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October 13, 2021

Menopause Part 5: Laboratory Evaluation

Welcome to part 5 of the ODX Menopause Series. In this post, the ODX Research team addresses general and specific blood chemistry changes that occur during the transition from premenopause to postmenopause. 

The ODX Menopause Series

  1. Menopause Part 1: A Quick Overview of a Slow Process
  2. Menopause Part 2: Biology and Physiology of Menopause
  3. Menopause Part 3: Increased Risk of Disease Associated with Menopause
  4. Menopause Part 4: Identifying Menopause: Signs and Symptoms
  5. Menopause Part 5: Laboratory Evaluation of Menopause
  6. Menopause Part 6: Cardiovascular Risk in Menopause
  7. Menopause Part 7: Beyond Hormone Testing in Menopause
  8. Menopause Part 8: Natural Approaches to Menopause
  9. Menopause Part 9: Diet and Nutrition Intervention in Menopause
  10. Menopause Part 10: Characteristic of Herbal Derivatives used to Alleviate Menopause Symptoms
  11. Menopause Part 11: Lifestyle Approaches to Menopause
  12. Menopause Part 12: The National Institute on Aging Addresses Hot Flashes
  13. Menopause Part 13: Hormone Replacement Therapy (HRT) in Menopause
  14. Menopause Part 14: North American and European Guidelines for Hormonal Management of Menopause
  15. Menopause Part 15: Bioidentical Hormone Therapy
  16. Menopause Part 16: Optimal Takeaways for Menopause
  17. Optimal The Podcast - Episode 10

Research suggests that severity of some symptoms is associated with variability of hormone levels, not just general declines.[1] [2]

Hormonal fluctuations during the perimenopausal period cause irregular menstruation, hot flashes, sleep disruption, and changes to vaginal integrity. Laboratory testing can help confirm that these symptoms are related to menopausal changes, especially in women younger than 50 or those who have had a hysterectomy.[3]

For women with vasomotor symptoms whose menstruation has ceased for greater than one year, diagnosis of menopause can be fairly straightforward without the need for extensive laboratory investigation.[4]

However, the perimenopausal period is characterized by notable biomarker patterns that can be assessed. During the transition from pre- to postmenopause, serum levels of estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) decrease while levels of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) increase.[5] Progesterone will decline as well.[6]    

These changes have biochemical causes and effects:[7]

  • Serum estrogens and inhibins decrease as ovarian follicles are depleted.
  • Increases in pituitary gonadotrophins FSH and LH occur in the body’s attempt to stimulate ovulation.
  • Depletion of estrogen and progesterone contributes to other biochemical changes in the body as well.

Serum concentrations of DHEAS follow a unique pattern in menopausal women with levels declining with age until early menopause, with an increase between early and late menopause. After this period, levels of DHEAS begin to decline again.[8]

Other biochemical changes can be detected as well due to glucose intolerance, hyperinsulinemia, insulin resistance, and dyslipidemia that commonly occurs with menopause. These metabolic changes can progress to coronary and peripheral artery disease.[9]

Salivary and urine measurement of hormone metabolites may be employed during the assessment of menopause. However, such evaluation is outside the scope of this review.[10] [11]

Laboratory Changes Associated with Menopause [12] [13] [14] [15] [16]

Decreased

  • Adiponectin
  • AMH
  • Estradiol
  • Ghrelin
  • HDL-cholesterol
  • Inhibin A and B
  • Progesterone

Increased

  • Apolipoprotein B
  • Cholesterol, total and LDL
  • FSH
  • Leptin
  • LH
  • Resistin
  • Triglycerides

Biochemical Phases of Menopause

Although not necessarily diagnostic, distinct changes in hormone levels can be observed during various phases of menopause:[17] [18]

Perimenopause

Early menopausal transition

    • Disturbed regulation of ovulation
    • Elevated FSH, low anti-mullerian hormone, low inhibin B, minor increase in LH
    • Progesterone and estradiol tend to be unaffected in this phase unless superimposed ovulatory LOOP cycles persist, leading to highly variable estradiol levels and low luteal phase progesterone.

Late menopausal transition

    • Paucity of ovulation
    • FSH above 25 IU/L, Low AMH (may be undetectable), low inhibin B
    • LDL and triglycerides can increase between early perimenopause and early postmenopause.

Early menopause

    • Elevated variable FSH, low AMH, low inhibin B
    • Bone mineral density loss is greatest the year before menstruation ceases and for two years after with annual losses of 1.8-2.3% in the lumbar spine and 1-1.4% in the hip. Bone loss was 35-55% greater in women in the lowest tertile of body weight.
    • Researchers suggest that bone loss in perimenopause may be due to elevated FSH, cortisol, and epinephrine instead of reductions in estradiol.

Menopause

  • Elevated stable FSH, very low AMH, very low inhibin B
  • Estrogen and progesterone are both low
  • Estrone higher than estradiol

Postmenopause

According to the Association for Clinical Biochemistry & Laboratory Medicine, the following serum hormone levels are characteristic of the postmenopausal period:[19]

Biomarker

Premenopausal

Postmenopausal

Anti-mullerian Hormone (AMH)

Greater than 2.8 ng/mL

20 pmol/L

 

Below 2.1 ng/mL

15 pmol/L

Estradiol

Depends on point in cycle

 

2.7-7.4 pg/mL  

9.8-27.1 pmol/L

FSH

10 IU/L

 

above 60 IU

Mean 100 IU/L

Inhibin A

25 ng/L

10 ng/L or less

Inhibin B    

50 ng/L

25 ng/L or less

LH            

Depends on point in cycle

10-45 IU/L

Testosterone, total

 

11.82-26.8 ng/dL

0.41-0.93 nmol/L

13.26-30.26 ng/dL

0.46-1.05 nmol/L

Testosterone, free

1.6-3.9 pg/mL

5.5-13.4 nmol/L  

  

1.5-4.2 pg/mL

5.4-14.7 pmol/L

The following reference intervals represent ranges for estradiol and progesterone used by commercial labs. As you can see values vary from timing of the blood draw but also vary from lab to lab. That is why it’s important to use the same laboratory to repeat and compare lab values.

Standard Reference Intervals

Quest Diagnostics[20] [21]

Labcorp[22] [23]

 

Serum     

Estradiol pg/mL

Female

  • Follicular Phase 19-144
  • Mid-Cycle            64-357
  • Luteal Phase       56-214 
  • Postmenopausal   ≤31

Male                   ≤39

Adult female:

  • Follicular: 12.5−166
  • Ovulation: 85.8−498
  • Luteal: 43.8−211
  • Postmenopausal: <6.0−54.7

Adult male 7.6−42.6

Serum Progesterone ng/mL

Adult Females

  • Pre-Menopausal
  • Mid Follicular ≤0.3
  • Pre-Menopausal
    Surge   0.1-1.5
  • Pre-Menopausal
    Mid Luteal       6.7-22.2
  • Postmenopausal Phase ≤0.2

 

Adult Males over 30                   ≤0.2

Female

  • Follicular phase 0.1−0.9
  • Luteal phase 1.8−23.9
  • Ovulatory phase 0.1−12.0
  • Postmenopausal 0.0−0.1

 

Male    0.0−0.5

References

[1] Joffe, Hadine et al. “Impact of Estradiol Variability and Progesterone on Mood in Perimenopausal Women With Depressive Symptoms.” The Journal of clinical endocrinology and metabolism vol. 105,3 (2020): e642–e650. doi:10.1210/clinem/dgz181

[2] Chiang, Catheryne et al. “Hormone variability and hot flash experience: Results from the midlife women's health study.” Maturitas vol. 119 (2019): 1-7. doi:10.1016/j.maturitas.2018.10.007

[3] Lab Tests Online Menopause Testing. Last reviewed April 30, 2021. Accessed July 18, 2021.

[4] Neves-E-Castro, Manuel et al. “EMAS position statement: The ten point guide to the integral management of menopausal health.” Maturitas vol. 81,1 (2015): 88-92. doi:10.1016/j.maturitas.2015.02.003

[5] Edlefsen, Kerstin L et al. “The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women.” Menopause (New York, N.Y.) vol. 17,3 (2010): 622-9. doi:10.1097/gme.0b013e3181cb49e9

[6] Kaya, Cihan et al. “The relation among steroid hormone levels, lipid profile and menopausal symptom severity.” Journal of psychosomatic obstetrics and gynaecology vol. 38,4 (2017): 284-291. doi:10.1080/0167482X.2017.1321633

[7] Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930

[8] Crawford, Sybil et al. “Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition.” The Journal of clinical endocrinology and metabolism vol. 94,8 (2009): 2945-51. doi:10.1210/jc.2009-0386

[9] Barańska, Agnieszka et al. “Effects of Soy Protein Containing of Isoflavones and Isoflavones Extract on Plasma Lipid Profile in Postmenopausal Women as a Potential Prevention Factor in Cardiovascular Diseases: Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Nutrients vol. 13,8 2531. 24 Jul. 2021, doi:10.3390/nu13082531 [R}

[10] Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930

[11] Newman, Mark, and Desmond A Curran. “Reliability of a dried urine test for comprehensive assessment of urine hormones and metabolites.” BMC chemistry vol. 15,1 18. 15 Mar. 2021, doi:10.1186/s13065-021-00744-3

[12] Barańska, Agnieszka et al. “Effects of Soy Protein Containing of Isoflavones and Isoflavones Extract on Plasma Lipid Profile in Postmenopausal Women as a Potential Prevention Factor in Cardiovascular Diseases: Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Nutrients vol. 13,8 2531. 24 Jul. 2021, doi:10.3390/nu13082531 [R}

[13] Ko, Seong-Hee, and Hyun-Sook Kim. “Menopause-Associated Lipid Metabolic Disorders and Foods Beneficial for Postmenopausal Women.” Nutrients vol. 12,1 202. 13 Jan. 2020, doi:10.3390/nu12010202

[14] Kruszyńska, Aleksandra, and Jadwiga Słowińska-Srzednicka. “Anti-Müllerian hormone (AMH) as a good predictor of time of menopause.” Przeglad menopauzalny = Menopause review vol. 16,2 (2017): 47-50. doi:10.5114/pm.2017.68591

[15] Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930

[16] Kaya, Cihan et al. “The relation among steroid hormone levels, lipid profile and menopausal symptom severity.” Journal of psychosomatic obstetrics and gynaecology vol. 38,4 (2017): 284-291. doi:10.1080/0167482X.2017.1321633

[17] Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930

[18] Hale, Georgina E et al. “The perimenopausal woman: endocrinology and management.” The Journal of steroid biochemistry and molecular biology vol. 142 (2014): 121-31. doi:10.1016/j.jsbmb.2013.08.015

[19] Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930

[20] Quest Diagnostics. Estradiol.

[21] Quest Diagnostics. Progesterone.

[22] Labcorp Estradiol.

[23] Labcorp Progesterone.

Tag(s): Biomarkers

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