then number six, not moving enough for not moving and exercising in a way that really fits with your body.
So those- So we start with that one actually, just cause it's such a, and then work backwards. Yeah, well, I think for me, because I have a phenotype that produces a lot of insulin, kind of depending on how I'm on my game, I have a lot of glucose, so I have to exercise a lot more to dispose that glucose. So I think you then have to move from medicine for the population or prescriptions for the population to what works for the individual. One of the mediators that I think is important, especially for people who do what I call chronic cardio, which is what I did, is cortisol.
So we know that runners, especially marathon runners, people who do a lot of cardio and don't do much resistance training, they tend to have much high cortisol levels. And you can buffer that with vitamin C, vitamin C can decrease the effect, but chronic cardio doesn't always serve people. When I first started measuring hormone panels in myself, I went to my physician and I said, I'm 35. I've never been so exhausted in my life. I just feel like I'm pushing a rock up the hill. I've got this belly fat that I don't like and I don't want to have sex with my husband.
What can we do about this? And he offered a birth control pill and an antidepressant. Goodness. So I left him and I went to the lab and I ran a hormone panel and my cortisol was three times it should have been. My insulin was in the twenties. I was fasting. My glucose was 105. My thyroid was mildly abnormal. My progesterone was low. And that set me on this course of realizing that what I was doing as a physician, taking care, especially of women, was not getting to some of these root causes that are so essential. And I would say I had to start first with cortisol.
At that time I was running four miles, three times a week, four times a week. That was just racing my cortisol further. So that was not the right exercise for me. I needed more adaptive exercise. I started doing Pilates, more yoga. That helped to lower my cortisol. I mean, it started me on changing the way I was managing perceived stress and it also changed my supplement Richmond. I'd like to make sure that we circle back to birth control. In particular, oral contraceptive birth control. What are your concerns? What do you like about oral contraceptives? What do you dislike about them?
In terms of benefit, I think that, especially when they first came out and even now, it gives women reproductive choice and that's essential. So I'm a big fan in that regard, and we've got a lot of data to show both the risks and also the benefits of it. So I'll speak first into the benefits because I'm going to get on a soapbox a little bit about the risks. So we know that it reduces the risk of ovarian cancer. So there's something about this idea of incessant ovulation that is not good for the female body. So if you look at, for instance, women who are nuns, who don't take oral contraceptives and they have a period every single month of their reproductive lives, they have a greater risk of ovarian cancer.
So if you look then at women who have several babies and they've got a period of time when they're pregnant that they're not ovulating and then they breastfeed for some period of time, they have a lower risk of ovarian cancer. So oral contraceptives help with reducing ovulation and reducing risk. We know that if you take the oral contraceptive for about five years, it reduces your risk of ovarian cancer by 50%. And that's significant because we're so poor at diagnosing ovarian cancer early. There's really no method that's really effective. We use CA125 and ultrasound screening, especially in women who are at greater genetic risk.
But even that, often we diagnose it in a later stage. Maybe just because that statement is gonna highlight for a number of people the question of what are some of the earliest symptoms that people can recognize without a blood test? So is ovarian cancer, is it gonna be pain? So the problem is the symptoms are so vague and they're so nonspecific. One of the most common symptoms is bloating. And we've already talked about constipation. We've talked about how women have this longer track, GI track. And so bloating is a really common experience for most women. You can have bulk symptoms, feeling like your lower belly is kind of pressed out.
The way that we inform women in terms of watching for this is to get regular gynecologic exams for women who are at high risk or they have, for instance, an ultrasound for some reason and it shows a mass that we're concerned about. There's a way to triage that in terms of what kind of evaluation that they need. And that's the situation where you might get a blood test called the CA125. Taking estrogen and thereby reducing the frequency of ovulation lowers the risk of ovarian cancer. Should women that are, even women who are not sexually active, so they're not actively trying to get pregnant or avoid getting pregnant, but if they're not sexually active, would they be wise to suppress ovulation for periodically using hormone-based contraception just so that they can offset the risk of ovarian cancer?
That's a very rational question. And I would say that's what mainstream medicine has had at its back to recommend oral contraceptives, not just for women who are seeking contraception, but for acne, for painful periods, for really kind of the drop of a hat, they're prescribing oral contraceptives. That's what I was taught to do. And I think a lot of that is pharmaceutical influence. The oral contraceptive is two hormones. It's ethanol estradiol, and it's a progestin. So it's not the normal progesterone that your body makes, that your ovaries make, and your adrenals make. It is a synthetic form of progesterone. And it is the same progesterone, similar, same class, that was shown to be dangerous and provocative in the women's health initiative.
So I'm not a fan of progestins. I do not recommend them for any woman, unless it gives them some freedom in some way. So like with almost any pharmaceutical, the oral contraceptive depletes certain micronutrients. Magnesium, there's certain vitamin Bs that are depleted. It also affects the microbiome. That data is not as strong, but there seems to be some effect and there's also an increased risk of inflammatory bowel disease and autoimmune condition. it increases inflammatory tone. So the studies that I've seen increase one of the markers of inflammatory tone, high sensitivity CRP, by about two to three X. It seems to make the hypothalamic pituitary adrenal access more rigid so that you can't kind of roll with the punches and wax and wane in terms of cortisol production, the way that you can off the birth control pill.
It can affect thyroid function. Anytime you take oral estrogen, it raises sex hormone binding globulin, and you've talked to other podcast guests about this, Kyle, I think, sex hormone binding globulin, I think of as a sponge that soaks up free estrogen and free testosterone. So when you go on the birth control bill, you raise your sex hormone binding globulin, it soaks up especially free testosterone, and for some women, it's not a big deal. They don't notice much of a difference. But then there's a phenotype, maybe related to CAG repeats on the androgen receptor, who are exquisitely sensitive to that decline in free testosterone.
So this then opens the portal of talking a little bit about testosterone in women. It's the most abundant, biologically the most abundant hormone in the female system. It is so important for women. It is essential to so many things, not just sex drive and muscle mass and seeing a response to resistance training, but also confidence in agency. And so those women who are so sensitive to their testosterone level, they've got this high sex hormone binding globulin, their testosterone declines. What they describe is vaginal dryness, maybe a decline in sex drive, but there's also this bigger issue related to confidence in agency, even risk taking from studies that we've done with MBA students that I think is a serious problem.
Maybe the most important out of all of these things is that it can shrink the clitoris by up to 20%, 20%. If I've got a woman that I think should not be on the birth control bill, maybe she's taking it for acne or she's taking it because her periods were a little painful, what I'm going to do is say, let's leverage these other ways of making your period less painful. Let's take the message of your painful periods and figure out, okay, is it your inflammatory tone? And we give you some visual oil and SPMs, maybe a little aspirin when you've got your period.
Like let's find some other ways to deal with it than to take the oral contraceptive, which you have not received informed consent about because it can trick your clit by up to 20%. Now that usually convinces most people to come off of it. The data that we have is limited. There's one woman who, Claudia, something, something, who looked at sex hormone binding globulin a year out from stopping the birth control pill, and it was still elevated. It wasn't as high as it was when they were on the pill, but it was still elevated. So your question about reversibility, I don't know if we know the answer to that.
What are your thoughts on menopause? When should people start thinking about it? And I'm guessing based on everything you've told me today that there are women in their 30s that while they may be 20 years out from menopause, probably should be doing things now in anticipation of that. The more you know about your phenotype, your hormonal phenotype when you're in your 30s, you're set up in terms of what to do in the future, especially things like your thyroid, your estrogen and progesterone levels, because you can replace to a state of youth thyroid. I don't usually go exactly back to where the estrogen and progesterone levels were, but we can get pretty close.
So in your 30s, having a base case, I think is really essential. What's more interesting is to talk about perimenopause. So perimenopause is the period of time before your final menstrual cycle. And for most women, depending on how attuned you are to the symptoms, it can last for 10 years. So I'm still in perimenopause. It's been like 20 years because I've been tracking it so carefully. It usually gets kicked off by having your cycle get closer together. So that can happen in your 30s or your 40s. You go from 28 days to 25 days, that sort of thing. You may notice it as more anxiety, difficulty sleeping, and that probably is related to the estrogen receptor.
So there's this whole period of perimenopause, and what's most fascinating to me is that there is this massive, massive change that happens in the female brain that people are not talking about enough. And so looking at the work of Lisa Moscone at Cornell, starting around age 40. There is this massive change in cerebral metabolism. So you can do FDG PET scans, you can look at glucose uptake, and there's about on average a 20% decline from pre-menopause up to like age 35 to perimenopause to post-menopause. The women who are having the most symptoms in perimenopause to menopause, the hot flashes, the night sweats, the difficulties sleeping, those are the ones who have the most significant cerebral hypometabolism.
So it's almost like a, I don't want to scare people with this language, but it's a low level or let's call it pseudo dementia of sorts. Yes, it seems to be a phenotype that you can then map to Alzheimer's disease because that's Lisa Moscone's work. She's looking at, okay, Alzheimer's disease is not a disease of old age, it is disease of middle age. What are some of the biomarkers that we can define that can tell you what your risk is? I've got a mother and a grandmother with Alzheimer's disease. You can believe I am all over this data. And insulin resistance and sensitivity, as we talked about it before, seems to be somewhere in there, which I think when that idea first surfaced, a few people were like, really?
But then of course, right? I mean, the brain is just incredibly metabolically demanding. In Oregon, you deprive neurons of fuel sources. Or you make them less sensitive to fuel sources. They start dying, they certainly start firing less. It makes perfect sense. And I think now it's, thanks to Lisa's work, work that you've done and talked about quite a lot is in your books and elsewhere, I think it's really highlighted for people that metabolism and metabolomics is going to be as important as genes and genomics when it comes to dementia, perhaps, especially in women. Is it safe to say that? I think so because we believe that the system is regulated by estrogen.
So the decline in estrogen starting around age 40, 43 is kind of the average, seems to be the driver behind cerebral hypometabolism. The way I describe it to my patients is it's like slow brain energy. So you walk into a room, you can't remember why, like you just notice that you can't manage all the tasks the way that you once could. Like things are just a little slower. And I say that to women and they're like, I have that like, help me. We've got all of these women that are marching toward potentially a greater risk of Alzheimer's disease. And they have this opportunity in their forties and their fifties to take hormone therapy and they may not be offered it because the typical conventional approach based on WHI is to say, unless you're having hot flashes and night sweats that are severe, I'm not going to give you hormone therapy. And I just want to call that out. I would say, no, that is not the way to approach it. The concept right now in conventional medicine is that hot flashes and night sweats are these nuisance symptoms that we will take care of temporarily. Doesn't matter that you're not sleeping anymore.
Turn down the temperature in your room. And that's not right because hot flashes and night Sweats are a biomarker of cardiometabolic disease. They are a biomarker of increased bone loss. They are a biomarker of changes in the brain. So many of these symptoms that occur in perimenopause are not driven by the ovaries, they are driven by the brain. I just want to say you've taught me a tremendous amount. The amount of knowledge that you shared is immense and is going to be very useful and actionable for women in particular. Can I just add one last thing? I shouldn't talk about it since we didn't get to the 40s and the 50s and those list of biomarkers.
If women went away with one thing today, it would be to do a coronary artery calcium score by age 45 and sooner if you've got premature heart disease. How is that taken? So it's a CT scan of the chest. You can self-order it. It almost gives you this fork in the road in terms of how much you need to pay attention to cardiometabolic health as a woman. It's so fascinating because, you know, there's some women who have a zero, so my score is zero. But if you're 45 and you're starting to be elevated or you've got, you know, maybe you've got PCOS or you've got some other biomarkers tending you in this direction toward the number one killer, that allows you to really start to make changes. And I think it's essential to know that data. Most conventional doctors are not going to do it.
So if I were to go to my doctor and I just say I want a cardiac calcium score, That's what people should know. Coronary artery calcium score, CAC. Okay. There are certain people, they are exceedingly rare, but you are one such person that when they speak, knowledge just comes out of them and it's incredibly useful and helpful knowledge. So thank you. Thank you.