Polycystic Ovary Syndrome

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Classification according to ICD-10
E28.2 Polycystic Ovarian Syndrome
ICD-10 online (WHO version 2019)

The polycystic ovary (or ovarian ) syndrome ( English polycystic ovary syndrome ; in short, polycystic ovary syndrome , PCOS ), actually syndrome poly cystic ovaries , short and polycystic ovaries , is one of the most common metabolic disorders of mature women , triggered by different pathogenetic mechanisms and characterized by a complex disrupted hormonal balance. PCOS is the most common cause of increased androgen levels ( hyperandrogenemia ), menstrual disorders (failure of ovulation ) and infertility in women. The older name Stein-Leventhal syndrome is still in use today. Other possible names are chronic hyperandrogenemic anovulation ( CHA ) or polycystic ovarian disease ( PCOD ).

Occurrence

PCO syndrome affects an estimated four to twelve percent of women of childbearing age in Europe . This makes it the most common hormonal disorder in women of this age group and the most common cause of infertility due to menstrual disorders. Overweight women seem to be affected significantly more often. With the increasing prevalence of obesity , a further spread of the disease is expected. But even slim women with a normal BMI are about five percent affected and show no insulin resistance . In addition, the polycystic ovary syndrome is often associated with thyroid diseases .

Definition and clinical symptoms

According to the definition of the conference of the " European Society of Human Reproduction and Embryology " (ESHRE) and the " American Society for Reproductive Medicine " (ASRM), which was presented in Rotterdam in 2003, a PCO syndrome is present if two of the three following criteria are met are fulfilled:

Polycystic ovary on the sonogram

Proof of the eponymous polycystic ovaries is therefore not necessary for the diagnosis of "PCOS". On the other hand, if polycystic ovaries are detected, PCOS is not always present: Polycystic ovaries can be found in up to 23 percent of all women with a normal cycle.

Another symptom of this syndrome is weight gain (see below).

Laboratory diagnostics

Laboratory diagnostics can result in:

causes

The pathogenesis of polycystic ovary syndrome is not yet fully understood.

Using special mouse models, however, it has been shown that a hormonal imbalance in the womb during embryonic development could be the cause of the disease. Pregnant mice were injected with excessive doses of the so-called anti-Müllerian hormone and, as a result, an increased incidence of the disease in the newborn mice was observed. The high AMH levels lead via corresponding signal cascades to a stimulation of certain brain areas, which upregulate the production of testosterone. As a result, these mice also had the increased AMH level characteristic of the PCO syndrome. This also explains the familial accumulation of the disease, as the disease maintains itself via this mechanism and transfers it to the next generation. The researchers were also able to reverse this effect with the help of a drug that had been used for a long time in reproductive medicine, albeit with a different intention. They gave the mice born under AMH overexposure a GnRH antagonist, namely cetrorelix, which stopped the symptoms.

In the area of ​​molecular biology, too, recent progress has been made towards a more precise explanation of the cellular processes of the disease. A large number of genetic signals could be identified, the influence of which on the appearance of the polycystic ovary syndrome could be proven, mainly the EGF receptor and the FSHB locus. Future causal treatment options for polycystic ovary syndrome are promised in this article. Special attention is etiologically the aforementioned EGF receptor and the pituitary gonadotropins , the body mass index , the higher insulin resistance and SHBG . Furthermore, the alleles which a susceptibility represent for polycystic ovary syndrome, all with the serum - AMH - concentration associated.

Increased serum concentrations of LH with simultaneous normal FSH can be detected in many, if not all cases. A hyaline thickening of the basal lamina presumably leads to an FSH resistance of the granulosa cells of the ovary. In response to the FSH-related reduced aromatase activity , there is a permanent stimulation of the LH secretion, which in turn leads to a derailment of androgen production . Disturbances of the neurotransmitter and opiate metabolism as well as a hyperandrogenemia- associated disturbance of the release of the hypothalamic gonadotropin-releasing hormone ( GnRH ) are discussed as further backgrounds .

Since the realization that insulin is able to stimulate ovarian androgen production, insulin resistance with subsequent hyperinsulinemia (excessive insulin production) has become increasingly important in the pathogenesis of PCOS. Hyperinsulinemia also increases the proportion of free testosterone by reducing the synthesis of sex hormone-binding globulin (SHBG) in the liver and thus increases the effect on the androgen receptor.

Hyperinsulinemia and elevated LH are now considered to be the dominant factors in the development and maintenance of PCOS.

Insulin resistance almost always found in severely obese (obese) women, making this a special PCOS- disposition have. It is estimated that more than 50 percent of PCOS patients are overweight. In the puberty is obesity , the most common cause for the development of PCOS. For slim women without insulin resistance, there is currently no cause research or explanation. However, the latest research from Israel has shown that slim women with polycystic ovary syndrome without insulin resistance experience an improvement in their hormonal situation if they eat most of their food in the morning.

With increased testosterone, muscle fiber type I (pronounced capillarization , high levels of insulin receptors) changes to muscle fiber type II (reduced capillarization, low levels of insulin receptors) in the female body . As a result, less glucose is consumed and there is increased fat storage in the abdominal area . This creates a kind of “ vicious circle ” in which the hyperinsulinemia maintains the increased androgen production of the ovaries and the increased androgens in turn maintain the insulin resistance.

In addition, a primary hyperandrogenemia can also induce an increase in the muscle fiber type II / type I ratio. The subsequent insulin resistance and hyperinsulinemia are followed by the development of PCOS. This explains the frequent coincidence of a 21-hydroxylase deficiency of the “late-onset” AGS with polycystic ovaries; however, exogenous hyperandrogenemia, for example due to anabolic steroids , are also possible.

Due to the importance of insulin resistance and obesity for the development of PCOS, it is assumed that a considerable proportion of the PCOS cases that occur today are lifestyle-related. Even a possibly genetic disposition to insulin resistance should not be interpreted as fundamentally disease-related . Rather, it is probably an evolutionary development for times with limited food supply, which only becomes a health risk in our time, when there is an unlimited supply of high-glycemic , high- energy foods with, at the same time, often only low physical stress with a correspondingly reduced need for calories .

Possible consequences and complications

therapy

If a polycystic ovary syndrome is associated with overweight , the first therapeutic approach is to prevent obesity , especially adolescence with the following excessive insulin resistance . Appropriate diet and physical activity can make valuable contributions to this. The importance of diet and lifestyle in slim women with PCOS remains questionable. The study by the Israeli researchers suggests that food intake mainly in the morning led to an improvement in the hormonal situation and ovulation in 50% of women. It makes therapeutic sense to limit the development of PCOS-typical dysregulations as much as possible. In order to treat an already established PCOS, a distinction must be made as to whether or not a pregnancy is desired.

No desire to have children

If you do not wish to have children , you can treat with an antiandrogenic drug (active ingredient e.g. cyproterone acetate ), sometimes in combination with a birth control pill. This can lead to more regular bleeding and regulation of the hormonal balance of those affected. Androgenisation symptoms decrease.

Desire for children

If, on the other hand, the desire for pregnancy is paramount, the disease can be treated with the following drugs and forms of therapy, and if these fail, artificial insemination can be used.

Due to the chronic or progressive nature of many androgen balance disorders, one has to be prepared for long-term treatment. Therefore, after nine to twelve months at the latest, the success of the therapy should be objectified and, if necessary, a change in medication initiated.

PCOS and cycle irregularities

Many women with pronounced polycystic ovary syndrome have no or only an irregular cycle. Reasons for this can be the increased free testosterone and, in many cases, the increased anti- Müllerian hormone (AMH). The latter can arrest the cycle at a stage just before the selection and visible maturation of the leading follicle. As a result, so many relatively small follicles can mature in both ovaries and produce the familiar ultrasound morphological picture of the cystic ovaries. Therapy with metformin or, in the event of intolerance to insulin sensitizers ( glitazones ) in sufficient doses, can be expected to reduce the anti-Müllerian hormone serum level significantly over a period of around four to five months in the medium to long term. The therapeutic supportive measures mentioned in the section above should be observed in parallel. As a result, in the ideal case, stable, normal levels of the classic cycle hormones can be detected in the corresponding laboratory tests, as well as a spontaneous menstrual cycle, which then paves the way for spontaneous pregnancies.

The background to the effect on the cycle of the anti-Müllerian hormone, which is usually up to three times higher in PCOS women, is that the high AMH concentration strongly inhibits the aromatase of the granulosa cells of the ovary. The aromatase is normally responsible for enabling the follicles to form estrogen , which initiates the formation of the leading follicle during the menstrual cycle by making it independent of the stimulation hormone FSH . Without sufficient estrogen production, the cycle gets stuck at this point, which leads to the ultrasound image of many small, long-lived "cysts" in both ovaries, which is part of the disease definition.

The excessively increased AMH levels themselves are in turn caused by the early contact of the primordial follicles of the ovary with excessively high insulin concentrations, as the production of AMH in the affected follicles is permanently upregulated by the high-dose insulin effect. Under the insulin-lowering measures as described above this damage is minimized. However, a complete cohort maturation cycle, which usually lasts approx. 4 months, usually has to be carried out before the effect of the therapy becomes clinically apparent, since only then are all the damaged follicles still present completely consumed. It should therefore be ensured that the cycle duration is kept as short as possible during this time. This can be achieved through regular, timely pill or progestogen intake to induce menstruation. Those unresponsive to or intolerant of the above for the implementation cycle normalization steps necessary drugs and fertility are more reproductive medicine embossed approaches, mainly carried out in fertility clinics , are available.

The measurement of the AMH level in the blood can also be used as an effective prognostic marker for therapy with metformin.

acupuncture

The effectiveness of acupuncture on PCOS is debatable. In 2007, Swedish authors came to the conclusion that acupuncture by modulating the neuroendocrine system (especially the sympathetic nervous system) has a positive effect on PCOS and can have a long-lasting positive effect on the metabolism and endocrine system as well as on ovulation . Chinese authors made it clear in 2008 that the current study situation is insufficient to confirm the ovulation-promoting effect of acupuncture with regard to PCOS.

See also

literature

  • Schöfl, Schill, Geisthövel, Brabant: Polycystic Ovarian Syndrome and Insulin Resistance. In: Dtsch Arztebl 2004. 101, pp. A 346–351 (issue 6). Full text
  • Urdl: The treatment of metabolic abnormalities in women with polycystic ovary syndrome. In: Journal für Fertilität und Reproduktion 2002. 12 (1) (edition for Austria), pp. 17–22. Full text (PDF; 1.3 MB)
  • Groll, Jeremy, MD and Lorie: Fertility Foods - Optimize Ovulation and Conception Through Food Choices. Simon & Schusters, New York 2006.
  • Keck: Fertility treatment in the gynecological practice: Sensible diagnostics ... , Thieme Verlag 2014
  • Gautam Allahbadia, Rina Agrawal, Rubina Merchant: Polycystic Ovary Syndrome , Anshan 2007 (English)

Individual evidence

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  2. ^ Robert J. Norman, Didier Dewailly, Richard S. Legro, Theresa E. Hickey: Seminar: Polycystic ovary syndrome In: The Lancet 2007; 370, pp. 685-697 abstract
  3. ^ Tommaso Falcone: Androgen Response to Endogenous Insulin Secretion during the Frequently Sampled Intravenous Glucose Tolerance Test in Normal and Hyperandrogenic Women. . In: The Journal of Clinical Endocrinology & Metabolism . December 1, 1990. doi : 10.1210 / jcem-71-6-1653 .
  4. Paolo Giacobini: Elevated prenatal anti-Müllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. . In: Nature . May 14, 2018. doi : 10.1038 / s41591-018-0035-5 .
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  13. ^ NF Goodman et al .: American Association of Clinical Endicronologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the best practices in the evaluation and treatment of Polycistic ovary syndrome - Part 2. In: Endocr Pract. tape 21 , December 21, 2015, p. 1415-1426 , doi : 10.4158 / EP15748.DSCPT2 , PMID 26642102 .
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  19. D. Menichini, F. Facchinetti: Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review . In: Gynecological Endocrinology: the Official Journal of the International Society of Gynecological Endocrinology . tape 36 , no. 1 , January 2020, p. 1–5 , doi : 10.1080 / 09513590.2019.1625881 , PMID 31187648 .
  20. Miao CY, Fang XJ, Chen Y, Zhang Q: Effect of vitamin D supplementation on polycystic ovary syndrome: A meta-analysis . In: Experimental and Therapeutic Medicine . tape 19 , no. 4 , April 2020, p. 2641–2649 , doi : 10.3892 / etm.2020.8525 , PMID 32256745 , PMC 7086222 (free full text).
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  23. Rebeccah Shalev, ND, Factoria Women and Family Clinic in Bellevue, WA: Spearmint for PCOS: A safe and effective treatment for hirsutism. In: Botanical Medicine, Endocrinology. Nature Cure, Women's Health, December 2, 2015, accessed August 31, 2018 .
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