1. Polycystic ovarian syndrome and hemoglobin levels: is there a link?
Tjod 2017
Mustafa Gazi UÇAR1, Rahime Merve Uçar2, Tolgay Tuyan İLHAN1, Ersin Çintosun1, Ali Ünlü3, Çetin ÇELİK1
Yard. Doç. Dr. Mustafa Gazi UÇAR
S.Ü. Selçuklu Tıp Fakültesi
Kadın Hastalıkları ve Doğum AD

2. The prevalence of PCOS 4–10 % of all women (1).
Context: PCOS is the most common gynecological endocrinopathies affecting reproductive-age women.
It is considered both a metabolic and a reproductive disorder owing to its association with obesity, endocrinopathy, hyperandrogenism, hypertension, dyslipidemia, and cardiovascular diseases
The prevalence of PCOS 4–10 % of all women (1).
1- Nehir Aytan A, Bastu E, Demiral I, Bulut H, Dogan M, Buyru F. Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome. Gynecol Endocrinol 2016; 7:1-5.

3. Objective: We sought to investigate the role of androgen excess and oligomenorrheic or amenorrheic menstrual cycles, two major diagnostic criteria of PCOS, and their effect on hemoglobin concentrations.

4. Design: Prospective, cross-sectional study.
Subjects and Methods: This study included 82 PCOS (based on Rotterdam's criteria) and 69 non-PCOS women 20–25 years of age who attended to our obstetrics and gynecology outpatient clinic, between January and June 2016.

5. Diagnostic criteria for PCOS
The diagnosis of PCOS was based on a combination of clinical observations, in vitro analyses, and imaging tests in accordance with the 2003 Rotterdam classification, in which any two of the following three conditions need to be fulfilled for positive diagnosis:
1. Oligo- and/or anovulation, defined as fewer than nine menses per year or menstrual cycles longer than 35 days in length
2. Clinical hyperandrogenism (i.e., acne or hirsutism; modified Ferriman–Gallwey scores ≥8) or biochemical hyperandrogenism (i.e., free testosterone (FT) ≥7.0 pg/mL)
3. Polycystic morphology of the ovaries on ultrasound (presence in one ovary of ≥12 antral follicles measuring 2– 9 mm in diameter)
In addition to these criteria, a positive diagnosis of PCOS requires the exclusion of all other etiologies, including congenital adrenal hyperplasia, Cushing’s syndrome, and androgen-secreting tumors, which can result in menstrual irregularity and hyperandrogenism.

6. The control group consisted of healthy women undergoing routine checkups who had regular menstrual cycles and no report of other problems.
All participants underwent a medical history, physical examination, hematologic assessment, and biochemical tests.
PCOS patients were compared with non-PCOS controls in terms of hemoglobin levels and the prevalence of anemia.

7. The laboratory evaluations for women with suspected PCOS consisted of a
Complete blood count (CBC),
Thyroid function tests,
Serum prolactin levels,
A free-androgen index (calculated as total testosterone divided by sex hormone binding globulin [SHBG] × 100).

8. Anemia was diagnosed based on the standards set forth by the US Centers for Disease Control and Prevention (CDC) as hemoglobin concentration below the cutoff of <12.0 g/dL for women aged 15 years or older (2).
These results were compared with healthy controls with regular menstrual cycles.
2- Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep 1998; 47:1-29.

9. Results: No differences in age, socioeconomic status, or education level were identified between groups.
Mean hemoglobin concentrations in the PCOS and control groups were 13.2 ± 0.9 (9.4–15.1) and 12.8 ± 1.0 (9.6–14.8) g/dL, respectively.
The prevalence of anemia was lower among PCOS patients (8.5%) relative to controls (17%), with mean hemoglobin concentrations significantly higher in PCOS patients (p = 0.015).

10. Excessive production and secretion of androgens by steroidogenic tissues is the primary pathogenic mechanism in PCOS (3)
This form of androgen excess is typically characterized by clinical pathologies including hirsutism, acne, and androgenic alopecia, and is a central diagnostic criterion for PCOS.
3- Luque-Ramírez M, Escobar-Morreale HF. Targets to treat androgen excess in polycystic ovary syndrome. Expert Opin Ther Targets 2015; 19:

11. increased production of erythropoietin,
Androgens act on the hematopoietic system through a variety mechanisms including.
increased production of erythropoietin,
stimulation of bone marrow activity, and
increased incorporation of iron into red cells (4).
Accordingly, androgen therapy is now widely used to improve cytopenias associated with Fanconi anemia, particularly in patients who are unable to undergo or defer hematopoietic stem cell transplantation (5).
4- Shahani S, Braga-Basaria M, Maggio M, Basaria S. Androgens and erythropoiesis: past and present. J Endocrinol Invest 2009; 32:
5- Çetin M, Ünal Ş, Gümrük F, Gürgey A, Altay Ç. Serum Erythropoietin Levels in Pediatric Hematologic Disorders and Impact of Recombinant Human Erythropoietin Use. Turk J Haematol 2009; 5; 26:72-6.

12. The long phylogenetic history of these systems suggests that similar sex-related differences in hemoglobin levels are found not only in humans but also in many other vertebrate species (6).
6- Murphy WG. The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences. Blood Rev 2014; 28: 41-7.

13. Heavy, extended, or irregular menstruations may represent independent risk factors for anemia (7), on top of the broader risk of anemia in women of reproductive age as a result of blood loss, and therefore iron loss, associated with normal menstruation (8).
[7] Avci ME, Sadik S, Uçar MG. A prospective study of rollerball endometrial ablation in the management of refractory recurrent symptomatic endometrial hyperplasia without atypia. Gynecol Obstet Invest 2012; 74:
[8] Blanco-Rojo R, Toxqui L, López-Parra AM, et al. Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age. Int J Mol Sci. 2014; 15(3):

14. Several studies have shown that serum ferritin and anemia are correlated with both the duration of menstruation and extent of bleeding (9).
On average, females lose between 20 and 35 mL of blood per month, which equates to 11 mg of iron (10).
9- Heath AL, Skeaff CM, Williams S, Gibson RS. The role of blood loss and diet in the aetiology of mild iron deficiency in premenopausal adult New Zealand women. Public Health Nutr 2001; 4:
10- Janssen C, Scholten P, Heintz A. Reconsidering menorrhagia in gynecological practice is a 30-year-old definition still valid? Eur J Obstet Gynaecol Reprod Biol 1998; 78: 69–72.

16. Conclusion: Oligomenorrheic or amenorrheic menstrual cycles and androgen excess, two major diagnostic criteria of PCOS, may affect hemoglobin concentrations.
The data presented here show that women with PCOS had significantly higher levels of hemoglobin and lower rate of anemia compared to healthy controls.

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