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Hormonal causes of vulvodynia

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Andrew Goldstein

on 1 April 2018

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Transcript of Hormonal causes of vulvodynia

Anti-androgenic
effects of OCPs
Ovarian suppression of (total) testosterone production.
Increase production of SHBG.
This combination leads to a > 75% reduction in free (bioavailable) testosterone !!!!!!
Some progestins also act as androgen antagonists at the Androgen Receptor (AR) .
What are the consequences of these
anti-androgenic effects of OCPs?
Decreased arousal (FSAD). 1
Decreased libido (HSDD). 2
Decreased orgasm (FSOD). 3
Decreased frequency of intercourse. 3

1) McCoy NL, Matyas JR. Oral contraceptives and sexuality in
university women. Arch Sex Behav 1996;25:73–90.
2) Sanders SA, Graham CA, Bass JL, Bancroft J. A prospective
study of the effects of oral contraceptives on sexuality and
well-being and their relationship to discontinuation. Contraception
2001;64:51–8.
3) Battaglia C, Battaglia B, Mancini F, Busacchi P, Paganotto
MC, Morotti E, Venturoli S. Sexual behavior and oral contraception:
A pilot study. J Sex Med 2012;9:550–7.

Consequences of anti-androgenic
effects of OCPs

Only three months on Yasmin (EE 30mcg, Drosperinone 3mg) causes:
Decreased size of the clitoris (1)
Decreased thickness of the labia (1)
Decreased diameter of the introitus (1)
Increased pain with intercourse (1)
(3mg of Drosperinone is equivalent to only 25mg of spironolactone)

Decreased dermal papillae (2)
Decrease mechanical pain threshold (3)



1. Battaglia C, et al J Sex med 2012;9:550–7.
2. Johannesson U et al Br J Dermatol. 2007, 157: 487-493
3. Bohm-Starke N J Reprod Med. 2004 Nov;49(11):888-92.



24 year old woman presents with a complaint of 18 months of "knife-like" pain upon penetration.
Gradual onset of pain after 2 years of pain free intercourse.

OCPs and vestibulodynia?

Johannesson U et al Br J Dermatol. 2007, 157: 487-493)

Vestibular Epithelium of
Women on OCPs

Normal Vestibular
Epithelium

OCP Induced histologic changes

There is a loss of dermal papillae while on OCPs that increases the risk of mechanical strain (tearing, micro-fissures)
Treatment: Stop hormonal contraceptives then use: estradiol 0.01%/testosterone 0.1% BID to the vestibule. Expect no improvement for 6 weeks, 50% by 12 weeks.


Androgen receptor CAG repeats
Additional Concerns Regarding
OCPs and Sexual Function
50 consecutive women who had
secondary vestibulodynia that started while on OCPs
.
Pain
throughout the entire vestibule

No hypertonic pelvic floor muscle dysfunction.
Treatment consisted of stopping OCPs and application of estradiol 0.01% and testosterone 0.1% in a methylcellulose base applied BID for 3-6 months.
No additional treatments (TCAs, SNRIs, gabapentin, lidocaine, PT, diazepam, Botox, etc)
Do OCPs cause vestibulodynia?

The Embryology of the Vulva is Important
P=0.001
The vulvar vestibule is derived from the endoderm. It is the the embryological homolog of the male urethra.
Bartholin's glands, Skene's glands, and minor vestibular glands are the embryological homologs to the Cowper's glands, Prostate, and Gland's of Lettre.
So what are the implications of the embryology ?
The endothelium (mucosa) of the vestibule is androgen dependant.
The Bartholin's glands, the Skene's glands, and the minor vestibular glands are
ANDROGEN DEPENDANT, MUCIN-SECRETING GLANDS
Many studies have (mistakenly) focused on estrogen or the change in expression of the estrogen receptors not on androgen or the AR
THE SKENE'S GLANDS STAIN FOR PSA
But the MILLION DOLLAR question is which women get OCP induced vestibulodynia?
ANDROGEN RECEPTOR GENE
Located on the X chromosome at Xq11-12
Regulates androgen signaling in steroid hormone-sensitive cells
Highly polymorphic cytosine-adenine-guanine trinucleotide repeat
The CAG polymorphism may contain between 11-32 repeats
The length of the polymorphism is INVERSELY associated with androgen dependant gene transcription.
(DON'T FALL ASLEEP, THIS IS WHERE IT GETS REALLY INTERESTING)
So a woman with a short AR (fewer CAGs) is driving a Smart Car and woman with long AR (more CAGs) is driving a Hummer. If there is plenty of gas, both women do well.
BUT, if there is a gas shortage, the woman driving the hummer is going to run out of gas much, much sooner!
OCPS cause a gas shortage (low free testosterone) in EVERY WOMAN.


Study Group: 30 women who developed vestibulodynia while taking OCPs and whose vestibulodynia resolved after stopping OCPs and being treated with E/T gel (21/30 were taking a OCP containing drospirenone)
Controls 17 women currently taking OCPs containing drospirenone who have no evidence of vestibulodynia
Examined number of CAG repeats of the AR.
OUR STUDY
Results
Study group had mean number of biallelic CAG repeats 22.05 +/- 2.98 vs 20.61 +/- 2.19 for controls. p=0.025, d=0.53
When only the longer of the two CAG repeats (CAG-L) was examined (remember this gene is on the X chromosone) as would be expected if there was skewed x-inactivation then the mean allelic length was 23.73 +/- 2.59 for the study group and 21.76 +/- 2.11 for the controls P <0.05, d=0.53.
When the CAG-L of the study group was compared to a previously published database of 522 Caucasian women (CAG-L 22.4 +/- 2.5) the CAG-L for the study group was significantly longer P= 0.011
Interesting the mean duration of OCP use was 6.2 years for controls and 4.2 years for the study group. P= 0.02
In conclusin, it is clear that:
Spironolactone
a synthetic steroid that is an anti-androgen:
competitively binds to androgen receptor
inhibits 5alpha-reductase activity
reduces androgen biosynthesis.
No data on humans but...
Spironolactone changes pair-bonding in Prairie Vols!
Curtis, TJ, Wang, Z .
Neuroscience
. Volume 134, Issue 2, 2005, Pages 369–376
Even Scarier
Women choose different partners if they are using OCPs then if not using OCPs.
What about spironolactone?
Andrew T. Goldstein, MD, FACOG IF
Director, The Centers for Vulvovaginal Disorders
Past-President, The International Society for the Study of Women Sexual Health
obstetrics@yahoo.com, 410-279-0209

Hormonal causes causes of vulvodynia
(and other types of female sexual dysfunction)
Even rodents choose different partners when they are treated with an anti-androgen!!

Other potential causes of a "hormonally mediated vestibulodynia"
Spironolactone
GNRH agonists
Tamoxifen
Aromitase inhibitors
Depo-Provera
oophorectomy
premature ovarian failure
MENOPAUSE (but we instead call it "vulvovaginal atrophy" or "atrophic vaginitis" or "Genitourinary Syndrome of Menopause")
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