Hypogonadism in females

Author: Dr Gavin Esson, Foundation trainee, NHS Lothian, Edinburgh, Scotland. DermNet NZ Editor-in-chief: Adjunct Assoc. Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. April 2019.

 


What is hypogonadism in females?

Hypogonadism in females describes the inadequate function of the ovaries with impaired production of germ cells (eggs) and sex hormones (oestrogen and progesterone).

  • Primary hypogonadism refers to a condition of the ovaries (primary ovarian insufficiency/ hypergonadotrophic hypogonadism).
  • Secondary hypogonadism refers to the failure of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism).

What causes hypogonadism in females?

Hypogonadism in females is due to disruption of any section of the hypothalamic-pituitary-ovarian axis pathway (figure 1).

  • The hypothalamus produces gonadotrophin-releasing hormone (GnRH) at the onset of puberty.
  • GnRH then acts on the pituitary gland, which produced follicle-stimulating hormone (FSH) and luteinising hormone (LH).
  • FSH and LH then act on the ovaries to stimulate the production of oestrogen and progesterone.
Figure 1. The hypothalamic–pituitary–gonadal axis pathway

Who gets hypogonadism?

Primary ovarian insufficiency and secondary hypogonadism may be congenital or acquired [1,2].

Congenital primary ovarian insufficiency

The main mechanism for congenital primary ovarian deficiency remains unknown in the majority of cases. Some cases relate to:

Acquired primary ovarian insufficiency

The causes of acquired primary ovarian insufficiency include:

Congenital secondary hypogonadism

Congenital secondary hypogonadism is gonadotrophin deficiency due to genetic mutation, such as Kallmann syndrome.

Acquired secondary hypogonadism

Acquired secondary hypogonadism can be due to damage to the pituitary/hypothalamus. Examples may include:

  • Intracranial space-occupying lesion (eg, tumour, cyst)
  • Infiltrative disease (eg, sarcoidosis, haemochromatosis)
  • Infection (eg, meningitis, TB)
  • Pituitary apoplexy (bleeding into pituitary gland)
  • Trauma.

Gonadotrophins can be suppressed by:

  • Chronic disease (eg, diabetes, anorexia, obesity, renal disease)
  • Excessive exercise
  • Critical illness
  • Chronic opiate, glucocorticoid or anabolic steroid use
  • Hyperprolactinaemia.

What are the clinical features of hypogonadism in females?

The clinical features of hypogonadism depend on the age at presentation [3].

Oestrogen deficiency pre-puberty

Symptoms of low oestrogen levels are rarely present in hypogonadism pre-puberty. The presenting features are absent pubertal development (reduced growth and absence of pubic hair) and primary amenorrhoea (absence of menarche).

Oestrogen deficiency after completion of puberty

After the completion of puberty, the features of hypogonadism include:

  • Secondary amenorrhoea (cessation of regular menses for three months or the cessation of irregular menses for six months)
  • Symptoms of the climacteric (peri-menopause): palpitations, heat intolerance, flushing, night sweats, irritability, anxiety, depression, sleep disturbance, loss of libido, coarse hair, vaginal dryness, fatigue
  • Infertility.

What are the complications of oestrogen deficiency?

The long term risks of oestrogen deficiency include an increased risk of osteoporosis and cardiovascular disease. The risk is greater with a younger age of onset. In contrast, the risk of breast cancer may be slightly reduced.

What skin changes may be due to hypogonadism in females?

Oestrogen has a key role in maintaining skin health. Oestrogen helps maintain skin thickness and collagen levels, skin elasticity, and moisture. It is also thought to play a role in wound healing [4].

Low oestrogen levels are associated with:

  • Dry, thin skin
  • Potentially increased wrinkles
  • Delayed wound healing
  • Loss of elasticity, thickness and moisture of vulval skin, resulting in genitourinary discomfort.

Skin changes may also reflect the underlying cause of hypogonadism, for example, hyperpigmentation may be a sign of an autoimmune disease.

How is hypogonadism diagnosed?

If hypogonadism is suspected following a detailed history and examination, the following investigation pathway can be followed. The patient should be referred to a specialist.

Initial investigations should include [5,6]:

  • hCG (exclude pregnancy)
  • FSH and LH
  • Oestradiol
  • TSH (thyroid disorders can present with amenorrhoea)
  • Serum prolactin
  • Pelvic ultrasound scan (pre-puberty).

Interpretation of the results

  • A positive hCG is due to pregnancy.
  • If the uterus is absent or there are other anatomical anomalies, a karyotype should be performed.
  • Low or low/normal FSH and LH may indicate hypogonadotropic hypogonadism. An MRI brain should be considered.
  • Pre-puberty, high FSH and LSH may indicate primary ovarian insufficiency. Adrenal hormones should be assessed and a karyotype should be performed.
  • A raised prolactin should prompt consideration of a pituitary MRI.

What is the treatment for hypogonadism in females?

Treatment of hypogonadism is directed at the underlying pathology where possible, helping the woman become fertile if desired, and preventing the long-term complications of hypoestrogenism (osteoporosis, increased cardiovascular disease, urogenital atrophy).

As a general rule, women of reproductive age with hypoestrogenism should receive hormone replacement therapy. Specialist input should be sought, as there are potential significant complications of hormone therapy, such as;

  • Endometrial hyperplasia and carcinoma in unopposed oestrogen therapy; it is usual to add a progestin to stop this
  • Increased risk of breast cancer, venous thromboembolism, stroke, ischaemic heart disease.

Post-menopause, hormone replacement therapy is indicated for significant symptoms.

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Related information

 

References

  1. Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency - an update on recent advances in understanding and management. F1000Research. 2017, 6:2069. PubMed.
  2. Silveira LF, Latronico AC. Approach to the patient with hypogonadotrophic hypogonadism. J Clin Endocrinl Metab. 2013, 98(5):1781-8. PubMed.
  3. Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis. 2006. 6;1:9. PubMed Central.
  4. Shu YY, Maibach HI. Estrogen and the skin - therapeutic options. Am J Clin Dermatol. 2011, 12(5):297-311. PubMed.
  5. Welt CK, Barbieri R. Evaluation and management of primary amenorrhoea. UpToDate. 2018. Accessed February 2018.
  6. Welt CK, Barbiere R. Evaluation and management of secondary amenorrhoea. UpToDate. 2018. Accessed February 2018.

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