CYP19A1, also known as aromatase, is an important enzyme that produces estrogen. By regulating estrogen levels, CYP19A1 affects a variety of processes in the body, including fat production and distribution, bone density, female fertility, and brain function. Estrogen deficiency is associated with diseases such as osteoporosis, hardening of the arteries, and Alzheimer’s. Furthermore, CYP19A1 gene variants are associated with migraines and the growth of estrogen-sensitive cancers. In this post, you will find information about aromatase function, gene variants, and natural substances that decrease its activity.

What is CYP19A1?

Aromatase (CYP19A1) is one of the cytochrome P450 monooxygenases (CYPs) [1].

Many CYPs eliminate toxins and drugs from the human body. However, some, like CYP19A1, are not involved in detoxification but in steroid hormone production.

Read more about CYPs here.

Function

Aromatase is a key enzyme in estrogen production. It converts androstenedione and testosterone to estrone and estradiol, respectively [2].

Location

This enzyme is found in the ovaries, placenta, testis, fat tissue, brain, liver, muscles, and hair follicles [3, 4, 5].

The Good

By regulating estrogen production, CYP19A1 affects a variety of processes in the body, such as fat production and distribution [6], bone density [7], female fertility [8], and brain function [9].

Estrogen deficiency is associated with a variety of diseases, including osteoporosis, hardening of the arteries (atherosclerosis), and Alzheimer’s disease [10].

CYP19A1 is also involved in the sexual development of the brain [9]. How the brain develops and functions depends on the levels of sex hormones it is exposed to.

Furthermore, CYP19A1 also affects cognitive function. It is implicated in reading, speech, and language [9]. Estrogen has important roles in learning and memory by enhancing neuron structure and function [9].

Mutations in CYP19A1 are associated with dyslexia (3423 subjects) [9].

Finally, a 38% reduction in CYP19A1 function was observed in patients with autism spectrum disorder (26 subjects) [11].

The Bad

Increased aromatase activity, resulting in higher estrogen, promotes the growth of estrogen-sensitive cancers.

Gene Polymorphism

To date, hundreds of CYP19A1 variants have been identified [12].

However, complete CYP19A1 enzyme deficiency is very rare. To date, only 24 cases have been reported worldwide [9, 13].

Clinical features of CYP19A1 deficiency include:

  • maternal virilization in pregnancy (male-pattern hair growth and other masculine physical traits) due to the excess of androgens and lack of estrogens coming from the fetus. These resolve gradually after giving birth [13].
  • (in women) virilized external genitalia, hemorrhagic ovarian cysts in childhood, primary amenorrhea (absence of menstruation), no breast development, and decreased bone density [13].
  • (in men) osteoporosis due to impaired bone mineralization. They also may have abnormal testis size and sperm production, metabolic syndrome-like stomach obesity, and insulin resistance [13].
  • RS10046

Having rs10046 (T) increases CYP19A1 levels (resulting in more estrogen) [5].

T/T contributes to hypertension (elevated blood pressure) (2250 and 443 subjects) [6, 14].

Having T/T also increases migraine susceptibility (283 subjects) [15].

On the other hand, C/C is associated with higher apo B, insulin, BMI, and HOMA index (2250 subjects) [6].

Patients with C may also be more prone to heart disease (189 subjects) [16].

  • RS1004982

rs1004982 C/C increases the risk of breast cancer (1958 subjects) [17].

  • RS1004984

rs1902584 A carrier women have a higher waist-to-hip ratio (they are more prone to obesity) (1241 subjects) [18].

  • RS17703883

C carriers among men (those with either T/C or C/C) have a 1.5 times higher risk of having a low bone mineral density (2392 subjects) [7].

  • RS1902584

rs1902584 T carrier women have a higher waist-to-hip ratio (they are more prone to obesity) (1241 subjects) [18].

  • RS2470144

Having rs2470144 A/A reduces the risk of rectal cancer (791 cases and 999 controls) [19].

  • RS28566535

Women with rs28566535 C/C have an increased breast cancer risk (1958 subjects) [17].

  • RS2899470

T carriers have a higher risk of endometriosis (262 patients and 275 controls) [20].

  • RS4646

The common rs4646 C variant increases estrogen levels and may predispose women to female pattern hair loss (955 subjects) [21].

On the other hand, the T variant for the rs4646 was associated with advanced stage of breast cancer at the time of presentation and a more progressive disease (327 patients) [22].

  • RS4775936

Woman A/A carriers have a higher bone mineral density (256 subjects) [23].

Having rs4775936 G/G increases the risk of breast cancer (1958 subjects) [17].

Also, blood pressure was higher in men but lower in women with the G/G (218 patients and 225 controls) [14].

Women A carriers had a greater risk of having higher blood pressure (639 subjects) [24].

  • RS700519

This variant was associated with endometrial cancer risk in postmenopausal women (1,040 patients and 1,031 controls) [2, 25].

Patients with rs700519 T/T had lower breast cancer survival (1,136 patients) [26].

  • RS727479

The C variant produces 10–20% more estrogen in postmenopausal women [27].

rs727479 C may increase the risk of lung cancer (529 patients and 567 controls) [28].

Carrying an A, on the other hand, increases the risk of endometrial cancer (10 studies, 4,998 cases, and 8,285 controls) [29].

  • RS749292

rs749292 produces 10-20% more estrogen in postmenopausal women [27].

The A variant increases the risk of endometrial cancer (10 studies, 4,998 cases, and 8,285 controls) [29] and ovarian cancer (367 cases and 602 controls) [27].

  • RS936306

Women with rs936306 T/T may have an increased risk of breast cancer (1958 subjects) [17].

  • RS700158

rs700158 G variant is a risk factor for preeclampsia (a pregnancy complication) (286) [30].

  • RS11632903 and RS1902586

rs11632903 and rs1902586 are moderately associated with dyslexia (3423 subjects) [9].

  • RS3751592

G in rs3751592 was associated with the incidence of Alzheimer’s disease (463 subjects) [12].

  • RS11575899

This variant (del/del) was significantly associated with melanoma (117 cases and 116 controls) [31].

Increasing or Decreasing CYP19A1

These increase CYP19A1:

  • Aflatoxin B1 [32]
  • Dichlorodiphenyl ethylene (DDE, derived from DDT) [33]

These decrease CYP19A1:

  • Olive tree leaves [34] and olive oil [35]
  • Curcumin [36]
  • Apigenin [37]
  • Naringenin [37]
  • Hesperetin [37]
  • Chrysin [38]
  • Kaempferol [39]
  • Capsaicin [40]
  • Mango peel [34]
  • Lemons and limonoids found in lemons [41]
  • Mangosteen [42]
  • Ginkgo biloba [43, 44]
  • Sumac sorghum bran extract [45]
  • Licorice flavonoid isoliquiritigenin [46, 47]
  • Biochanin A, from red clover (Trifolium pratense) [48]
  • Hop flavonoids xanthohumol, isoxanthohumol, and 8-prenylnaringenin [49, 50]
  • Lager beer, alcohol-free beer, stout beer, and xanthohumol-rich stout beer [50]
  • Red wine [38, 42]
  • Resveratrol [47]
  • Grape seed extract [51, 42]
  • Tea [38, 42]
  • Coffee [42]
  • Cocoa [42]
  • Collards (including cabbage and broccoli) [42]
  • Tomato leaves [42]
  • Stinging nettle root extract [52]
  • Cigarette smoke and tobacco leaves [42]
  • White button mushroom unsaturated fatty acids [53]
  • Damiana (Turnera diffusa) [54]
  • Piper cubeba [55], a type of pepper
  • Mammea siamensis [56]
  • Nelumal A, found in Ligularia nelumbifolia [57]
  • Rhus verniciflua [58]

These can both increase and decrease CYP19A1:

About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PhD (Ecological Genetics)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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